Trata-se de um estudo descritivo, retrospectivo, com abordagem quantitativa cujo objetivo geral foi descrever e analisar o perfil epidemiológico dos pacientes com Insuficiência Cardíaca atendidos pela Clinica de IC de um Hospital Universitário. Os objetivos específicos orientam-se para:(a)Caracterizar os casos de Insuficiência Cardíaca segundo variáveis demográficas, variáveis clínicas, de diagnóstico e co morbidades;(b)Comparar as características clínicas e demográficas dos pacientes conforme grupos etiológicos identificados e fração de ejeção;(c)Determinar a taxa de mortalidade e hospitalização dos pacientes acompanhados pela clínica. Os dados analisados neste estudo são oriundos de um banco de dados onde são alocadas informações dos pacientes em atendimento ambulatorial da referida clinica.Para a análise dos dados foi utilizada a estatística descritiva, freqüências e porcentagens assim como tabelas e gráficos para a demonstração dos dados levantados.Os mesmos foram analisados através do software SPSS v.18.0, no qual se utilizou a estatística multivariada e curvas de sobrevida de Kaplan-Meyer.Os resultados apontam para uma predominância masculina de 60,1%, com idade de 63,5 anos. Na caracterização quanto à classe funcional observa-se que a predominante é a classe funcional I e II com 73,6% do total. Os pacientes assistidos apresentam uma média de 42% da fração de ejeção do ventrículo esquerdo e 61,7% possuem etiologia não isquêmica. Em nosso estudo, descrevemos 71,8% de portadores de disfunção sistólica. Os pacientes com etiologia isquêmica tinham predomínio do sexo masculino(70,7%), e a etiologia não isquêmica com uma prevalência maior do sexo feminino(45,5%vs 29,3%;p<0,001). Além disso, os pacientes isquêmicos eram mais idosos (p<0,001), com historia familiar de DAC(p<0,041), presença de diabetes (p<0,001). A disfunção sistólica(FE<50%) era predominante no grupo de pacientes isquêmicos(77%vs 69%; p=0,048).As classes funcionais mais avançadas(III e IV) foram menos predominantes nos indivíduos isquêmicos(32,5%) em relação aos não isquêmicos(41,3%;p=0,041).O paciente de etiologia isquêmica recebeu tratamento farmacológico semelhante ao não isquêmico com exceção do uso de AAS(p<0,001).Esses indivíduos cursaram com maior numero de internações por outras causas exceto IC(p<0,001) e maior numero de óbitos(p=0,007).Em relação à fração de ejeção, observou-se que indivíduos com FE>50% tinham predomínio do sexo feminino(p=0,006),mais idosos(p<0,001),de etiologia não isquêmica(p=0,048) e classes funcionais I e II(p=0,025).Indivíduos com FE<50% eram mais graves, apresentando maior número de internações por IC(37,8%vs20%;p<0,001), e internações por outras causas(27,2%vs17,5%;p=0,018) e maior número de óbitos (18%vs8,4%;p=0,005) do que os com fração de ejeção preservada. O resultado desse estudo teve como finalidade o conhecimento do perfil de uma população própria, com o objetivo de aprimorar a assistência prestada a ela. Os enfermeiros de Clínicas de IC, juntos com os profissionais da equipe multidisciplinar, desempenham papel fundamental no acompanhamento, orientação e educação desses pacientes. / It is a descriptive, retrospective, study with quantitative approach whose general objective was to describe and analyze the epidemiological profile of patients with heart failure treated in a heart failure clinic of a university hospital. The specific objectives are oriented to a) characterize the cases of heart failure according to demographic variables, clinical variables, diagnosis and comorbidities, (b) compare clinical and demographic characteristics of patients according to the main groups identified and etiologic fraction ejection, (c) Determine mortality and hospitalization rates of patients followed by the HF clinic. The data analyzed in this study come from a database which is allocated information of ambulatory patients referred to the clinic. For data analysis was used descriptive statistics with mean, median and standard deviation, frequencies and percentages ,tables and graphs to demonstrate the data collected as well multivariate statistical analysis and Kaplan-Meyers survival curves. They were analyzed using the software SPSS v.18.0. The results indicate a male predominance of 60.1% with an average age of 63.5 years. The functional class observed that was the predominant class I and II, 73.6% of the total. Patients have attended an average of 42% ejection fraction of left ventricle and 61.7% had non ischemic etiology. In our study, we describe 71.8% of patients with systolic dysfunction. Patients with ischemic etiology were predominantly male (70.7%), and non ischemic etiology with a higher prevalence of females (45.5% vs 29.3%, p<0.001). In addition, ischemic patients were older (p<0.001), family history of CAD (p<0.041), diabetes (p<0.001). Systolic dysfunction (EF<50%) was predominant in the group of ischemic patients (77% vs 69%, p=0.048).The more advanced functional class (III and IV) were less prevalent in ischemic subjects(32.5%) compared to non-ischemic (41.3%) (p=0.041). Patients with an ischemic etiology had highest number of hospitalizations for other causes than HF (p<0.001) and greater number of deaths (p=0.007). Regarding the ejection fraction was observed that individuals with EF > 50% were predominantly female (p=0.006), older (p<0.001), non-ischemic etiology (p=0.048) and functional classes I and II (p=0.025). Individuals with EF <50% were more severe, with higher number of hospitalizations for HF (37.8% vs 20%) (p<0.001), and hospitalizations due to other causes (27.2% vs 17.5%) (p=0.018) and higher number of deaths (18% vs 8.4%) (p=0.005) than those with preserved ejection fraction. The results of this study were aimed at the knowledge of the real profile of a population with distinct characteristics, in order to improve the care given to it. The nurses in HF clinics with other professionals in the multidisciplinary team, play a key role in monitoring, guidance and education of these patients.

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Agradecemos a compreensão. on 2018-04-05T19:38:24Z (GMT) / Submitted by Francini Piccolo Ferreira null (francini.estatistica@gmail.com) on 2018-04-06T17:15:12Z No. of bitstreams: 1 Dissertação Francini versão final.pdf: 760805 bytes, checksum: 819324cafda873d3eebae84919c69deb (MD5) / Approved for entry into archive by ROSANGELA APARECIDA LOBO null (rosangelalobo@btu.unesp.br) on 2018-04-06T19:40:00Z (GMT) No. of bitstreams: 1 ferreira_fp_me_bot.pdf: 760805 bytes, checksum: 819324cafda873d3eebae84919c69deb (MD5) / Made available in DSpace on 2018-04-06T19:40:00Z (GMT). No. of bitstreams: 1 ferreira_fp_me_bot.pdf: 760805 bytes, checksum: 819324cafda873d3eebae84919c69deb (MD5) Previous issue date: 2018-03-23 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Nas áreas de Ciências da Saúde e Biológicas, encontram-se vários estudos, considerando as mais variadas patologias. Contudo, os procedimentos de análise estatística utilizados nos dados não têm relevado a estrutura de variação envolvida no conjunto das variáveis biológicas, quando se procede o fracionamento para discutir cada variável isoladamente. No presente texto, será abordada a Remodelação Cardíaca em ratos com Estenose Aórtica induzida e submetidos a um determinado protocolo de Treinamento Físico, sob o aspecto de não fracionamento do conjunto de variáveis, a fim de considerar toda a estrutura de variação envolvida nas respostas biológicas. A Insuficiência Cardíaca (IC) é uma das principais causas de morte na atualidade. Em estudos experimentais, uma maneira de induzir a IC em um rato, para posteriormente estudar medidas que atenuem tal quadro clínico, é simulando uma Estenose Aórtica (EAo), por meio da implantação de um clipe milímetros acima de sua válvula aórtica. Estudos sugerem que treinamento físico suaviza os sintomas antecedentes à insuficiência cardíaca. A fim de comprovar tal hipótese, um grupo de pesquisadores da Cardiologia Experimental da Faculdade de Medicina de Botucatu - UNESP realizou alguns experimentos, em que ratos da variedade Wistar foram induzidos à Estenose Aórtica e, posteriormente, submetidos a um específico protocolo de treinamento físico. Para a avaliação da contribuição do treinamento na resposta cardíaca desses animais, outros ratos, aqui denominados Sham (sem implantação do clipe), também foram submetidos ao protocolo de treinamento. Portanto, quatro grupos foram formados: EAo (ratos induzidos à estenose aórtica); EAoTF (ratos induzidos à estenose aórtica e submetidos ao treinamento físico); Sham (sem treinamento físico); ShamTF (submetidos ao treinamento físico). Para o presente estudo, foram considerados apenas dois experimentos em que, no primeiro, foram mensuradas algumas variáveis a partir do ecocardiograma e do cardiomiócito isolado e, no segundo, do ecocardiograma e do músculo papilar. O objetivo foi utilizar técnicas multivariadas que considerem o estudo simultâneo das variáveis em cada experimento, visando concluir a respeito da inserção do treinamento físico como medida de atenuação do quadro clínico cardiológico. Os resultados das análises dos dados coletados, tanto do primeiro quanto do segundo experimento, mostraram que, de uma maneira geral, o treinamento físico ocasionou amenização das modificações cardiológicas presentes em animais induzidos à estenose aórtica, reaproximando em algumas características estes animais aos considerados saudáveis. / Heart failure (HF) is a leading cause of death nowadays. In experimental studies a way to induce the HF in a rats for subsequently studying measures that mitigate such clinical picture is simulating an aortic stenosis (EAo) through the implantation of a clip above the aortic valve. Studies suggest that physical training improves symptoms prior to heart failure. In order to prove this hypothesis, a group of researchers from the Experimental Cardiology of the Medical School of Unesp, Botucatu Campus, has made some experiments in which Wistar rats were induced to aortic stenosis and subsequently submitted to a specific protocol of physical training. For the assessment of the training contribution in cardiac response of these animals, other rats, here called Sham (without implantation of clip), also underwent the training protocol. Therefore, four groups were formed: EAo (rats induced to xv aortic stenosis); EAoTF (rats induced to aortic stenosis and submitted to physical training); Sham (without physical training); ShamTF (submitted to physical training). For this study were considered only two experiments in which at first were measured some variables from the echocardiogram and cardiomyocyte isolated and, in the second, the echocardiogram and papillary muscle. The goal of this research was to use multivariate techniques that consider the simultaneous study of the variables in each experiment aiming to conclude about the insertion of physical training as a mitigation of clinical cardiology. The results of the analyzes of both the first and the second experiments showed that, in general, physical training caused a slight alleviation of the cardiological changes present in animals induced to aortic stenosis, bringing closer in some characteristics these animals to those considered healthy

Bakgrund: Hjärtsvikt drabbar många personer såväl i Sverige som internationellt. Information är grundläggande för hantering av sjukdomen samt för att förebygga negativa följder. Som teoretisk utgångspunkt användes KASAM, känslan av sammanhang. Syfte: Att beskriva hjärtsviktspatienters erfarenheter av information. Metod: En litteraturöversikt med tolv kvalitativa artiklar har gjorts. Artiklarna har analyserats med Fribergs femstegsmodell. Resultat: I litteraturöversiktens resultat framkommer två teman, "Tillfredsställelse med information" samt "Former för information". Hjärtsviktspatienter hade skilda erfarenheter gällande information. Vissa patienter hade upplevt att informationen var tillfredsställande och tillräcklig medan andra upplevde informationen som bristande. Informationen som gavs upplevdes ofta vara i behov av anpassning utifrån patientens förutsättningar. Patienter hade erfarenheter av aspekter som såväl hindrade som underlättade information. I vissa fall använde patienter andra källor utöver vården för att hitta information. Slutsatser: För att omvårdnaden kring hjärtsviktspatienter ska bli tillgodosedd krävs att sjuksköterskan tar sig tid och ger anpassad information till patienterna. Sjuksköterskan bör se till att anpassa informationen utifrån patienternas förutsättningar, önskemål, resurser och behov. Litteröversikten visar att det finns rum för förbättring angående givning av information till hjärtsviktspatienter. / Background: Heart failure affect many people both in Sweden and internationally. Information is key to managing the illness and preventing negative consequences. KASAM (SOC), sense of coherence, was used as the theoretical starting point. Aim: To describe heart failure patients' experiences of information. Method: With Friberg's five step model as the analytic method, a literature review was conducted on twelve qualitative studies about heart failure patients' experiences of information. Result: The literature review's result shows two themes, "Satisfaction with Information" and "Forms of Information". Heart failure patients had different experiences concerning information. Some patients experienced the information as satisfactory and sufficient while others experience the information as lacking. The information that was given was often experienced as in need of adaptation to fit the patient's situation.  Patients had experiences of aspects that both hindered and facilitated information. In some cases, patients used sources other than the health care to find additional information. Conclusion: In nursing of heart failure patients the nurse has to take time to inform and to adapt information to the patients. The nurse should make sure to adapt the information after the patients' condition, wishes, resources and needs. The literature review shows that there's room for improvement concerning information given to heart failure patients.

Bakgrund: Hjärtsvikt är sex gånger vanligare hos patienter i 65-74 års åldern jämfört med patienter i 45-54 års åldern. Hjärtsvikt påverkar patienters hälsa och välbefinnande då hjärtsvikt påverkar den fysiska och psykiska förmågan. Symtomen vid hjärtsvikt leder till fler sjukhusvistelser och långa sjukskrivningar. Egenvården är en viktig del av behandlingen.  Trots fördelarna med egenvård genomför inte patienter egenvård. Patienter med hjärtsvikt är i behov av åtgärder som främjar deras egenvård. Syfte: Syftet var att beskriva faktorer som främjar patienters egenvård vid hjärtsvikt. Metod: Metoden i studien var en litteraturöversikt. 12 artiklar analyserades varav 10 av dessa var kvalitativa och 2 var av en mixad metod. Resultat: Det framkom att patienter önskade information om egenvård. Ett utbildningsprogram ökade genomförandet av egenvård. Patienter föredrog hemsjukvård före andra vårdformer då den ökade deras delaktighet. Kognitiv beteendeterapi kunde förändra patienters tankesätt och lindra depression. Stödet patienter fick från sjuksköterskor och familj hade en stor betydelse i genomförandet av egenvård. Motivationskällor och självförtroendet påverkade genomförandet av egenvård.  Slutsats: Patienter bör genomföra egenvård för att undvika symtomförsämring, sjukhusvistelser, sjukskrivningar och uppnå god hälsa och välbefinnande. Utbildning, kognitiv beteendeterapi, hemsjukvård, delaktighet, stöd, motivation och självförtroende främjar egenvård hos patienter med hjärtsvikt. / Background: Heart failure is six times more common among patients between the ages 65-74 compared to patients between the ages 45-54. Heart failure affects patients health and wellbeing. Heart failure symptoms lead to more hospitalizations and long sick leaves. Self-care is an important part of the treatment. Patients do not perform self-care despite the benefits of it. Patients with heart failure are in need of measures that promote their selfcare. Aim: the aim was to describe factors that promote patients self-care in heart failure. Method: The method of the study was a literature review. 12 articles were analyzed where 10 of them were qualitative and 2 of a mixed method. Result: Patients want information about self-care. An educational program enhances self-care. Patients prefer home healthcare because it increases their participation. Cognitive behavioral therapy can change patients thoughts and ease depression. The support patients receive from nurses and family members has a big effect on their self-care. Motivation and confidence affects self-care. Conclusion: Patients should perform self-care to avoid symptom deterioration, hospital visits, sick leave and achieve good health and well-being. Education, cognitive behavioral therapy, home healthcare, participation, support, motivation and confidence promote selfcare in patients with heart failure.

Objetivo: Desenvolver e testar um sistema de monitoramento à distância por short message service (SMS) para pacientes com insuficiência cardíaca (IC) agudamente descompensada. Método: A elaboração do protótipo foi desenvolvida em três etapas: a primeira, foi a definição de todas as funcionalidades previstas; a segunda, procurou a codificação dos módulos do programa; a terceira, consistiu na realização dos testes, para garantir seu funcionamento pleno. O programa desenvolvido enviava dois tipos de mensagens: com perguntas, que deveriam ser respondidas pelos pacientes, e com reforços educativos, que não necessitavam de respostas. Além disso, o sistema gerava alarmes em caso de ausência de resposta ou conforme um fluxograma para detectar congestão. Esta dinâmica permitia o contato imediato com o participante para confirmar os dados recebidos e dar orientações sobre as medidas necessárias para auxiliá-lo. Para o teste do protótipo, foram acompanhados 10 pacientes com internação por descompensação aguda da IC que estavam nas unidades clínicas ou na unidade de cuidados coronarianos do Hospital de Clinicas de Porto Alegre. Após a alta, as mensagens que exigiam respostas foram enviadas durante uma semana (duas pela manhã e duas à noite). Os SMS educativos foram enviados uma vez a cada dois dias. Resultados: Participaram do teste do protótipo, 10 pacientes. A média de idade foi de 67±13 anos. Os pacientes eram predominantemente do sexo masculino e moravam acompanhados por familiares. A fração de ejeção média foi de 35±7%. Dos 30 pacientes potencialmente elegíveis no período de teste, 14 foram incluídos. Destes, quatro não tiveram alta no momento do teste e um não completou o seguimento de sete dias por internação por síndrome coronariana aguda. Dos 264 SMS enviados, 247 foram respondidos. Dez dos SMS não respondidos coincidiram com a falta de luz gerada por fortes tormentas que ocorreram na cidade. Os demais SMS não foram respondidos porque os pacientes não os viram (quatro) ou porque eles esqueceram (três). O alarme foi acionado sete vezes: três pacientes acordaram com falta de ar durante duas noites consecutivas e quatro pacientes se sentiram mais cansados durante dois dias consecutivos. Nenhum paciente aumentou dois Kg em três dias. Todos os pacientes tomaram as medicações prescritas durante o seguimento. A enfermeira do estudo orientou os pacientes que geraram alarme no sistema. Conclusões: O sistema de monitoramento à distância foi desenvolvido com êxito e, durante o teste, foi possível detectar algumas limitações – que foram corrigidas. Entre os participantes que completaram o estudo, observamos uma alta taxa de resposta e evidência preliminar de melhorias na autogestão da IC. / Objective: To develop and test a short message service remote monitoring system for patients with acute decompensated heart failure (HF). Method: The elaboration of the prototype was developed in three stages: the first one was the definition of all the expected functionalities; the second sought coding of the program modules; the third consisted of the tests, which ensured its full operation. The program sent two types of messages: questions that should be answered by the patients, and educational reinforcements that did not require answers. In addition, the system generated alarms in case of no response or according to a flow chart to detect congestion in the patient previously created by the team. This system allows the immediate contact with the participant to confirm the received data and to give the necessary orientations to him. For the prototype test we included 10 patients hospitalized for acute decompensation of HF who were in the clinical units or coronary care unit of the Clinical Hospital of Porto Alegre. After discharge, messages that required responses were sent for one week (two in the morning and two in the evening). The educational SMS was sent once every two days. Results: Ten patients participated in the prototype test. The mean age was 67 ± 13. The patients were predominantly males and lived with relatives. The ejection fraction was 35 ± 7%. Of the 30 potentially eligible patients in the trial period, 14 were included. Of these, four were not discharged at the time of the test and one did not complete the seven-day follow-up for hospitalization for acute coronary syndrome. Of the 264 SMS sent, 247 were answered. Ten of the unanswered SMS coincided with the lack of light generated by the strong storms in the city. The remaining SMS were not answered because the patients did not see them (four) or they forgot these (three). The alarm was triggered seven times: three patients woke up with shortness of breath for two consecutive nights and four patients felt more fatigued for two consecutive days. No patient increased two Kg in three days. All patients took the prescribed medications during follow-up. The study nurse guided the patients who generated alarm in the system. Conclusions: The remote monitoring system was successfully developed and during the test it was possible to visualize some limitations that were corrected. Among the participants who reform the study, we observed a high response rate and preliminary evidence of improvements in self-management of HF.

Heart failure induced by cardiac hypertrophy is a cause of high mortality in the world and has been the fastest growing cardiovascular disease over the past decade. Cardiac hypertrophy is characterised as a reactive increase in cardiac mass growth with a complex of ventricular remodelling. It occurs initially as a compensatory response to an increased workload but eventually leads to cardiac dysfunction. An in-depth understanding of cardiac hypertrophy and the capacity to regulate it has profound clinical implications. The MAPK pathways provide an important connection between external stimuli and intracellular signals for cardiac hypertrophic response. At least four MAPK subfamilies have been identified: extracellular-regulated protein kinases 1 and 2 (ERK1/2), ERK5, c-Jun NH2-terminal protein kinases (JNKs) and p38 MAPKs. Mitogen-activated protein kinase kinase 4 (MKK4), a vital activator of JNK and p38 is implicated as an important mediator of hypertrophy. ERK5, an atypical MAPK, is also involved in both hypertrophic growth and cardiomyocyte survival. However, conflicting data have been yielded from previously-published studies, since the results are based entirely on experiments conducted in cultured cardiomyocytes or transgenic and conventional knockout mouse models. To elucidate their biological roles and underlying signalling mechanisms in hypertrophy, mice with a cardiomyocyte-specific deletion of MKK4 or ERK5 (MKK4cko and ERK5cko mice) were generated in the present study. In response to pathological hypertrophic stresses including pressure overload or isoprenaline stimulation, MKK4cko mice developed exacerbated pathological hypertrophy with increased cardiomyocyte apoptosis, impaired cardiac function and remarkably upregulated NFAT (nuclear factor of T-cell) transcriptional activity. However, MKK4cko mice exhibited a similar extent of swimming exercise-induced physiological hypertrophy compared with the controls. In response to pathological hypertrophic stimuli, ERK5cko mice were resistant to hypertrophic growth, foetal gene induction and ventricular fibrosis, which is associated with repressed activation of MEF2 (myocyte enhancer factor 2). ERK5 deficiency also caused a profound increase in cardiomyocyte apoptosis which accounted for the impaired cardiac function. In conclusion, the present study provides biological evidence that clarifies in vivo functions of MKK4 and ERK5 in hypertrophy. MKK4 acts a protective role against pathological hypertrophy through inhibiting NFAT signalling, but it is not necessary for the regulation of physiological hypertrophy. ERK5 is essential for pathological hypertrophic remodelling and cardiomyocyte survival and its function in hypertrophic remodelling is mediated through regulation of MEF2 activity. Taken together, these data presented in my thesis advances knowledge about biological functions of MAPK pathways in the heart.

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Diabetes is a chronic and debilitating disease that affects nearly half a billion people worldwide with the vast majority of diabetics suffering from Type 2 diabetes mellitus (T2DM), a disease characterized by insulin insensitivity that often requires pharmacotherapy to effectively maintain target blood sugar levels. The thiazolidinedione (TZD) class of drugs consists of oral hypoglycaemic agents used alone or in combination with other antidiabetic drugs to treat T2DM. The drugs within this class, which include rosiglitazone and pioglitazone, were originally heralded as providing novel first and second-line treatment of T2DM with glycaemic control and physiological effects comparable to, and in some cases, better than, first-line treatments such as metformin. However, over time they have also been associated with adverse cardiovascular, osteological, and carcinogenic effects in some, but not all clinical trials, observational studies, and meta-analyses. Given the conflicting evidence to date on the safety of TZD drugs, their role in the treatment of T2DM continues to be debated and epidemiological gaps remain. The objectives of this doctoral research are fourfold: 1) to conduct an in-depth review of the epidemiology of TZD pharmacotherapy including pharmacokinetics and modes of action, the results of previous studies investigating health risks and benefits associated with TZD treatment, and new and future uses for this class of drugs; 2) to determine whether diabetic patients treated with TZDs are at increased risk of adverse cardiovascular outcomes; 3) to assess whether TZD pharmacotherapy is associated with an increased risk of bone fractures and whether risks differ depending on fracture site and patient sex; and, 4) to investigate associations between TZD use and risk of bladder cancer. Specific research questions were investigated using nested case-control analyses designed to capture incident users of antidiabetic drugs and electronic health data from Cerner Health Facts®, an electronic medical record database that stores time-stamped patient records from more than 480 contributing hospitals throughout the United States. Findings from this work are reported in a series of manuscripts, including a published review paper. Key findings include: 1) TZD use was associated with an increased risk of incident myocardial infarction and congestive heart failure compared to never use of TZD drugs with a trend towards a potential early treatment effect within the first year of exposure to pioglitazone; 2) TZD use was associated with an increased risk of closed bone fractures among Type 2 diabetics with use of pioglitazone or rosiglitazone associated with an increased risk across multiple fracture sites in women, but only rosiglitazone use in men and only at peripheral fracture sites; 3) use of either pioglitazone or rosiglitazone were associated with an increased risk of incident bladder cancer compared to never users, however, a low number of bladder cancer cases resulted in underpowered analyses; and, 4) insulin use in a hospital setting may replace a patient's normal course of antidiabetic therapy which, when combined with other potential sources of bias in traditional nested case-control studies using hospital-based data, may lead to overestimation or underestimation of adverse health risks associated with non-insulin antidiabetic therapies. Although these findings warrant replication, the results of the research contained within this dissertation suggest that caution should be exercised when prescribing diabetic patients TZD drugs if they have cardiovascular, osteological, or carcinogenic risk factors. Additional pharmacovigilance studies should also continue to strive to better understand the health risks related to TZD therapy, especially as new therapeutic roles for TZDs in the prevention and treatment of some cancers, inflammatory diseases, and other conditions in non-diabetic populations are being explored.

O objetivo desse estudo foi determinar se os índices de função, volume (VAE) e área (AAE) do átrio esquerdo (AE) podem ser utilizados para avaliar a gravidade da degeneração valvar crônica de mitral (DVCM) em cães, bem como diagnosticar a insuficiência cardíaca congestiva (ICC) nestes pacientes. A hipótese é que o aumento dos volumes e decréscimo da função atrial esquerda possa estar associado com a gravidade da DVCM e também com a ICC. Oitenta cães foram incluídos em um estudo clínico transversal observacional e prospectivo, sendo agrupados de acordo com a gravidade DVCM. Os cães foram igualmente distribuídos nos grupos A, B1, B2 e C + D, de acordo com o estadiamento para DVCM proposto pelo American College of Veterinary Internal Medicine. A mudança fracional da área (FAC) e a fração de ejeção atrial esquerda (FEAE) foram calculados com as seguintes equações: FAC total = 100 x (AAEmáxima AAEmínima) / AAEmáxima, FAC passiva = 100 x (AAEmáxima AAEpa) / AAEmáxima e FAC ativa = 100 x (AAEpa AAEminima) / AAEpa, cujas as mensurações foram realizadas no corte apical quatro câmaras; e FEAE Total = 100 x (VAEmáxima VAEmínima) / VAEmáxima, FEAE passiva = 100 x (VAEmáxima VAEpa) / VAEmáxima e FEAE ativa = 100 x (VAEpa VAEminima) / VAEpa, calculadas por meio do método biplanar área-comprimento, no corte apical quatro e duas câmaras. A FAC total, FAC ativa, FEAE total e FEAE ativa foram significativamente menores nos pacientes do grupo C+D do que as observadas nos demais grupos. Também foi observado que com o agravamento da DVCM ocorreu o aumento do VAEmáximo/kg, VAEpa/kg, VAEmínimo/kg, AAEmáximo/m2, AAEpa/m2, AAEmínimo/m2. Os volumes do AE, bem como suas áreas, apresentaram grande acurácia e aumentaram a capacidade para diagnosticar a ICC nos cães do DVCM. Conclui-se que a função atrial esquerda total e ativa é reduzida nos cães com ICC secundária a DVCM quando comparados aos cães saudáveis e naqueles com DVCM sem ICC. Além disso, os volumes e as áreas atriais podem ser utilizados para diagnosticar a ICC nesses pacientes / This study aimed to determine whether left atrial (LA) function indices, volume (LAV) and area (LAA) can be used to assess severity of mitral valve chronic degeneration (MVCD) in dogs, as well as to diagnose congestive heart failure (CHF) in these patients. The hypothesis stated that the increase in left atrial volumes and decrease in function are associated with the severity of MVCD and also with CHF. Eigthy dogs were included in a cross sectional prospective observational clinical study, grouped according to the severity of MVCD based on clinical signs and echocardiographic evaluation. Dogs were equitatively distribuited among groups A, B1, B2 and C + D, according to MVCD staging proposed by the American College of Veterinary Internal Medicine. The fractional area change (FAC) and left atrial ejection fraction (LAEF) were calculated based on the following equations: total FAC = 100 x (LAAmaximum LAAminimum) / LAAmaximum, passive FAC = 100 x (LAAmaximum LAApa) / LAAmaximum and active FAC ativa = 100 x (LAApa LAAminimum) / LAApa, which measurements were performed in four chamber apical view; and total LAEF = 100 x (LAVmaximum LAVminimum) / LAVmaximum, passive LAEF = 100 x (LAVmaximum LAVpa) / LAVmáximum and active LAEF = 100 x (LAVpa LAVminimum) / VLAVpa , calculated by biplanar arealength method in four and two-chambers apical view. The total and active FAC, total LAEF and active LAEF were significantly smaller in pacients from group C+D than the observed in the other groups. With increasing severity of MVCD there was increase in LAVmaximum/kg, LAVpa/kg, LAVminimum/kg, LAAmaximum/m2, LAApa/m2, LAAminimum/m2. LA volumes, as well as LA areas had a good performance as diagnostic methods, with high accuracy and increased capacity for heart failure detection in dogs with MVCD. In conclusion, left atrial total and active function are reduced in dogs with HF secondary to MVCD when compared with healthy dogs and dogs with MVCD without HF. Moreover, atrial volumes and areas can be used to diagnose HF in these patients

Introdução: Níveis de fator de necrose tumoral–alfa (TNF-α), N-peptídeo do pró-colágeno III (PIIINP) e metaloproteinase de matriz –1 (MMP-1), marcadores biológicos de remodelamento ventricular, estão elevados em pacientes com insuficiência cardíaca (IC), talvez refletindo elevadas pressões de enchimento. A correlação destes marcadores com variáveis clínicas e hemodinâmicas permanece pouco compreendida, particularmente no contexto ambulatorial da IC. Objetivo: Avaliar níveis séricos de marcadores biológicos de remodelamento ventricular em pacientes com IC, comparando tratamento guiado por ecocardiografia (ECO), buscando redução de pressões de enchimento, versus tratamento convencional (CLÍNICO), baseado em sinais e sintomas. Métodos: Ensaio clínico randomizado. Pacientes estáveis com IC e fração de ejeção menor do que 40% foram alocados entre os grupos de tratamento e submetidos a ecocardiograma e coletas de sangue no início do estudo e em 180 dias. TNF-α e MMP- 1 foram medidos por ELISA, e PIIINP, por radioimunoensaio. Resultados: Incluiu-se 80 pacientes, com 59 ± 15 anos e fração de ejeção de 26 ± 7%; 25% isquêmicos e 52% masculinos. Houve redução dos marcadores biológicos intragrupos, não havendo diferença entre os tratamentos. No grupo CLÍNICO, os níveis de TNF-α, MMP-1 e PIIINP apresentaram diferenças estatisticamente significativas entre os momentos basal e final (respectivamente, 3,11 ± 2,90 versus 1,24 ± 0,60 pg/mL p < 0,0003; 2,66 ± 1,00 versus 1,16 ± 0,40 ng/mL p < 0,0001; 6,12 ± 2,60 versus 3,89 ± 1,60 μg/L p < 0,0001). De maneira semelhante, tal diferença também foi observada no grupo ECO para os três marcadores (respectivamente, 3,90 ± 4,90 versus 1,40 ± 1,30 pg/mL p < 0,0001; 2,50 ± 0,90 versus 1,09 ± 0,40 ng/mL p < 0,0001; 6,09 ± 2,60 versus 3,50 ± 1,30 μg/L p<0,0001). Ao final da intervenção, no entanto, não foi observada diferença significativa dos valores de TNF-α , MMP-1 e PIIINP entre os dois grupos de tratamento (p = 0,7; p = 0,8; e p = 0,2; respectivamente). A combinação dos valores basais das variáveis biológicas gerou um escore que se associou significativamente com o comportamento final das pressões atrial direita e sistólica da artéria pulmonar. Pacientes com marcadores biológicos basais no quartil 75% mantiveram níveis superiores de pressões atrial direita (13 mmHg; p = 0,034) e sistólica de artéria pulmonar (60 mmHg; p = 0,007) ao final do seguimento. Conclusão: Independente do tratamento alocado, houve redução dos níveis de marcadores biológicos ao final do seguimento; no entanto, níveis basais mais elevados destes marcadores foram preditores de menor redução das pressões em átrio direito e sistólica da artéria pulmonar. Os dados sugerem que indicativos de intenso processo de remodelamento ventricular se associam à progressão da IC e a pressões de enchimento elevadas. / Introduction: Levels of tumor necrosis factor-alpha (TNF-α), N-terminal propeptide of type III collagen (PIIINP) and type 1 matrix metalloproteinase (MMP-1), biological markers of ventricular remodeling, are elevated in heart failure (HF) patients, perhaps reflecting elevated filling pressures. The correlation of these markers with clinical and hemodynamic variables remains poorly understood, particularly in the outpatient setting. Objective: To evaluate serum levels of ventricular remodeling biological markers in patients with HF, comparing a conventional clinically-oriented treatment (Conventional Therapy), based on clinical signs and symptoms, to an echocardiography-guided treatment (Echo-guided Therapy), aiming at a reduction in filling pressure levels. Methods: Randomized trial. Stable patients with HF and ejection fraction lower than 40% were allocated to the treatment groups and submitted to echocardiography and blood sampling at the beginning of the study and after 180 days. TNF-α and MMP-1 were measured by ELISA, and PIIINP, by radioimmunoassay. Results: Eighty patients at 59 ± 15 years and a mean ejection fraction of 26 ± 7% were included; 25% were ischemic and 52%, males. There was a reduction in intragroup biological markers, without difference between treatments. TNF-α, MMP-1 and PIIINP levels were statistically different between baseline and final in patients allocated to Conventional Therapy (respectively, 3.11 ± 2.90 versus 1.24 ± 0.60 pg/mL p < 0.0003; 2.66 ± 1.00 versus 1.16 ± 0.40 ng/mL p < 0.0001; 6.12 ± 2.60 versus 3.89 ± 1.60 μg/L, p < 0.0001). Similarly, such a difference was also observed in the Echo-guided Therapy for the 3 markers (respectively, 3.90 ± 4.90 versus 1.40 ± 1.30 pg/mL p < 0.0001; 2.50 ± 0.90 versus 1.09 ± 0.40 ng/mL p < 0.0001; 6.09 ± 2.60 versus 3.50 ± 1.30 mg/L p<0.0001). By the completion of the intervention, however, no significant difference was observed in the values of TNF-α, MMP- 1 and PIIINP between the 2 treatment groups (p = 0.7; p = 0.8; and p = 0.2; respectively). A composite score incorporating baseline biological marker levels was statistically associated to final right-sided pressure levels (right atrial pressure and pulmonary artery systolic pressure). Patients with baseline biological marker levels over percentile 75 maintained higher right atrial (13 mmHg; p = 0.034) and pulmonary artery systolic pressures (60 mmHg; p = 0.007) at the end of protocol. Conclusion: Regardless of allocated treatment group, biological marker levels were lower at the end of the follow-up; however, higher baseline levels of these markers were predictive of lower reductions in right atrial pressure and pulmonary artery systolic pressure. The data obtained suggest that indicators of an intense remodeling process are associated with elevated filling pressures and progression of HF.