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El texto completo de este trabajo no está disponible en el Repositorio Académico UPC por restricciones de la casa editorial donde ha sido publicado. / Objective The objective of this study was to investigate the effect of preoperative diastolic dysfunction on postoperative mortality and morbidity after cardiovascular surgery. Methods We systematically searched for articles that assessed the prognostic role of diastolic dysfunction on cardiovascular surgery in PubMed, Cochrane Library, Web of Science, Embase and Scopus until February 2016. Twelve studies (n=8224) met our inclusion criteria. Due to scarcity of outcome events, fixed-effects meta-analysis was performed using the Mantel-Haenszel method. Results Preoperative diagnosis of diastolic dysfunction was associated with higher postoperative mortality (OR 2.41, 95% CI 1.54-3.71; p<0.0001), major adverse cardiac events (MACE) (OR 2.07, 95% CI 1.55-2.78; p <=0.0001) and prolonged mechanical ventilation (OR 2.08, 95% CI 1.04-4.16; p=0.04) in comparison to patients without diastolic dysfunction among patients who underwent cardiovascular surgery. The odds of postoperative myocardial infarction (OR: 1.29, 95% CI 0.82, 2.05; p=0.28) and atrial fibrillation (OR: 2.67; 95% CI 0.49-14.43; p=0.25) did not significantly differ between the two groups. Severity of preoperative diastolic dysfunction was associated with increased postoperative mortality (OR 21.22, 95% CI 3.74 -120.33; p=0.0006) for Grade 3 diastolic dysfunction compared with patients with normal diastolic function. Inclusion of left ventricular ejection fraction (LVEF) <40% accompanying diastolic dysfunction, did not further impact postoperative mortality (p=0.27; I2 =18%) when compared with patients with normal LVEF and diastolic dysfunction. Conclusions Presence of preoperative diastolic dysfunction was associated with higher postoperative mortality and MACE, regardless of LVEF. Mortality was significantly higher in grade III diastolic dysfunction. Keywords Diastolic dysfunction; cardiovascular surgical procedures; mortality; meta-analysis / Revisión por pares

Orientador: Regina Kiomi Takahira / Resumo: A miocardiopatia hipertrófica é a doença cardíaca mais observada em gatos da raça Maine Coon e está diretamente relacionada à presença de uma mutação (A31P) que ocorre no gene da proteína C miosina ligante (MYBPC3). A doença pode provocar em determinados pacientes quadros secundários graves como o tromboembolismo arterial (TEA). O objetivo do presente trabalho foi avaliar gatos da raça Maine Coon não portadores da mutação A31P no gene MYBPC3 (G1) e portadores da mutação A31P no gene MYBPC3 (G2), por meio do perfil tromboelastométrico. Foram selecionados no estudo 15 gatos pertencentes ao grupo G1 e 15 gatos G2, previamente avaliados para A31P-MYBPC3, tendo como critério de inclusão a presença ou não da mutação e higidez clínica e laboratorial para hemograma e provas de bioquímicas séricas. A coleta das amostras ocorreu em momento único após avaliação ecocardiográfica. A análise estatística foi realizada por meio de análise descritiva dos dados seguida da comparação dos grupos ao nível de 5 % de significância. No presente estudo o perfil pela tromboelastometria (TEM) não identificou diferenças quando comparados os grupos G1 e G2, portanto os animais não demonstraram variações de coagulabilidade. A concentração sérica de albumina foi significativamente menor no G2, mas se manteve dentro dos intervalos de referência para a espécie. No ecocardiograma foi observada alteração no volume diastólico final no G2, indicando a presença de possível disfunção diastólica. O G2 também aprese... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Hypertrophic cardiomyopathy is the most observed heart disease in Maine Coon cats and is directly related to the presence of a mutation (A31P) occurring in the myosin binding protein C (MYBPC3) gene. The disease can cause serious side effects such as arterial thromboembolism (ATE) in certain patients. The objective of the present study was to evaluate the thromboelastometric profile in cats Maine Coon breed without mutation A31P on MYBPC3 gene (G1) and mutation carrier (G2). Thirty cats previously evaluated for A31P-MYBPC3 were divided into G1 and G2 groups (n=15). The inclusion criteria were the presence or absence of mutation and clinical data, blood counts and serum biochemistry within reference intervals. The samples were taken at a single moment after an echocardiographic evaluation. Statistical analysis was performed through descriptive data analysis followed by comparison of groups at the 5% level of significance. In the present study, the profile by thromboelastometry (TEM) did not identify differences when comparing groups G1 and G2, and the animals showed no coagulability variations. Serum albumin concentration was significantly lower in the mutation carrier group (G2), but it remained within the reference intervals for the species. On the echocardiogram, a change in final diastolic volume was observed in the carrier group, indicating that the carrier animals should be evaluated to previous identification of possible diastolic dysfunction. The carrier group also pre... (Complete abstract click electronic access below) / Doutor

Resumo: A insuficiência cardíaca (IC) é uma síndrome grave associada a alta mortalidade em 5 anos, após o início dos sintomas. Portanto, é de interesse o estudo de tratamentos farmacológicos e não-farmacológicos que visem impedir a progressão da lesão miocárdica, reduzir os sintomas e melhorar a qualidade de vida. Uma das formas de tratamento não farmacológico é o uso de Pressão Positiva Contínua em Vias Aéreas (CPAP). Estudos mostraram que a CPAP está associada com melhora da função sistólica ventricular esquerda. Entretanto, há poucos dados na literatura referentes aos seus efeitos na função diastólica. Objetivos: o objetivo primário desse estudo foi avaliar os efeitos de sessão única de CPAP na função diastólica ventricular e na capacidade funcional de pacientes com IC compensada. Adicionalmente, foram analisadas, nesses pacientes, as associações entre capacidade funcional e função ventricular; capacidade funcional e qualidade de vida; e função ventricular e qualidade de vida. Estudo prospectivo, randomizado e duplo-cego, utilizando programa informatizado de números aleatórios, na proporção 1:1. Vinte e um pacientes foram alocados no grupo sham (ou CPAP simulado) e 23 no grupo CPAP, que recebeu a intervenção. Os pacientes, inicialmente, permaneciam 10 minutos em repouso e passavam por avaliação clínica. Em seguida, eram submetidos a ecocardiograma basal. Então, realizavam Teste de caminhada de 6 minutos (TC6) para aprendizagem, sendo que os dados obtidos nesse teste foram descartados. Enquanto descansavam por, no mínimo, 15 minutos, os pacientes respondiam ao Questionário de Qualidade de Vida de Minnesota (QQVM). Após, realizavam um segundo TC6, no qual os dados foram utilizados para análise. Ao seu término, os pacientes do Grupo CPAP recebiam a intervenção por 30 minutos a uma pressão de 10 cmH20. O pacientes do Grupo Sham permaneciam... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Heart failure (HF) is a syndrome associated with high mortality within 5 years after the onset of symptoms. Therefore) the study on pharmacological and non-pharmacological therapies for preventing myocardial damage progression) reducing symptoms and improving quality of life is desirable. One of the forms of non-drug treatment is the use of Continuous Positive Airway Pressure (CPAP). Studies have shown that CPAP is associated with left ventricular systolic function improvement. However) few data are available referring to its effects on diastolic function. The primary aim of this study was to evaluate the effects of a single CPAP session on ventricular diastolic function and on the functional capacity of patients with compensated HF. Additionally) the associations between functional capacity and ventricular function) functional capacity and quality of life and ventricular function and quality of Iife were analyzed in these patients. This was a prospective) randomized) double-blind study using a random-figure computerized program in the proportion of 1:1. Twenty-one patients were included in the Sham group (or simulated CPAP) and 23 in the CPAP group) which received the intervention. Initially) the patients rested for 10 minutes and then underwent c1inical evaluation. Next) they were submitted to a basal echocardiogram. Then) the six-minute walk test (6MWT) was performed for learning) and the data obtained in that test were discarded. While they rested for at least 15 minutes) the patients answered the Minnesota Living with Heart Failure Questionnaire (MLHFQ). They then performed the second 6MWT) in which the data were used for analysis. Upon completion) the patients in the CPAP group received the intervention for 30 minutes at apressure of 10 cmH20. The patients in the Sham group kept the CPAP mask on for that period of time) but without producing positive pressure. Next)... (Complete abstract click electronic access below) / Orientador: Beatriz Bojikian Matsubara / Coorientador: Silméia Garcia Zanati / Banca: Victor Zunica Dourado / Banca: Audrey Borghi e Silva / Mestre

名古屋大学博士学位論文 学位の種類 : 医学博士(論文) 学位授与年月日:平成4年7月20日 宮口和彦氏の博士論文として提出された

In the first half of this work, titin's role in cardiac function was studied using intact cardiac myocytes. The development of a carbon fiber based cell-attachment system allowed diastolic and systolic function of the isolated intact myocyte to be investigated. Addition of actomyosin inhibitor to the intact myocyte revealed that the majority of the cell's diastolic stiffness is due to titin but that actomyosin interaction exists as well and contributes ~ 30% of total diastolic stiffness. The details of this study are provided in chapter 1. Heart failure with preserved ejection fraction (HFpEF) accounts for up to 50% of total heart failure cases and is characterized by increased diastolic stiffness. An effective treatment for HFpEF does not exist. Reducing titin stiffness as a therapeutic strategy for lowering left ventricular (LV) chamber stiffness in HFpEF is currently under consideration. To understand the functional consequence of reduced titin stiffness on global cardiac function a Rbm20 Δᴿᴿᴹ mouse model was created. The Rbm20 Δᴿᴿᴹ model has deficiency in titin splicing that results in expression of very large and compliant titin isoforms in the sarcomeres. Study of Rbm20 Δᴿᴿᴹ cells revealed that cellular diastolic stiffness was inversely related to the size of titin and was reduced in a graded manner in Rbm20 Δᴿᴿᴹ heterozygous (+/-) and homozygous (-/-) cells. Importantly, reduced titin-based stiffness manifested in vivo as reduced LV chamber stiffness, which could be observed by echocardiography and pressure volume (PV) analysis. The systolic function of Rbm20 Δᴿᴿᴹ was studied by measuring the Frank-Starling mechanism (FSM), first at the intact myocyte level. The FSM was reduced in Rbm20 Δᴿᴿᴹ +/- and -/- with the largest reduction in -/- cells. PV analysis demonstrated a reduced FSM at the LV chamber level, consistent with the result at the cellular level. Surprisingly, exercise testing showed an enhanced exercise performance in cardiac specific Rbm20 Δᴿᴿᴹ +/- mice (relative to wild-type mice). Thus, this work indicates that increasing titin compliance improves diastolic function but negatively impacts systolic function. Importantly, findings suggest that the beneficial effect of improving diastolic function is a dominant effect. This work is described in Chapter 2.

Recent studies support the association between metabolic syndrome (MetS), a cluster of cardiovascular risk factors, and diastolic dysfunction. Disproportionate collagen accumulation, particularly cross-linking of collagen, plays a key role in translating interstitial fibrosis into mechanical chamber stiffness and diastolic dysfunction. Characteristic changes in the expression and activity of myocardial lysyl oxidase (LOX), a matrix modifying enzyme that catalyzes cross-linked collagen, are unclear in MetS. We established a diet-induced MetS model to study diastolic dysfunction by treating male C57BL/6 mice a high-fat high-simple carbohydrate (HFHSC) diet for 6 months. Despite blunted gene expression of LOX isoforms, MetS mice demonstrated significant increase in the ratio of protein expression of mature to proenzyme LOX, enhanced LOX activity, and increased cardiac cross-linked collagen compared with controls. This fibrotic response coincided with marked increase in left ventricular end-diastolic pressure and stiffness and impaired diastolic filling pattern. Our data demonstrate that diet-induced MetS alters the remodeling enzyme LOX, thereby increasing the amount of crosslinking and inducing diastolic dysfunction.Furthermore we examined the role of T-lymphocytes in myocardial LOX regulation in diet-induced fibrotic hearts. Female SCID mice which are devoid of functional T-lymphocytes and C57BL/6 mice were treated with HFHSC diet for 12 months. Similar to male C67BL/6, female HFHSC-fed C57BL/6 mice demonstrated significant increase in maturation and catalytic activity of myocardial LOX, cross-linking, ventricular stiffness and diastolic dysfunction. Whereas induction of LOX protein was minimal in SCID mice compared with wild-type counterparts. Correspondingly fibrillar cross-linked collagen formation and diastolic dysfunction were less prominent in SCID mice. Our results suggest a potential role of T-lymphocytes in induction of myocardial stiffness and diastolic dysfunction through modulation of LOX-dependent collagen maturation.Moreover we studied the role of leptin, an adipokine over-produced in MetS with fibrotic effects in non-cardiac tissues, as a key mediator of profibrogenic responses in the heart by administrating leptin to C57BL/6 and leptin-deficient ob/ob mice. With exogenous leptin administration ob/ob mice displayed passive diastolic filling dysfunction that coincided with increase in myocardial collagen compared with ob/ob controls. Our findings suggest profibrotic effects of leptin in the heart, primarily through predominance of collagen synthesis over degradation.

No description available.

Made available in DSpace on 2014-06-11T19:25:36Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-02-17Bitstream added on 2014-06-13T20:14:17Z : No. of bitstreams: 1 bussoni_mf_me_botfm.pdf: 519756 bytes, checksum: c724f1d40d7988265c8b8b601c44ca60 (MD5) / A insuficiência cardíaca (IC) é uma síndrome grave associada a alta mortalidade em 5 anos, após o início dos sintomas. Portanto, é de interesse o estudo de tratamentos farmacológicos e não-farmacológicos que visem impedir a progressão da lesão miocárdica, reduzir os sintomas e melhorar a qualidade de vida. Uma das formas de tratamento não farmacológico é o uso de Pressão Positiva Contínua em Vias Aéreas (CPAP). Estudos mostraram que a CPAP está associada com melhora da função sistólica ventricular esquerda. Entretanto, há poucos dados na literatura referentes aos seus efeitos na função diastólica. Objetivos: o objetivo primário desse estudo foi avaliar os efeitos de sessão única de CPAP na função diastólica ventricular e na capacidade funcional de pacientes com IC compensada. Adicionalmente, foram analisadas, nesses pacientes, as associações entre capacidade funcional e função ventricular; capacidade funcional e qualidade de vida; e função ventricular e qualidade de vida. Estudo prospectivo, randomizado e duplo-cego, utilizando programa informatizado de números aleatórios, na proporção 1:1. Vinte e um pacientes foram alocados no grupo sham (ou CPAP simulado) e 23 no grupo CPAP, que recebeu a intervenção. Os pacientes, inicialmente, permaneciam 10 minutos em repouso e passavam por avaliação clínica. Em seguida, eram submetidos a ecocardiograma basal. Então, realizavam Teste de caminhada de 6 minutos (TC6) para aprendizagem, sendo que os dados obtidos nesse teste foram descartados. Enquanto descansavam por, no mínimo, 15 minutos, os pacientes respondiam ao Questionário de Qualidade de Vida de Minnesota (QQVM). Após, realizavam um segundo TC6, no qual os dados foram utilizados para análise. Ao seu término, os pacientes do Grupo CPAP recebiam a intervenção por 30 minutos a uma pressão de 10 cmH20. O pacientes do Grupo Sham permaneciam... / Heart failure (HF) is a syndrome associated with high mortality within 5 years after the onset of symptoms. Therefore) the study on pharmacological and non-pharmacological therapies for preventing myocardial damage progression) reducing symptoms and improving quality of life is desirable. One of the forms of non-drug treatment is the use of Continuous Positive Airway Pressure (CPAP). Studies have shown that CPAP is associated with left ventricular systolic function improvement. However) few data are available referring to its effects on diastolic function. The primary aim of this study was to evaluate the effects of a single CPAP session on ventricular diastolic function and on the functional capacity of patients with compensated HF. Additionally) the associations between functional capacity and ventricular function) functional capacity and quality of life and ventricular function and quality of Iife were analyzed in these patients. This was a prospective) randomized) double-blind study using a random-figure computerized program in the proportion of 1:1. Twenty-one patients were included in the Sham group (or simulated CPAP) and 23 in the CPAP group) which received the intervention. Initially) the patients rested for 10 minutes and then underwent c1inical evaluation. Next) they were submitted to a basal echocardiogram. Then) the six-minute walk test (6MWT) was performed for learning) and the data obtained in that test were discarded. While they rested for at least 15 minutes) the patients answered the Minnesota Living with Heart Failure Questionnaire (MLHFQ). They then performed the second 6MWT) in which the data were used for analysis. Upon completion) the patients in the CPAP group received the intervention for 30 minutes at apressure of 10 cmH20. The patients in the Sham group kept the CPAP mask on for that period of time) but without producing positive pressure. Next)... (Complete abstract click electronic access below)