名古屋大学博士学位論文 学位の種類 : 博士(医学)(論文) 学位授与年月日:平成5年2月19日 竹中晃氏の博士論文として提出された

The purpose of the present study was to explore the relationship between internalized racism, stereotype threat, self-handicapping, test performance, and cardiovascular responses in Black individuals. Stereotype threat, or apprehension about confirming a negative stereotype, has been shown to lead to self-handicapping, poor academic performance, as well as increased cardiovascular reactivity. Internalized racism, or the acceptance of negative stereotypes about one's group, is a factor that may moderate these relationships. One-hundred nine (84% female, 16% male) Black undergraduates participated in a laboratory study. Half of the participants were put in a stereotype-threatened condition and the other half were in a neutral condition. The participants were permitted unlimited time in which to practice for a verbal test and then were tested on their verbal ability while their blood pressure was monitored. Results indicated that internalized racism moderates the relationship between stereotype threat and systolic blood pressure, but not diastolic blood pressure or heart rate. However, the moderating effect of internalized racism in the relationship between stereotype threat and self-handicapping or test performance was not significant. It seems that individuals who do not accept the negative stereotypes about Blacks as a group experienced increased systolic blood pressure responses in stereotype-threatened situations compared to Black individuals who do accept the negative stereotypes. The implication is that Black individuals who challenge negative stereotypes will feel more stress when placed in situations where they are at risk of confirming those negative stereotypes. This study provides insight into reasons for the variability of cardiovascular disease among Black Americans, who typically experience a higher incidence overall compared to other ethnic groups.

Hintergrund: Bei etwa der Hälfte aller Patienten mit Herzinsuffizienz kann die Symptomatik auf eine Herzinsuffizienz bei erhaltener Ejektionsfraktion (HFPEF) zurückgeführt werden. Lange Zeit wurde der Herzinsuffizienz bei erhaltener Ejektionsfraktion eine bessere Prognose nachgesagt als der systolischen Herzinsuffizienz. Neuere Untersuchungen zeigen allerdings, dass die Prognose vergleichbar schlecht und gegenüber der Allgemeinbevölkerung deutlich herabgesetzt ist. Trotz großer klinischer Relevanz gibt es weder eine allgemeingültige Leitlinie zur Diagnostik der HFPEF noch eine überzeugende Therapie, die Morbidität und Mortalität reduziert. Auch ist bislang nicht geklärt, inwieweit sich demographische und klinische Faktoren auf die den Empfehlungen zugrunde liegenden Zielparameter auswirken. Ebenfalls ungeklärt ist, ob und wie diese krankheitstypischen, für die Diagnose wegweisenden Schlüsselparameter wie Leistungsfähigkeit, diastolische Funktion, neurohumorale Aktivierung und linksatriales und linksventrikuläres Remodeling auch unabhängig von demographischen und klinischen Faktoren untereinander assoziiert sind. Dieses ist von großem Interesse, da man die Parameter, anhand derer man eine Krankheit diagnostizieren und den Effekt einer Therapie messen will, gut kennen sollte und die Einflüsse, denen sie unterliegen, bekannt sein sollten. Material und Methoden: In der vorliegenden Arbeit werden Baselinedaten der Aldo-DHF-Studie präsentiert, die 422 ambulante Patienten mit einer symptomatischen Herzinsuffizienz bei erhaltener Ejektionsfraktion einschloss (mittleres Alter 67 Jahre, 48% männlich). Anhand dieser Daten wurden die Zusammenhänge zwischen zahlreichen demographischen und klinischen Charakteristika und Werten der Leistungsfähigkeit (peak VO 2), Werten der diastolischen Dysfunktion ( E/e‘), Höhe der neurohumoralen Aktivität (NT-proBNP) und Werten des kardialen Remodelings (linksatrialer Volumenindex und linksventrikulärer Massenindex) ermittelt sowie ihre Assoziation untereinander geprüft. Dazu wurden die Patienten nach ihrem jeweiligen NYHA-Stadium in zwei Gruppen unterteilt (NYHA-Stadium II, n= 363 Patienten; NYHA-Stadium III, n= 59 Patienten). Beziehungen zwischen Basischarakteristika und dem jeweiligen Zielparameter wurden zunächst mit einfacher Regression und anschließend mit multipler Regression untersucht. Beziehungen der Zielparameter untereinander wurden zum einen durch den Pearson-Korrelationskoeffizienten 5 Zusammenfassung 61 und zum anderen nach Adjustierung durch einen partiellen Korrelationskoeffizienten dargestellt. Ergebnisse: Wir stellten fest, dass das Alter der einzige Faktor ist, der sich auch unabhängig von demographischen und klinischen Faktoren signifikant negativ auf alle fünf untersuchten Schlüsselparameter auswirkt: die peak VO2 (p= < 0.001), das E/e‘ (p= 0,009), das NT-proBNP (p= < 0.001), den LAVI (p= 0.003) und den LVMI (p= 0.02). Die Leistungsfähigkeit (peak VO2) wird negativ durch ein weibliches Geschlecht (p= <0.001), chronotrope Inkompetenz (p= 0.002) und einzelne Begleiterkrankungen wie KHK (p= 0.002), DM (p= 0.05) und das Schlafapnoe-Syndrom(p= 0.02) beeinflusst. Außerdem wird die diastolische Funktion (E/e‘) durch weibliches Geschlecht (p= 0.008), durch einen höheren Pulsdruck (p= 0.04), eine niedrigere Ruheherzfrequenz (p= 0.03) und die Behandlung mit Betablockern (p= 0.001) herabgesetzt. Bei der Untersuchung des Zusammenhangs von Charakteristika des Patientenkollektivs und der neurohumoralen Aktivität zeigte sich, dass ein höherer BMI (p= 0.03) mit einem niedrigeren NT-proBNP-Spiegel assoziiert ist. Vorhofflimmern (p= < 0.001), eine niedrige Ruheherzfrequenz (p= 0.05), chronotrope Inkompetenz (p= 0.02), eine schlechte Nierenfunktion (p= 0.05), niedrige Hämoglobinspiegel (p= < 0.001), die Einnahme von Diuretika (p= 0.05) und Betablockern (p= < 0.001) sind hingegen mit einem erhöhten NT-proBNP-Spiegel assoziiert. Obgleich signifikant, korrelieren die peak VO2, E/e‘ und NT-proBNP unadjustiert lediglich moderat miteinander, während LAVI und LVMI gar nicht mit der Leistungsfähigkeit assoziiert sind. Nach Adjustierung entfällt die Signifikanz des zuvor genannten Zusammenhangs von peak VO2 mit E/e‘ und NT-proBNP. Das bedeutet, dass die Leistungsfähigkeit mit keinem der anderen Schüsselparameter in Zusammenhang steht, wenn man sie unabhängig von demographischen und anderen klinischen Faktoren betrachtet. Der Zusammenhang von E/e‘, NT-proBNP und LAVI sowie LVMI und LAVI bleibt auch nach Adjustierung bestehen. Patienten mit einem entsprechend den vorgegebenen Grenzwerten niedrigen NT-proBNP-Spiegel (NT-proBNP ≤ 220 ng/l) und niedrigen E/e‘-Werten (E/e‘ ≤ 15) hatten signifikant bessere peak VO2- und AT VO2-Werte als Patienten, bei denen auch nur einer dieser beiden Werte erhöht war. Schlussfolgerung: Wir untersuchten, welche demographischen und klinischen Faktoren mit der körperlichen Leistungsfähigkeit, der diastolischen Funktion, der neurohumoralen 5 Zusammenfassung 62 Aktivierung und dem linksatrialen sowie linksventrikulären Remodeling bei Patienten mit Herzinsuffizienz und erhaltener systolischer Funktion assoziiert sind. Besonders interessant war, dass die maximale Leistungsfähigkeit mit keinem der anderen diagnostischen Schlüsselparameter, unabhängig von demographischen und klinischen Faktoren, in Zusammenhang steht. Dennoch scheinen empfohlene Grenzwerte bei NT-proBNP und E/e‘ zur Diagnose einer HFPEF sinnvoll, da sie grundsätzlich Patienten mit einer niedrigeren peak VO2 selektieren. Die Herzinsuffizienz mit erhaltener EF ist ein multifaktoriell beeinflusstes klinisches Syndrom. Da die eingeschränkte Leistungsfähigkeit nicht unabhängig von anderen Faktoren mit den diagnostischen Parametern assoziiert ist, ist die individuelle Bewertung von Faktoren, die zu den Symptomen der Patienten beitragen, obligatorisch für die klinische Beurteilung und Therapie bei Patienten mit HFPEF.

No description available.

Speckle tracking echocardiography (STE) is a relatively new imaging modality that enables the direct measurement of active contractile myocardial tissue in an offline analysis. This is accomplished through a software algorithm that tracks collections of acoustic markers, known as 'speckles', that are unique to a given section of myocardium. By measuring the displacement of these 'speckles' as the heart contracts and relaxes, STE produces parameters of the strain, or percent change in length, exhibited by the myocardium. As multiple studies have shown, this strain data produced by tracking of the global left atrium has the ability to accurately assess the physiologic functions of the atrium as a reservoir, conduit and booster pump in the cardiac cycle. Despite these valuable correlations, there are noted problems with STE regarding acoustic cluttering and disappearance of 'speckles' that can occur as the selected region of interest moves out of the field of view or becomes obscured. These problems may be increased when tracking an extended region of myocardium. Therefore, this present study sought to test a new method of assessing left atrial function with STE strain analysis by focusing on a concise region of the atrium, specifically the interatrial septum. To test this, the echocardiograms of 37 patients were obtained and grouped according to the designation of their cardiac function as normal (n=11), abnormal (n=12), or exhibiting signs of cardiac amyloidosis (n=14). In all patients, STE strain analysis was performed on the both the global left atrium and the interatrial septum. Measurements of the mean peak strain observed in the resultant strain curves were recorded for both STE scans of each patient. The curves produced by the tracking the segments of the entire atrium (6 segments) and interatrial septum (3 segments) were compared based on the exhibited changes in strain seen in the relative shapes of the curves, as well as the spread of the segmental strain curves about the calculated mean strain curve. Additionally, the number of segments that were either unsuccessfully or incorrectly tracked was recorded as a measure of the accuracy of STE. As a final step, the interatrial strain curves of four selected patients in the various states of ventricular diastolic dysfunction were chosen and compared with data obtained from scans of mitral flow echocardiography and tissue Doppler imaging (TDI) in an attempt to correlate the exhibited changes in strain shown in the interatrial septum with the physiologic functions of the atrium during ventricular diastole. The results showed that the mean peak strain of the global atrial strain trace decreased from normal (41.32%±10.8) to abnormal (21.69%±13.8) to the amyloid group (10.41%±6.9). This trend was echoed in the mean peak strain measured in the interatrial septum, as measured in normal (64.2%±15.6), abnormal (28.37%±13.4) and amyloid groups (12.21%±12.1). When the strain curves of the entire atrium and interatrial septum were compared, they demonstrated similar patterns in the timing of changes in strain, however the strain curves of the individual interatrial septum segments showed a much more concise grouping about the mean strain curve and were less likely to exhibit discordant segmental strain curves that deviated from the pattern established by all other segments in the trace. Additionally, within the STE scans of the global atrium, the interatrial septum exhibited a higher percentage of successfully tracked segments than did the lateral atrial wall; this trend was universally exhibited in all three groups. Finally, the interatrial septum strain curves, mitral flow echocardiography and TDI scans all demonstrated similar indications of left atrial function in the four selected patients. Ultimately, STE strain analysis of the interatrial septum appears to be a more accurate method of tracking the atrial myocardium than STE tracing of the global left atrium. Furthermore, it shows viable potential as a method for assessing the global physiologic function of the left atrium, as indicated by the similarities between the trends exhibited by these STE scans and the data gathered from scans produced by mitral flow echocardiography and TDI.

O Câncer de mama é um dos problemas de saúde pública mais importantes em nosso país. São estimados, para 2010, 49.400 novos casos de câncer de mama no Brasil, com um risco estimado de 51 casos a cada 100 mil mulheres. A estratégia de tratamento das pacientes com tumores de mama pode passar pelo uso de quimioterapia. A doxorrubicina é uma das drogas mais ativas para o câncer de mama, pertencendo ao grupo das antraciclinas. A família das antraciclinas apresenta como efeito colateral dano ao miocárdio que pode chegar a 36% dependendo da dose utilizada. O efeito sobre o miocárdio costuma ocorrer mais comumente durante ou logo após o último ciclo de quimioterapia podendo, entretanto ocorrer após vários anos do último ciclo de quimioterapia. O objetivo deste estudo foi analisar as alterações da função diastólica ventricular esquerda em mulheres usuárias de antraciclínicos no tratamento do câncer de mama. Realizamos um estudo prospectivo, em uma coorte de mulheres entre 18 e 69 anos, com câncer de mama e indicação de quimioterapia com doxorrubicina. Acompanhamos por período não inferior a 18 meses um grupo de 38 pacientes que cumpriram os critérios de elegibilidade. A dose de doxorrubicina utilizada variou de 50 a 60 mg/m/SC. Todos os pacientes são do sexo feminino, e portadores do tipo histológico carcinoma ductal infiltrante. Duas pacientes faleceram durante o estudo, de causa não cardíaca. Em nossa avaliação, ao final do estudo observamos que os parâmetros: dimensões do átrio esquerdo, dimensões do ventrículo esquerdo na diástole, dimensões do ventrículo esquerdo na sístole, velocidade da onda E, relação da fase de enchimento rápido pela sístole atrial, velocidade diastólica tardia do anel mitral, velocidade diastólica precoce do anel mitral, tempo de desaceleração e a relação da velocidade de enchimento rápido precoce de VE pela velocidade diastólica precoce do anel mitral demonstraram serem parâmetros de grande utilidade para seguimento da lesão cardíaca por antraciclínicos. Já o que não ocorreu com: a fração de encurtamento, fração de ejeção, volume do AE, volume do AE corrigido pela superfície corporal, velocidade diastólica tardia, tempo de relaxamento isovolumétrico, velocidade sistólica do anel mitral, que não apresentaram alterações significativas neste estudo. A análise da função diastólica utilizando o ecocardiograma mostrou ser um método eficaz, que em conjunto com a da função sistólica possibilita detectar precocemente o possível dano miocárdico, oriundo ao uso da quimioterapia com antraciclínicos, favorecendo uma intervenção terapêutica precoce e adequada. / Breast cancer is one of the most important public health of our country. It was estimated for 2010, 49,400 new cases of breast cancer in Brazil, with an estimated risk of 51 cases per 100 000 women. The treatment strategy of patients with breast tumors can pass through the use of chemotherapy. Doxorubicin is one of the most active drugs for breast cancer, belonging to the group of anthracyclines. The family of anthracyclines has as side effect myocardial damage that can reach 36% depending on the dose used. The effect on the myocardium is known to occur most commonly during or shortly after the last cycle of chemotherapy, but it could occur several years after the last cycle of chemotherapy. The objective of this study was to evaluate changes in left ventricular diastolic function in women users of anthracyclines in the treatment of breast cancer. A prospective study in a cohort of women aged 18 to 69 years, with breast cancer and indications for chemotherapy with doxorubicin. We follow a period of not less than 18 months a group of 38 patients who met the eligibility criteria. The doxorubicin dose used ranged from 50 to 60 mg / m / SC. All patients were female, and carriers of infiltrating ductal carcinoma histology. Two patients died during the study of noncardiac causes. In our view, the end of the study showed that the parameters: size of left atrium (LA), left ventricular (LV) dimensions in diastole, left ventricular dimensions in systole, E wave velocity, ratio of phase rapid filling by atrial systole, late diastolic velocity of mitral annulus, early diastolic velocity of mitral annulus, deceleration time and speed ratio early rapid filling of the LV early diastolic velocity of mitral annulus proved to be useful parameters for monitoring of cardiac injury by anthracyclines. Although this did not occur with: fractional shortening, ejection fraction, LA volume, LA volume corrected for body surface area, late diastolic velocity, isovolumetric relaxation time, mitral annular systolic velocity, which showed no significant changes in this study. The analysis of diastolic function using echocardiography proved to be an effective method, which, together with the systolic function allows early detection of possible myocardial damage, arising the use of chemotherapy with anthracycline, favoring an early and appropriate therapeutic intervention.

O Câncer de mama é um dos problemas de saúde pública mais importantes em nosso país. São estimados, para 2010, 49.400 novos casos de câncer de mama no Brasil, com um risco estimado de 51 casos a cada 100 mil mulheres. A estratégia de tratamento das pacientes com tumores de mama pode passar pelo uso de quimioterapia. A doxorrubicina é uma das drogas mais ativas para o câncer de mama, pertencendo ao grupo das antraciclinas. A família das antraciclinas apresenta como efeito colateral dano ao miocárdio que pode chegar a 36% dependendo da dose utilizada. O efeito sobre o miocárdio costuma ocorrer mais comumente durante ou logo após o último ciclo de quimioterapia podendo, entretanto ocorrer após vários anos do último ciclo de quimioterapia. O objetivo deste estudo foi analisar as alterações da função diastólica ventricular esquerda em mulheres usuárias de antraciclínicos no tratamento do câncer de mama. Realizamos um estudo prospectivo, em uma coorte de mulheres entre 18 e 69 anos, com câncer de mama e indicação de quimioterapia com doxorrubicina. Acompanhamos por período não inferior a 18 meses um grupo de 38 pacientes que cumpriram os critérios de elegibilidade. A dose de doxorrubicina utilizada variou de 50 a 60 mg/m/SC. Todos os pacientes são do sexo feminino, e portadores do tipo histológico carcinoma ductal infiltrante. Duas pacientes faleceram durante o estudo, de causa não cardíaca. Em nossa avaliação, ao final do estudo observamos que os parâmetros: dimensões do átrio esquerdo, dimensões do ventrículo esquerdo na diástole, dimensões do ventrículo esquerdo na sístole, velocidade da onda E, relação da fase de enchimento rápido pela sístole atrial, velocidade diastólica tardia do anel mitral, velocidade diastólica precoce do anel mitral, tempo de desaceleração e a relação da velocidade de enchimento rápido precoce de VE pela velocidade diastólica precoce do anel mitral demonstraram serem parâmetros de grande utilidade para seguimento da lesão cardíaca por antraciclínicos. Já o que não ocorreu com: a fração de encurtamento, fração de ejeção, volume do AE, volume do AE corrigido pela superfície corporal, velocidade diastólica tardia, tempo de relaxamento isovolumétrico, velocidade sistólica do anel mitral, que não apresentaram alterações significativas neste estudo. A análise da função diastólica utilizando o ecocardiograma mostrou ser um método eficaz, que em conjunto com a da função sistólica possibilita detectar precocemente o possível dano miocárdico, oriundo ao uso da quimioterapia com antraciclínicos, favorecendo uma intervenção terapêutica precoce e adequada. / Breast cancer is one of the most important public health of our country. It was estimated for 2010, 49,400 new cases of breast cancer in Brazil, with an estimated risk of 51 cases per 100 000 women. The treatment strategy of patients with breast tumors can pass through the use of chemotherapy. Doxorubicin is one of the most active drugs for breast cancer, belonging to the group of anthracyclines. The family of anthracyclines has as side effect myocardial damage that can reach 36% depending on the dose used. The effect on the myocardium is known to occur most commonly during or shortly after the last cycle of chemotherapy, but it could occur several years after the last cycle of chemotherapy. The objective of this study was to evaluate changes in left ventricular diastolic function in women users of anthracyclines in the treatment of breast cancer. A prospective study in a cohort of women aged 18 to 69 years, with breast cancer and indications for chemotherapy with doxorubicin. We follow a period of not less than 18 months a group of 38 patients who met the eligibility criteria. The doxorubicin dose used ranged from 50 to 60 mg / m / SC. All patients were female, and carriers of infiltrating ductal carcinoma histology. Two patients died during the study of noncardiac causes. In our view, the end of the study showed that the parameters: size of left atrium (LA), left ventricular (LV) dimensions in diastole, left ventricular dimensions in systole, E wave velocity, ratio of phase rapid filling by atrial systole, late diastolic velocity of mitral annulus, early diastolic velocity of mitral annulus, deceleration time and speed ratio early rapid filling of the LV early diastolic velocity of mitral annulus proved to be useful parameters for monitoring of cardiac injury by anthracyclines. Although this did not occur with: fractional shortening, ejection fraction, LA volume, LA volume corrected for body surface area, late diastolic velocity, isovolumetric relaxation time, mitral annular systolic velocity, which showed no significant changes in this study. The analysis of diastolic function using echocardiography proved to be an effective method, which, together with the systolic function allows early detection of possible myocardial damage, arising the use of chemotherapy with anthracycline, favoring an early and appropriate therapeutic intervention.

Em pacientes com insuficiência cardíaca crônica podemos observar um aumento da atividade inflamatória, caracterizada por aumento de proteínas de fase ativa, citocinas circulantes e ativação de células do sistema imune. É descrito também que o exercício físico beneficia esses pacientes, porém ainda não está claro se esse benefício ocorre através da modulação do processo inflamatório no sistema cardiovascular. Assim, o objetivo deste estudo foi investigar, em pacientes com insuficiência cardíaca, o efeito do treinamento físico sobre a disfunção ventricular, avaliada pelo quadro clínico e ecocardiograma, e sobre vias de sinalização envolvidas no processo inflamatório cardiovascular, como CD40/CD40L, IL-6, TNF-alfa e PPARs. Foram selecionados dezoito pacientes com diagnóstico de IC, todos classificados com classe funcional II, com idade 57,17±2,9 anos. Os pacientes foram randomizados em dois grupos: grupo controle, que permaneceu sedentário e grupo treino, onde os pacientes foram treinados três vezes por semana, em cicloergômetro, durante 60 minutos por quatro meses. Os marcadores inflamatórios plasmáticos, CD40L, IL-6, TNF-alfa foram dosados por ELISA e a expressão de mRNA de CD40 e PPARs alfa e y em leucócitos circulantes pela técnica de RT-PCR. A função cardíaca foi avaliada pelo ecocardiograma, e a capacidade funcional foi avaliada através da ergoespirometria. Os pacientes submetidos ao treinamento físico apresentaram significante aumento do VO2 , comparados ao grupo controle (17,52±1,47 vs 21,14±0,86, respectivamente; p<0,05). Também foi observada melhora da função ventricular diastólica e manutenção da fração de ejeção do ventrículo esquerdo, que piorou nos pacientes mantidos sedentários (controle (38,00±3,37 vs 36,44±3,38, respectivamente; p<0,05). Em relação às vias de sinalização inflamatórias, não houve diferença em nenhum dos marcadores estudados (níveis plasmáticos de IL-6, TNF-alfa e CD40L e na expressão de mRNA de CD40 e PPARs alfa e y em leucócitos circulantes) quando comparados o grupo treinado ao controle. Conclui-se que o treinamento físico é efetivo na melhora da capacidade funcional e função cardíaca e que a atividade inflamatória característica nesses pacientes não está associada com essas mudanças. / Patients with chronic heart failure present increased inflammatory activity, characterized by high levels of active phase proteins and cytokines, as well as activated immune cells. Physical training is reported to be beneficial for these patients, however, it is not clear whether this benefit occurs thorough modulation of the inflammatory process that the cardiovascular system. Therefore, the main objective of this study was to investigate, in patients with chronic heart failure, the effect of physical training on ventricular dysfunction, assessed by clinical exam and echocardiography, as well as on signaling pathways involved in the cardiovascular inflammatory process, like CD40/CD40L, IL-6, TNF and PPARs. Eighteen patients diagnosed with chronic heart failure, functional class II, were selected (age=57,17±2,9). They were randomly divided in two groups: a control group and a trained group, whose patients were submitted to physical training for 4 months, 3 times/week, for 60 min, in a cycle ergometer. Plasmatic cytokines and CD40L were measured by ELISA; mRNA for CD40 and PPARs alfa / y were measured by RT-PCR in circulating leukocytes. Cardiac function was evaluated by echocardiography and functional capacity by ergospirometry. Patients submitted to physical training presented a significant increase in VO2 , compared to control group (17,52±1,47 vs 21,14±0,86 , respectively; p<0,05). Improvement in diastolic ventricular function was also observed , as well as maintenance of left ventricular ejection fraction , that was impaired in patients in the control group (38,00±3,37 vs 36,44±3,38, respectively; p<0,05). Regarding the inflammatory signaling pathways, no difference was observed in any of the markers evaluated (plasmatic levels of IL6, TNF, CD40L and expression of mRNA for CD40 and PPARs alfa / y in circulating leukocytes). Therefore, we can conclude that physical training is effective in improving functional capacity and cardiac function in patients with chronic failure; this phenomenon is unlikely to be related to modulation of inflammatory signaling pathways characteristic of cardiovascular diseases.

Orientador: Otavio Rizzi Coelho / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-11T03:33:19Z (GMT). No. of bitstreams: 1 Marsaro_EliandraAparecida_D.pdf: 2012256 bytes, checksum: 4f444be0b390a7068513571b25f2a026 (MD5) Previous issue date: 2008 / Resumo: Introdução: Estudos têm sugerido que as estatinas aumentam a sobrevida em pacientes portadores de insuficiência cardíaca com função sistólica preservada, benefício provavelmente atribuído aos seus efeitos pleiotrópicos em co-morbidades como doença arterial coronariana e hipertrofia de ventrículo esquerdo. Objetivos: avaliar se o uso de sinvastatina em dose máxima por um período de 6 meses pode alterar parâmetros ecoDopplercardiográficos de função diastólica em pacientes hipertensos com disfunção diastólica isolada. Pacientes e Métodos: Este é um estudo aleatorizado duplo-cego placebo controlado. Foram estudados 30 indivíduos hipertensos normocolesterolêmicos com idade = 50 anos sem evidência de hipertrofia de ventrículo esquerdo ou isquemia miocárdica investigada por ecocardiografia de estresse. Os pacientes foram aleatorizados para placebo ou sinvastatina (80mg) e reavaliados após 6 meses. Resultados: Os grupos Sinvastatina e Placebo apresentavam características semelhantes no início do estudo. Após 6 meses de acompanhamento, 67% dos pacientes do grupo Sinvastatina apresentaram normalização da função diastólica contra 33% do grupo Placebo (p<0.05). Todos os indivíduos tratados com sinvastatina que não apresentaram normalização da função diastólica tiveram aumentos da pressão arterial sistólica e diastólica após os 6 meses (p<0.05 para ambas). Conclusão: O tratamento de hipertensos com sinvastatina 80mg/d por 6 meses foi associado a uma maior taxa de normalização da função diastólica quando comparado a placebo. O aumento da pressão arterial observado em alguns indivíduos aparentemente aboliu esse benefício / Abstract: Background: Therapy with statins was suggested to improve survival on heart failure with preserved systolic function. This benefit was attributed probably to their pleiotropic effects on co-morbidities like coronary heart disease or left ventricular hypertrophy. Aims: evaluate the impact of the treatment with simvastatin on echocardiografic parameters of diastolic function in hypertensive patients without coronary heart disease or left ventricular hypertrophy. Patients and methods: This is a randomized, placebo-controlled, double-blind study. We studied 30 normocholesterolemic hypertensive patients = 50 years without evidence of left ventricular hypertrophy or coronary artery disease assessed under rest and stress echocardiography. The patients have been randomized for placebo or simvastatin (80mg) and reevaluated after 6 months. Results: The baseline characteristics were similar between groups. After six months of treatment, 67% of the patients of simvastatin group presented normalization of diastolic function against 33% in the placebo group (p<0.05). All subjects in simvastatin group who not presented normalization of the diastolic function have increased on systolic and diastolic blood pressure after 6 months (p<0.05 for both). Conclusion: This study demonstrates that a 6 months therapy with simvastatin 80mg/d in asymptomatics hypertensive subjects with diastolic dysfunction had a higher rate of normalization of diastolic function than placebo. The increased of blood pressure observed in some subjects in the simvastatin group appearentelly abolished this benefit / Doutorado / Clinica Medica / Mestre em Clinica Medica

O +dP/dt e o dP/dt são considerados índices ecocardiográficos de avaliação da função sistólica e diastólica, respectivamente, menos influenciados pela pré e pós-carga do que os índices calculados na fase de ejeção. O objetivo desse estudo foi determinar se o dP/dt não-invasivo se correlaciona com os índices ecocardiográficos sistólicos e diastólicos e se pode ser usado para identificar animais com e sem remodelamento, aqueles com e sem ICC e avaliar a gravidade da DVCM. Esta pesquisa constituiu um estudo clínico observacional prospectivo transversal, realizada em cães com DVCM. Comparou-se o +dP/dt e o dP/dt entre grupos divididos quanto à presença de remodelamento e presença ou não de ICC; para a comparação do dP/dt em relação à função diastólica do VE, os cães foram distribuídos de acordo com o padrão diastólico. Os cães foram submetidos ao exame ecodopplercardiográfico para mensuração do +dP/dt, -dP/dt e dos demais índices ecocardiográficos. Foram inclusos ao todo 57 cães com DVCM, em estágios B1 (n=13), B2 (n=18) e C+D (n=26). Comparando-se o +dP/dt nos três grupos divididos de acordo com à presença de remodelamento, com ou sem ICC, o grupo C+D (2142 mmHg/s, P25-P75 = 2023-2456) apresentou +dP/dt significativamente mais baixo que o grupo B1 (2865 mmHg/s, P25-P75 = 2383-3308) e B2 (2721 mmHg/s, P25-P75 = 2241-3186) (P = 0,0023). O mesmo foi observado para o dP/dt, quando comparado o grupo C+D ao grupo B1 (968,5 mmHg/s ± 266,8 e 1198 mmHg/s ± 165,7; P= 0,0115). Quando o dP/dt foi comparado entre os grupos com ICC e sem ICC, o grupo com ICC apresentou valores menores tanto do +dP/dt (2142 mmHg/s, P25-P75 = 2023-2456; 2858 mmHg/s, P25-P75 = 2299-3241; P = 0,0007) como do dP/dt (968,5 ± 266,8 mmHg/s e 1155 mmHg/s ± 199,0; P = 0,0041). Quanto à função diastólica, o grupo com padrão restritivo (769,7 mmHg/s ± 124,1) apresentou valores menores do -dP/dt quando comparados aos grupos sem disfunção diastólica (1132 mmHg ± 204,0), alteração de relaxamento (1229 mmHg ±186,9) e padrão pseudonormal (1107 mmHg ±223,4) (P&lt; 0,0001). Utilizando-se +dP/dt&lt;1800 mmHg/s como ponto de corte, houve duas vezes mais chance do cão com DVCM ter ICC do que não ter. Considerando-se como ponto de corte um -dP/dt&lt;800mmHg/s, a chance de ter ICC é oito vezes maior do que não ter e a chance de ter padrão diastólico restritivo é oito vezes maior do que não ter. Conclui-se que o +dP/dt e o dP/dt não-invasivos podem contribuir, respectivamente, para a avaliação da função sistólica e diastólica. / Noninvasive +dP/dt and dP/dt derived from mitral regurgitant jet are considered echocardiographic indexes for assessment of systolic and diastolic function respectively, that have less preload and afterload dependence than the ejection phase indexes. This study aimed to determine whether non-invasive dP/dt correlates with other systolic and diastolic echocardiographic indexes, and if they can be used to identify dogs with and without remodeling, with or without congestive heart failure (CHF) and for evaluation of chronic mitral valve disease (CMVD) severity. An observational prospective cross-sectional clinical study was undertaken including dogs with CMVD. Dogs were distributed in groups regarding the presence of remodeling and heart failure,to evaluate +dP/dt and dP/dt, and distributed according the diastolic pattern to compare dP/dt regarding diastolic function. Echocardiographic exam was obtained for conventional indexes and to measure +dP/dt and -dP/dt. Fifty seven dogs diagnosed with CMVD and classified according to the stages [B1 (n=13), B2 (n=18), C+D (n=26)] were included. In the comparison among the three groups regarding the presence of remodeling and CHF, group C+D (2142 mmHg/s, P25-P75 = 2023-2456) had +dP/dt significantly lower than B1 (2865 mmHg/s, P25-P75 = 2383-3308) and B2 (2721 mmHg/s, P25-P75 = 2241-3186) (P = 0.0023). Group C+D also had lower dP/dt, compared to B1 (968.5 mmHg/s ± 266.8 and 1198 mmHg/s ± 165.7; P= 0.0115). Group of dogs with CHF compared to those without CHF, showed lower +dP/dt (2142 mmHg/s, P25-P75 = 2023-2456; 2858 mmHg/s, P25-P75 = 2299-3241; P = 0.0007) as well as dP/dt (968.5 ± 266.8 mmHg/s e 1155 mmHg/s ± 199.0; P=0.0041). Regarding diastolic function, -dP/dt was lower for the restrictive pattern group (769.7 mmHg/s ± 124.1) compared to those without diastolic disfunction, (1132 mmHg ± 204.0), relaxation abnormality (1229 mmHg ±186.9) and pseudonormal pattern (1107 mmHg ±223.4) (P&lt; 0.0001). Considering +dP/dt&lt1800 mmHg/s as cutoff value, there is twice the chance for the dog with CMVD to have CHF than not to have. With a -dP/dt&lt;800mmHg/s as a cut off value, the chance of having CHF is eigth times higher than not having it. It is concluded that non-invasive doppler derived +dP/dt and dP/dt may contribute respectively, for systolic and diastolic assessment of dogs with CMVD.