Le ventricule droit (VD) fut longtemps oublié par les cardiologues mais l'expérience a montré qu'il conditionne le pronostic des patients dans de nombreuses situations cliniques et que l'évaluation de sa fonction est un élément diagnostique majeur lorsqu'une pathologie du VD est suspectée. Après une revue des différentes méthodes d'évaluation de la fonction ventriculaire droite, cette thèse explore tout d'abord les limites des deux méthodes d'évaluation du VD les plus répandues (IRM et échographie) : Premièrement, les indices de contraction longitudinale en échographie ne permettent pas de dépister correctement les altérations de la fraction d'éjection dans la situation d'une surcharge volumétrique notamment. Deuxièmement, l'IRM en coupes petit-axe présente des difficultés importantes de délinéation de l'endocarde. Les principaux écarts de contours entre deux observateurs concernent l'infundibulum pour 40% et la valve tricuspide pour 40% également. Dans une troisième partie, nous proposons un indice géométrique simple à calculer lors d'un examen IRM et permettant de pré-sélectionner les patients nécessitant une étude précise du VD. Cet indice validé sur 340 patients réduit le temps opérateur de 35% sans entrainer d'erreur diagnostique. La dernière partie de cette thèse s'intéresse à la mesure de la vitesse tissulaire du myocarde et aux indices fonctionnels qui en dérivent. Cette mesure nécessite une haute résolution temporelle qui peut être atteinte en IRM en respiration libre au prix d'une augmentation de la durée d'acquisition / The right ventricle (RV) has been neglected for a long time by cardiologists. Only recently, it has been pointed out as yielding pronostic or diagnostic value in numerous clinical situations. This thesis, after a review of the different methods used to assess the right ventricular function, stresses the limitations of the two most used methods to assess RV function: 1) Long-axis contraction indices fail to predict ejection fraction in a volumetric overload situation. 2) Short-axis MRI relies upon a rather difficult manual contouring of the endocardium. The main variation in this contouring occurs in the infundibulum (40%) and in the basal part around the tricuspid valve (40%). Then, we propose a novel geometric indice, easy to compute during a MRI examination and aimed to select the patients needing an accurate RV study. This index was validated within 340 patients and reduced the operator time of 35% without inducing any diagnostic error. The last part of this thesis concerns tissue phase-mapping. High temporal resolution is the key point for the accuracy of myocardial velocities and can be achieved by a simple averaging during free-breathing at the expense of longer acquisitions

INTRODUÇÃO: Historicamente, os procedimentos de revascularização do miocárdio (cirúrgicos ou percutâneos) foram admitidos como opções terapêuticas efetivas para a proteção, em curto e médio prazo, do miocárdio isquêmico em pacientes portadores de doença arterial coronária. Todavia, não está estabelecido se tais procedimentos são essenciais para a preservação da função ventricular, nem se a ausência dos mesmos contribui para sua piora. OBJETIVOS: Avaliar a evolução da fração de ejeção (FEVE) em pacientes portadores de doença multiarterial coronariana crônica estável, e com função ventricular esquerda preservada, dez anos após terem sido submetidos a três diferentes estratégias terapêuticas: revascularização cirúrgica do miocárdio (RM), angioplastia coronária percutânea (ATC) ou tratamento medicamentoso (TM) isoladamente (subestudo do MASS II). MÉTODOS: Realizou-se o ecocardiograma transtorácico com doppler para avaliação da FEVE em pacientes portadores de DAC multiaterial estável no início do estudo e após dez anos das intervenções. O cálculo da FEVE foi realizado pelos métodos de Teichholz ou bidimensional. RESULTADOS: Dos 611 pacientes integrantes do estudo MASS II, 422 pacientes estavam vivos ao término de 10,32 (±1,43) anos de seguimento; destes, 108 pacientes do grupo TM, 111 do RM e 131 do ATC realizaram reavaliação ecocardiográfica da função ventricular. As principais características demográficas, clínicas e angiográficas foram semelhantes nos 3 grupos, bem como a ocorrência de infarto agudo do miocárdico (IAM). A FEVE foi semelhante entre os grupos no início do estudo (0,61 + 0,07, 0,61 + 0,08 e 0,61 + 0,09, respectivamente, para os grupos ATC, RM e TM [p=0,675]) e ao término do seguimento (0,56 + 0,11, 0,55 + 0,11 e 0,55 + 0,12, respectivamente, para os grupos ATC, RM e TM [p=0,675]). Observou-se redução da função ventricular (p<0,001) nos três grupos terapêuticos de forma semelhante (p=0,641). Outras variáveis, como gênero, diabetes, idade, padrão arterial, necessidade de ATC ou RM adicionais, não influenciaram a evolução da FEVE. Porém, a ocorrência de IAM foi responsável por acentuada queda da FEVE (delta de decréscimo de 18,29 + 21,22% e 6,63 + 18,91% para pacientes com e sem IAM, respectivamente [p=0,001]). Além disso, a presença de IAM prévio à randomização e IAM durante o seguimento foram associadas a desenvolvimento de disfunção ventricular, definida como FEVE < 45%. CONCLUSÃO: Pacientes do grupo clínico portadores de DAC multiarterial desprotegida pelas estratégias de revascularização não apresentaram prejuízo adicional na função ventricular em comparação ao observado nos grupos cirúrgico e angioplastia. Além disso, qualquer que tenha sido a estratégia terapêutica aplicada, a função ventricular permaneceu preservada na ausência de infarto agudo do miocárdio / BACKGROUND: Historically, myocardial revascularization procedures, either by coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI), are assumed as effective therapeutic options for the protection of the ischemic myocardium. However, it is not established if those procedures are responsible for left ventricular function preservation, or even if their absence may contribute for the deterioration of left ventricular ejection fraction (LVEF). OBJECTIVES: to evaluate the evolution of LVEF in patients with chronic multivessel coronary heart disease and left ventricular function initially preserved, submitted to CABG, PCI or medical treatment (MT), after ten years of follow-up (MASS II substudy). METHODS: Transthoracic echocardiography was performed in patients with multivessel coronary heart disease, participants of MASS II trial, previously to randomization for one of the three possible therapeutic strategies (CABG, PCI and MT), and after 10 years of follow-up. LVEF was measured by the biplane method (Simpson) or alternatively by the Teichholz method. RESULTS: Of the 611 patients participants of MASS II trial, 422 were alive after a follow-up of 10.32 (±1.43) years. 350 had LVEF reassessed: 108 patients in MT group, 111 in CABG group and 131 in PCI group. Main baseline characteristics were similar among the three groups, including demographic, angiographic and laboratorial findings. The occurrence of acute myocardial infarction (AMI) was also similar among the 3 groups. There was no difference of LVEF either at the beginning (0.61 + 0.07, 0.61 + 0.08 e 0.61 + 0.09 respectively for PCI, CABG and MT, p=0.675) and the end of follow up (0.56 + 0.11, 0.55 + 0.11 e 0.55 + 0.12 respectively for PCI, CABG and MT groups, p=0.675). However, there was a slight, but significant reduction (P<0.001) of LVEF, similar on the three therapeutic groups (p=0.641). The impact of other variables over LVEF evolution, such as gender, age, diabetes, arterial pattern (including, left anterior descending coronary artery commitment) and additional revascularization, were also analyzed, with no influence on the evolution of LVEF. However, the presence of previous AMI (OR 2.50, 95% CI 1.40-4.45; p= 0.0007) and the occurrence of AMI during follow up (OR 2.73, 95% IC 1.25- 5.92; p=0.005) were associated with an increased risk of developing LVEF < 45%. Also, AMI during follow-up was responsible for a greater reduction of LVEF (reduction delta of 18.29 ± 21.22% and 6.63 ± 18.91%, respectively for patients with and without AMI during follow-up, p=0.001). CONCLUSION: Compared with PCI or CABG, the Medical group, with unprotected coronary disease by mechanical revascularization, showed no differences in left ventricular function after 10 years of follow-up. Moreover, regardless of therapeutic strategy applied, ventricular function remained preserved without AMI

O fitoterápico CATUAMA, utilizado no Brasil há mais de 20 anos, e seu extrato isolado T catigua apresentam efeito de reversão e prevenção da fibrilação ventricular (FV). FV, em pacientes com disfunção cardíaca, representa uma importante causa de morte súbita no mundo ocidental. Neste contexto, os efeitos de CATUAMA sobre a função cardíaca e os parâmetros hemodinâmicos foram investigados em ratos normais. Várias concentrações (10 a 800 ?g/mL) de CATUAMA (uma mistura dos extratos das plantas Trichilia Catigua, Paullinia Cupana, Ptychopetalum Olacoide e Zingiber Officinale) e de cada um de seus constituintes foram infundidas em preparações de músculos papilares isolados. A tensão desenvolvida (TD), tensão de relaxamento (TR) e as velocidades de aumento e redução da tensão (dT/dtmax e dT/dtmin) foram analisadas. Uma única dose de 200 ?g/mL foi injetada na veia jugular direita in situ. Os índices (dP/dtmax e dP/dtmin) de função ventricular esquerda (VE), as pressões sistólica (PSVE) e diastólica final (PDFVE), de perfusão coronariana (PPC), arteriais sistólica (PAS), diastólica (PAD) e média (PAM) e a frequência cardíaca (FC) foram monitoradas por 10min via cateterização VE. CATUAMA afetou a contratilidade miocárdica na maior dose (dose tóxica), reduzindo 9% a TD e 16% a TR, aumentando 90% a dT/dtmin. CATUAMA também melhorou em até 16% as PAS, PAD, PAM e PPC. Seus extratos isolados apresentaram efeitos diferenciados. T catigua não interferiu nas variáveis. P cupana reduziu a contratilidade e a PDFVE e aumentou os parâmetros hemodinâmicos assim como CATUAMA. P olacoide reduziu a TD, a TR e a PDFVE. Z officinale também reduziu a TD e a TR. CATUAMA e T catigua não trazem prejuízo à função cardíaca. / The Brazilian herbal medicine CATUAMA and its extract T catigua have shown reversion and prevention action on ventricular fibrillation (VF). VF, in patients with cardiac dysfunction, is an important cause of sudden death in Western world. In this regard, CATUAMA effects on cardiac function and hemodynamic parameters in normal rats were investigated. Various concentrations (10 to 800?g/mL) of CATUAMA (a mixture of Trichilia Catigua, Paullinia Cupana, Ptychopetalum Olacoide and Zingiber Officinale) and each herbal extract were infused into isolated papillary muscle bath. Developed tension (DT), tension at rest (RT) and velocities of increase and decrease tension (dT/dtmax and dT/dtmin) were analyzed. A single 200?g/mL dose was injected into jugular vein in situ. Left ventricular (LV) function index (dP/dtmax and dP/dtmin), LV systolic and end-diastolic pressures (LVSP and LVEDP), coronary driving pressure (CDP), systolic, diastolic and mean blood pressures (SBP, DBP and MBP) and heart rate (HR) were monitored during 10min by LV catheterization. CATUAMA affected myocardium contractility in the higher and toxic dose, decreasing 9% DT and 16% TR and increasing 90% dT/dtmin. CATUAMA also improved 16% SBP, DBP, MBP and CDP. Its isolated extracts showed different actions. T catigua demonstrated no interference in the variables. P cupana decreased contractility and LVEDP. It improved hemodynamic parameters as CATUAMA. P olacoide decreased DT, TR and LVEDP. Z officinale also decreased DT and TR. CATUAMA and T catigua did not affect cardiac function. These are important results for development of a new drug to prevent and to reverse VF without heart function impairment.

Estudos experimentais envolvendo animais diabéticos submetidos ao infarto do miocárdio (IM) ainda são bastante controversos no que diz respeito às respostas do coração diabético à injúria isquêmica. Neste sentido, o objetivo do presente estudo foi avaliar o efeito do IM experimental nas alterações ventriculares, cardio-respiratórias e autonômicas de ratos diabéticos por estreptozotocina. Foram utilizados ratos Wistar machos (230 a 260g) divididos em 4 grupos experimentais: controle (C, n=8), diabético (D, n=8), infartado (I, n=8) e diabético/infartado (DI, n=8). Após 15 dias de indução do diabetes (DM) por estreptozotocina (STZ) ou injeção de tampão citrato foi realizada a ligadura da artéria coronária esquerda nos grupos I e DI. Foram realizadas medidas do consumo máximo de oxigênio (VO2máx) e glicemia aos 15, 30, 60 e 90 dias de protocolo. Após 1 a 2 dias do IM (inicial) e aos 90 dias (final) de protocolo foram realizadas avaliações ecocardiográficas. A partir dos 90 dias de protocolo foram realizados registros diretos da pressão arterial (PA) e avaliações da sensibilidade barorreflexas, da modulação autonômica cardiovascular (variabilidade da freqüência cardíaca e da PA sistólica) e da função ventricular pela cateterização do ventrículo esquerdo (VE), bem como medidas da expressão das proteínas cardíacas relacionadas à homeostasia do Ca2+ intracelular por Western blot. Os grupos diabéticos (D e DI) apresentaram aumento da glicemia e redução do peso corporal, da PA e da freqüência cardíaca quando comparados com os grupos não diabéticos (C e I). O VO2 máx. estava reduzido no grupo D em relação ao grupo C e também nos grupos infartados (I e DI) quando comparados aos grupos não infartados (C e D) em todos os tempos avaliados. A área de IM foi semelhante entre os grupos infartados no início (~40±3%) e no final do protocolo (~45±5%). A área do IM, o eixo maior do VE e área do VE na diástole foram maiores na avaliação final em relação à avaliação inicial no grupo I, sendo que essas diferenças não foram observadas no grupo DI. A cavidade do VE e a massa do VE estavam aumentadas nos grupos I e DI em relação aos grupos C e D na avaliação final. O grupo DI apresentou atenuada disfunção sistólica nas avaliações finais (invasivas e não invasivas) quando comparado com I (fração de ejeção: DI=55±5% vs. I=42±3%; velocidade de encurtamento circunferencial: DI=43±1 vs. I=34±2 circ/s 10-4; derivada de contração do VE: DI=5.402±752 vs. I=4.642±457 mmHg/seg). Os grupos D, I e DI apresentaram disfunção diastólica, avaliada pelos tempos de relaxamento isovolumétrico e de desaceleração da onda E, quando comparados com o grupo C. Adicionalmente, a pressão diastólica final e o índice de desempenho miocárdico estavam aumentados nos grupos infartados (I e DI) em relação ao grupo C (5±0,3 mmHg e 0,39±0,01), mas reduzidos no grupo DI (12±3 mmHg e 0,45±0,01, respectivamente) em relação ao grupo I (20±2 mmHg e 0,57±0,04, respectivamente). Nas avaliações moleculares, o grupo DI apresentou aumento da razão SERCA2/trocador Na+/Ca2+ (48%), expressão de fosfolambam fosforilado na serina 16 (187%) e treonina 17 (243%), bem como redução da expressão do trocador Na+/Ca2+ (-164%), fosfolambam (-119%) e da proteína fosfatase 1 (-104%) em relação aos animais do grupo I. Disfunção autonômica, avaliada pela sensibilidade barorreflexa e pela variabilidade da FC (VFC) e da PA sistólica (VPAS), foram observadas nos grupos D, I e DI em relação ao grupo C. Apesar da melhor função sistólica e do perfil molecular das proteínas relacionadas à homeostase do Ca+2 intracelular, o grupo DI apresentou maior disfunção autonômica quando comparado com o grupo I, evidenciado pela menor sensibilidade barorreflexa (índice de bradicardia reflexa), pela reduzida VFC nos domínios do tempo (SDNN) e da freqüência (banda de baixa freqüência do intervalo de pulso), bem como pela exacerbada redução do componente de baixa freqüência da VPAS. Ao final dos 90 dias de protocolo a mortalidade foi semelhante entre os grupos I (63%) e DI (74%). Dessa forma, os resultados obtidos no presente trabalho fornecem evidências de que a presença de diabetes atenua a clássica disfunção ventricular (sistólica, diastólica e global) induzida pela isquemia miocárdica em ratos normais, o que pode estar associado a alterações compensatórias nas proteínas relacionadas à homeostase do cálcio intracelular. Por outro lado, a associação entre diabetes e infarto do miocárdio induz exacerbação da disfunção autonômica cardiovascular observada nos ratos somente diabéticos ou infartados. Estes achados, em conjunto, sugerem que a disfunção autonômica, mesmo em presença de um menor comprometimento da estrutura e funções ventriculares, possa ter contribuído para a mortalidade semelhante entre o grupo somente infartado e o grupo diabético infartado, o que reforça a importância do controle autonômico cardiovascular no prognóstico de indivíduos portadores de diabetes. / Experimental studies in diabetic animals submitted to myocardial infarction (MI) remain controversial in regard to the cardiac responses to ischemic injury. Therefore, the aim of the present study was to evaluate the effect of experimental MI on ventricular, cardiorespiratory and autonomic abnormalities in streptozotocin (STZ) diabetic rats. Male Wistar rats (230-260g) were randomly assigned to 4 experimental groups: control (C, n=8), diabetic (D, n=8), infarcted (I, n=8) and diabetic/infarcted (DI, n=8). After 15 days of diabetes induction by streptozotocin or citrate buffer injection, I and DI animals were submitted to left coronary occlusion. Maximal oxygen uptake (VO2 max) and blood glucose were evaluated on days 15, 30, 60 and 90. Echocardiographic evaluations were performed on days 1 or 2 (initial) and 90 (final) after MI. At the end of the experimental protocol (90 days), arteria pressure (AP), baroreflex sensitivity, cardiovascular autonomic modulation (heart rate variability and systolic arterial pressure variability), ventricular function and the expression of cardiac proteins involved with intracelular Ca2+ homeostasis were evaluated by Western blot. Diabetic groups (D and DI) presented higher blood glucose and lower body weight and heart rate than non-diabetic groups (C and I). VO2 max. was reduced on D group as compared with C group, as well as in infarcted groups (I and DI) as compared with non-infarcted ones (C and D). MI area was similar between all infarcted groups at the beginning (~40±3%) and at the end of experimental protocol (~45±5%). However, I group presented greater MI area, long-axis of left ventricle (LV) and diastolic LV area at the final evaluation when compared to the initial period, but these adaptations were not observed on DI group. LV cavity and mass were enhanced in I and DI groups compared with C and D groups at the end of experimental protocol. Systolic dysfunction was attenuated in DI group at the end of experimental protocol as compared with I group (ejection fraction: DI=55±5% vs. I=42±3%; velocity of circumferential fiber shortning: DI=43±1 vs. I=34±2 circ/sec 10-4; maximum rate of LV pressure rise (+dP/dt): DI=5.402±752 vs. I=4.642±457 mmHg/sec). D, I e DI groups presented diastolic dysfunction, evidenced by isovolumetric relaxation time and E wave deceleration, as compared with C group. LV end diastolic pressure and myocardial performance index were higher in infarcted groups (I and D) than in C group (5±0.3 mmHg and 0.39±0.01), but they were reduced in DI group (12±3 mmHg and 0.45±0.01, respectively) compared with I group (20±2 mmHg and 0.57±0.04, respectively). DI animals presented higher SERCA2/Na+-Ca2+ exchanger ratio (48%), higher phosphorylated phospholamban at Serine 16 (187%) and at Threonine 17 (243%), and lower expression levels of Na+-Ca2+ exchanger (-164%), phospholamban (-119%) and phosphatase protein 1 (-104%) than I group. Autonomic dysfunction, evaluated by baroreflex sensitivity and by heart rate variability (HRV) and systolic AP variability (APV), was observed in D, I and DI groups, compared with C group. Despite it was observed an improvement on systolic function and on molecular profile of intracellular Ca+2 proteins homeostasis, DI group presented greater autonomic dysfunction as compared with I group, verified by reduced baroreflex sensitivity (bradycardic reflex index), reduced HRV on time (SDNN) and frequency domains (low frequency band of pulse interval), as well as by the marked reduction on low frequency component of APV. At the end of experimental protocol (90 days), mortality was similar between I (63%) and DI (74%) groups. Thus, the results of this study show that diabetes attenuates the classic ventricle dysfunction (systolic, diastolic and global) induced by myocardial ischemia in normal rats. This adaptation might be related with compensatory alterations in proteins involved in the intracellular calcium homeostasis. On the other hand, the association of diabetes and MI was shown to worsen the cardiovascular autonomic dysfunction observed in diabetic or infarcted rats. Together, these findings suggest that the autonomic dysfunction, even in presence of reduced damage in ventricle and structure function, could have contributed to the similar mortality between infarcted and diabetic infarcted groups, reinforcing the importance of cardiovascular autonomic control in the prognosis of diabetic patients.

O fitoterápico CATUAMA, utilizado no Brasil há mais de 20 anos, e seu extrato isolado T catigua apresentam efeito de reversão e prevenção da fibrilação ventricular (FV). FV, em pacientes com disfunção cardíaca, representa uma importante causa de morte súbita no mundo ocidental. Neste contexto, os efeitos de CATUAMA sobre a função cardíaca e os parâmetros hemodinâmicos foram investigados em ratos normais. Várias concentrações (10 a 800 ?g/mL) de CATUAMA (uma mistura dos extratos das plantas Trichilia Catigua, Paullinia Cupana, Ptychopetalum Olacoide e Zingiber Officinale) e de cada um de seus constituintes foram infundidas em preparações de músculos papilares isolados. A tensão desenvolvida (TD), tensão de relaxamento (TR) e as velocidades de aumento e redução da tensão (dT/dtmax e dT/dtmin) foram analisadas. Uma única dose de 200 ?g/mL foi injetada na veia jugular direita in situ. Os índices (dP/dtmax e dP/dtmin) de função ventricular esquerda (VE), as pressões sistólica (PSVE) e diastólica final (PDFVE), de perfusão coronariana (PPC), arteriais sistólica (PAS), diastólica (PAD) e média (PAM) e a frequência cardíaca (FC) foram monitoradas por 10min via cateterização VE. CATUAMA afetou a contratilidade miocárdica na maior dose (dose tóxica), reduzindo 9% a TD e 16% a TR, aumentando 90% a dT/dtmin. CATUAMA também melhorou em até 16% as PAS, PAD, PAM e PPC. Seus extratos isolados apresentaram efeitos diferenciados. T catigua não interferiu nas variáveis. P cupana reduziu a contratilidade e a PDFVE e aumentou os parâmetros hemodinâmicos assim como CATUAMA. P olacoide reduziu a TD, a TR e a PDFVE. Z officinale também reduziu a TD e a TR. CATUAMA e T catigua não trazem prejuízo à função cardíaca. / The Brazilian herbal medicine CATUAMA and its extract T catigua have shown reversion and prevention action on ventricular fibrillation (VF). VF, in patients with cardiac dysfunction, is an important cause of sudden death in Western world. In this regard, CATUAMA effects on cardiac function and hemodynamic parameters in normal rats were investigated. Various concentrations (10 to 800?g/mL) of CATUAMA (a mixture of Trichilia Catigua, Paullinia Cupana, Ptychopetalum Olacoide and Zingiber Officinale) and each herbal extract were infused into isolated papillary muscle bath. Developed tension (DT), tension at rest (RT) and velocities of increase and decrease tension (dT/dtmax and dT/dtmin) were analyzed. A single 200?g/mL dose was injected into jugular vein in situ. Left ventricular (LV) function index (dP/dtmax and dP/dtmin), LV systolic and end-diastolic pressures (LVSP and LVEDP), coronary driving pressure (CDP), systolic, diastolic and mean blood pressures (SBP, DBP and MBP) and heart rate (HR) were monitored during 10min by LV catheterization. CATUAMA affected myocardium contractility in the higher and toxic dose, decreasing 9% DT and 16% TR and increasing 90% dT/dtmin. CATUAMA also improved 16% SBP, DBP, MBP and CDP. Its isolated extracts showed different actions. T catigua demonstrated no interference in the variables. P cupana decreased contractility and LVEDP. It improved hemodynamic parameters as CATUAMA. P olacoide decreased DT, TR and LVEDP. Z officinale also decreased DT and TR. CATUAMA and T catigua did not affect cardiac function. These are important results for development of a new drug to prevent and to reverse VF without heart function impairment.

A gordura epicárdica é biologicamente ativa e sua espessura nos obesos é aumentada. A repercussão da gordura epicárdica sobre o remodelamento cardíaco ainda não está completamente elucidada. No presente estudo, foi avaliada a gordura epicárdica e sua influência no remodelamento cardíaco de obesos mórbidos, antes e após a cirurgia bariátrica. Métodos: No Hospital das Clínicas da Universidade de São Paulo, foram recrutados de forma prospectiva 20 obesos mórbidos sem outras comorbidades e 20 controles. Os participantes realizaram avaliação clínica e laboratorial, medida da duração da onda P no ECG e ecocardiograma transtorácico. O grupo de obesos repetiu essa avaliação 12 meses após a cirurgia bariátrica. A medida da gordura epicárdica foi feita pelo ecocardiograma. Para comparar as variáveis contínuas, foram utilizados os testes t de Student (não pareado e pareado), de Mann-Whitney ou de Wilcoxson. Para definir correlação entre as variáveis lineares, foi utilizado o coeficiente de correlação de Pearson. Para definir a associação entre variáveis categóricas, foi usado o teste exato de Fisher. Para avaliar a associação entre variáveis dependentes e independentes, foi realizada uma análise de regressão múltipla. Os dados foram examinados no software R. Um valor de p abaixo de 0,05 foi considerado significativo. Resultados: No préoperatório, foram observados níveis elevados de proteína C reativa, uma maior duração da onda P, da massa ventricular e do diâmetro do átrio esquerdo nos obesos em relação aos controles (p < 0,05). Uma menor fração de ejeção do ventrículo esquerdo foi observada no grupo de obesos (p < 0,05). A gordura epicárdica foi maior nos obesos (p < 0,01). Uma correlação positiva foi encontrada entre a gordura epicárdica, a duração da onda P (r=0,70; p < 0,01), o diâmetro do átrio esquerdo (r=0,67; p < 0,01) e a massa ventricular (r=0,58; p < 0,01). Uma correlação inversa foi observada entre a gordura epicárdica e a fração de ejeção do ventrículo esquerdo (r=- 0,52; p < 0,01). Na análise de regressão múltipla, a gordura epicárdica permaneceu correlacionada com a duração da onda P, o diâmetro do átrio esquerdo e a fração de ejeção do ventrículo esquerdo (p < 0,05). Em 60% dos obesos, foi identificada alguma alteração na geometria ventricular. Uma associação entre a espessura da gordura epicárdica maior ou igual a 3,7 mm e a presença de remodelamento ventricular geométrico foi demonstrada (p=0,03). No pós-operatório, observou-se uma redução do índice de massa corporal, da proteína C reativa e da gordura epicárdica (p < 0,01). Uma redução da duração da onda P e um aumento da fração de ejeção do ventrículo esquerdo também foram observados (p < 0,01). Na análise de regressão múltipla esses achados permaneceram correlacionados à redução da gordura epicárdica (p < 0,05), independente da variação do índice de massa corporal e da proteína C reativa. Conclusões: Em obesos mórbidos sem outras comorbidades, a gordura epicárdica foi associada a um aumento da duração da onda P, do diâmetro do átrio esquerdo e da massa ventricular, além de uma menor fração de ejeção do ventrículo esquerdo. A espessura da gordura epicárdica igual ou acima de 3,7 mm foi associada a alterações do remodelamento ventricular. A redução da gordura epicárdica após a cirurgia bariátrica foi associada com a redução da duração da onda P e o aumento da fração de ejeção do ventrículo esquerdo, independente da variação do índice de massa corporal e da proteína C reativa / Epicardial fat is biologically active and its thickness is increased in obese subjects. The effects of epicardial fat on cardiac remodeling are still not fully understood. In the present study we evaluated epicardial fat and its influence on cardiac remodeling of morbidly obese, before and after bariatric surgery. Methods: We prospectively recruited 20 morbid obese subjects without other comorbidities and 20 control subjects at Hospital das Clínicas, Universidade de São Paulo. Participants underwent clinical and laboratory assessment, measure of P-wave duration on ECG and transthoracic echocardiogram. The obese group repeated this evaluation 12 months after the bariatric surgery. To compare continuous variables, we used t Student test (paired and nonpaired), Mann-Whitney and Wilcoxson tests. To define the correlation between linear variables we used Pearson correlation coefficient. To define the association between categorical variables we used Fisher exact test. A multiple regression analysis was performed to assess the association between dependent and independent variables. Data were analyzed by software R. A p value below 0.05 was considered statistically significant. Results: Preoperatively, we observed high levels of C-reactive protein, longer P-wave duration, larger ventricular mass and left atrial diameter in obese subjects compared to the controls (p < 0.05). Lower left ventricle ejection fraction was observed in the obese group (p < 0.05). Epicardial fat was higher among obese subjects (p < 0.01). A positive correlation was found between epicardial fat and P-wave duration (r=0.70; p < 0.01), left atrial diameter (r=0.67; p < 0.01), and ventricular mass (r=0.58; p < 0.01). An inverse correlation was observed between epicardial fat and left ventricle ejection fraction (r=-0.52; p < 0.01). In the multiple regression analysis, epicardial fat remained correlated with P-wave duration, left atrial diameter and left ventricle ejection fraction (p < 0.05). In 60% of the obese subjects, there was some abnormality in ventricular geometry. We showed association between thickness of epicardial fat equal to or higher than 3.7 mm and presence of geometric ventricular remodeling (p=0.03). Postoperatively, we observed reduction in body mass index, C-reactive protein and epicardial fat (p < 0.01). Reduction in P-wave duration and an increase in left ventricle ejection fraction were also observed (p < 0.01). In the multiple regression analysis, these findings were correlated with reduction in epicardial fat (p < 0.05), regardless of the variation in body mass index and C-reactive protein. Conclusion: In morbid obese subjects without other comorbidities, epicardial fat was associated with increase in P-wave duration, left atrial diameter and ventricular mass, in addition to smaller left ventricle ejection fraction. Epicardial fat thickness equal to or greater than 3.7 mm was associated with abnormalities in ventricular remodeling. Reduction of epicardial fat after bariatric surgery was associated with reduction of P-wave duration and increase in left ventricle ejection fraction, regardless of the variation in body mass index and C-reactive protein

Estudos experimentais envolvendo animais diabéticos submetidos ao infarto do miocárdio (IM) ainda são bastante controversos no que diz respeito às respostas do coração diabético à injúria isquêmica. Neste sentido, o objetivo do presente estudo foi avaliar o efeito do IM experimental nas alterações ventriculares, cardio-respiratórias e autonômicas de ratos diabéticos por estreptozotocina. Foram utilizados ratos Wistar machos (230 a 260g) divididos em 4 grupos experimentais: controle (C, n=8), diabético (D, n=8), infartado (I, n=8) e diabético/infartado (DI, n=8). Após 15 dias de indução do diabetes (DM) por estreptozotocina (STZ) ou injeção de tampão citrato foi realizada a ligadura da artéria coronária esquerda nos grupos I e DI. Foram realizadas medidas do consumo máximo de oxigênio (VO2máx) e glicemia aos 15, 30, 60 e 90 dias de protocolo. Após 1 a 2 dias do IM (inicial) e aos 90 dias (final) de protocolo foram realizadas avaliações ecocardiográficas. A partir dos 90 dias de protocolo foram realizados registros diretos da pressão arterial (PA) e avaliações da sensibilidade barorreflexas, da modulação autonômica cardiovascular (variabilidade da freqüência cardíaca e da PA sistólica) e da função ventricular pela cateterização do ventrículo esquerdo (VE), bem como medidas da expressão das proteínas cardíacas relacionadas à homeostasia do Ca2+ intracelular por Western blot. Os grupos diabéticos (D e DI) apresentaram aumento da glicemia e redução do peso corporal, da PA e da freqüência cardíaca quando comparados com os grupos não diabéticos (C e I). O VO2 máx. estava reduzido no grupo D em relação ao grupo C e também nos grupos infartados (I e DI) quando comparados aos grupos não infartados (C e D) em todos os tempos avaliados. A área de IM foi semelhante entre os grupos infartados no início (~40±3%) e no final do protocolo (~45±5%). A área do IM, o eixo maior do VE e área do VE na diástole foram maiores na avaliação final em relação à avaliação inicial no grupo I, sendo que essas diferenças não foram observadas no grupo DI. A cavidade do VE e a massa do VE estavam aumentadas nos grupos I e DI em relação aos grupos C e D na avaliação final. O grupo DI apresentou atenuada disfunção sistólica nas avaliações finais (invasivas e não invasivas) quando comparado com I (fração de ejeção: DI=55±5% vs. I=42±3%; velocidade de encurtamento circunferencial: DI=43±1 vs. I=34±2 circ/s 10-4; derivada de contração do VE: DI=5.402±752 vs. I=4.642±457 mmHg/seg). Os grupos D, I e DI apresentaram disfunção diastólica, avaliada pelos tempos de relaxamento isovolumétrico e de desaceleração da onda E, quando comparados com o grupo C. Adicionalmente, a pressão diastólica final e o índice de desempenho miocárdico estavam aumentados nos grupos infartados (I e DI) em relação ao grupo C (5±0,3 mmHg e 0,39±0,01), mas reduzidos no grupo DI (12±3 mmHg e 0,45±0,01, respectivamente) em relação ao grupo I (20±2 mmHg e 0,57±0,04, respectivamente). Nas avaliações moleculares, o grupo DI apresentou aumento da razão SERCA2/trocador Na+/Ca2+ (48%), expressão de fosfolambam fosforilado na serina 16 (187%) e treonina 17 (243%), bem como redução da expressão do trocador Na+/Ca2+ (-164%), fosfolambam (-119%) e da proteína fosfatase 1 (-104%) em relação aos animais do grupo I. Disfunção autonômica, avaliada pela sensibilidade barorreflexa e pela variabilidade da FC (VFC) e da PA sistólica (VPAS), foram observadas nos grupos D, I e DI em relação ao grupo C. Apesar da melhor função sistólica e do perfil molecular das proteínas relacionadas à homeostase do Ca+2 intracelular, o grupo DI apresentou maior disfunção autonômica quando comparado com o grupo I, evidenciado pela menor sensibilidade barorreflexa (índice de bradicardia reflexa), pela reduzida VFC nos domínios do tempo (SDNN) e da freqüência (banda de baixa freqüência do intervalo de pulso), bem como pela exacerbada redução do componente de baixa freqüência da VPAS. Ao final dos 90 dias de protocolo a mortalidade foi semelhante entre os grupos I (63%) e DI (74%). Dessa forma, os resultados obtidos no presente trabalho fornecem evidências de que a presença de diabetes atenua a clássica disfunção ventricular (sistólica, diastólica e global) induzida pela isquemia miocárdica em ratos normais, o que pode estar associado a alterações compensatórias nas proteínas relacionadas à homeostase do cálcio intracelular. Por outro lado, a associação entre diabetes e infarto do miocárdio induz exacerbação da disfunção autonômica cardiovascular observada nos ratos somente diabéticos ou infartados. Estes achados, em conjunto, sugerem que a disfunção autonômica, mesmo em presença de um menor comprometimento da estrutura e funções ventriculares, possa ter contribuído para a mortalidade semelhante entre o grupo somente infartado e o grupo diabético infartado, o que reforça a importância do controle autonômico cardiovascular no prognóstico de indivíduos portadores de diabetes. / Experimental studies in diabetic animals submitted to myocardial infarction (MI) remain controversial in regard to the cardiac responses to ischemic injury. Therefore, the aim of the present study was to evaluate the effect of experimental MI on ventricular, cardiorespiratory and autonomic abnormalities in streptozotocin (STZ) diabetic rats. Male Wistar rats (230-260g) were randomly assigned to 4 experimental groups: control (C, n=8), diabetic (D, n=8), infarcted (I, n=8) and diabetic/infarcted (DI, n=8). After 15 days of diabetes induction by streptozotocin or citrate buffer injection, I and DI animals were submitted to left coronary occlusion. Maximal oxygen uptake (VO2 max) and blood glucose were evaluated on days 15, 30, 60 and 90. Echocardiographic evaluations were performed on days 1 or 2 (initial) and 90 (final) after MI. At the end of the experimental protocol (90 days), arteria pressure (AP), baroreflex sensitivity, cardiovascular autonomic modulation (heart rate variability and systolic arterial pressure variability), ventricular function and the expression of cardiac proteins involved with intracelular Ca2+ homeostasis were evaluated by Western blot. Diabetic groups (D and DI) presented higher blood glucose and lower body weight and heart rate than non-diabetic groups (C and I). VO2 max. was reduced on D group as compared with C group, as well as in infarcted groups (I and DI) as compared with non-infarcted ones (C and D). MI area was similar between all infarcted groups at the beginning (~40±3%) and at the end of experimental protocol (~45±5%). However, I group presented greater MI area, long-axis of left ventricle (LV) and diastolic LV area at the final evaluation when compared to the initial period, but these adaptations were not observed on DI group. LV cavity and mass were enhanced in I and DI groups compared with C and D groups at the end of experimental protocol. Systolic dysfunction was attenuated in DI group at the end of experimental protocol as compared with I group (ejection fraction: DI=55±5% vs. I=42±3%; velocity of circumferential fiber shortning: DI=43±1 vs. I=34±2 circ/sec 10-4; maximum rate of LV pressure rise (+dP/dt): DI=5.402±752 vs. I=4.642±457 mmHg/sec). D, I e DI groups presented diastolic dysfunction, evidenced by isovolumetric relaxation time and E wave deceleration, as compared with C group. LV end diastolic pressure and myocardial performance index were higher in infarcted groups (I and D) than in C group (5±0.3 mmHg and 0.39±0.01), but they were reduced in DI group (12±3 mmHg and 0.45±0.01, respectively) compared with I group (20±2 mmHg and 0.57±0.04, respectively). DI animals presented higher SERCA2/Na+-Ca2+ exchanger ratio (48%), higher phosphorylated phospholamban at Serine 16 (187%) and at Threonine 17 (243%), and lower expression levels of Na+-Ca2+ exchanger (-164%), phospholamban (-119%) and phosphatase protein 1 (-104%) than I group. Autonomic dysfunction, evaluated by baroreflex sensitivity and by heart rate variability (HRV) and systolic AP variability (APV), was observed in D, I and DI groups, compared with C group. Despite it was observed an improvement on systolic function and on molecular profile of intracellular Ca+2 proteins homeostasis, DI group presented greater autonomic dysfunction as compared with I group, verified by reduced baroreflex sensitivity (bradycardic reflex index), reduced HRV on time (SDNN) and frequency domains (low frequency band of pulse interval), as well as by the marked reduction on low frequency component of APV. At the end of experimental protocol (90 days), mortality was similar between I (63%) and DI (74%) groups. Thus, the results of this study show that diabetes attenuates the classic ventricle dysfunction (systolic, diastolic and global) induced by myocardial ischemia in normal rats. This adaptation might be related with compensatory alterations in proteins involved in the intracellular calcium homeostasis. On the other hand, the association of diabetes and MI was shown to worsen the cardiovascular autonomic dysfunction observed in diabetic or infarcted rats. Together, these findings suggest that the autonomic dysfunction, even in presence of reduced damage in ventricle and structure function, could have contributed to the similar mortality between infarcted and diabetic infarcted groups, reinforcing the importance of cardiovascular autonomic control in the prognosis of diabetic patients.

<p>Reduced performance of the left ventricle to eject blood – left ventricular systolic dysfunction (LVSD) – is a common predecessor of the heart failure syndrome. With or without symptoms, LVSD is associated with a poor prognosis. However, with adequate treatment, the development or progression of symptoms, the need for hospitalisation and mortality can all be reduced. In the present work, the occurrence of LVSD was evaluated by echocardiography in a community-based sample of 75-year-old men and women (n = 433). LVSD was a common condition, with a prevalence rate of 6.8%. In nearly half the participants with LVSD, there was no clinical evidence of heart failure.</p><p>Community-based screening for asymptomatic LVSD has been proposed as a strategy to reduce the incidence of heart failure. Because of the high costs and low availability, echocardiography is not a suitable screening tool. The plasma concentration of B-type natriuretic peptide (BNP) has been the most advocated screening tool. Another alternative is the standard 12-lead electrocardiogram (ECG). Both the ECG and BNP were effective in excluding LVSD in our 75-year-old community-based sample. However, compared with BNP, the ECG had considerably better specificity. In screening for LVSD, BNP had a diagnostic value in addition to the ECG, but only in individuals with abnormal ECGs.</p><p>The left ventricular ejection fraction (LVEF) measured by echocardiography is a well-established index for describing left ventricular systolic function. The wall motion index (WMI) and the amplitude of mitral annulus motion (MAM) are suggested as alternative echocardiographic methods. Compared with MAM, the WMI had a more favourable agreement with the LVEF in our 75-year-old participants. Nonetheless, MAM was a strong predictor of mortality. MAM predicted the risk of all-cause and cardiac mortality independently of other risk factors. In addition, when it came to cardiac mortality, the predictive ability of MAM was independent of the LV function measured as the WMI.</p>

Reduced performance of the left ventricle to eject blood – left ventricular systolic dysfunction (LVSD) – is a common predecessor of the heart failure syndrome. With or without symptoms, LVSD is associated with a poor prognosis. However, with adequate treatment, the development or progression of symptoms, the need for hospitalisation and mortality can all be reduced. In the present work, the occurrence of LVSD was evaluated by echocardiography in a community-based sample of 75-year-old men and women (n = 433). LVSD was a common condition, with a prevalence rate of 6.8%. In nearly half the participants with LVSD, there was no clinical evidence of heart failure. Community-based screening for asymptomatic LVSD has been proposed as a strategy to reduce the incidence of heart failure. Because of the high costs and low availability, echocardiography is not a suitable screening tool. The plasma concentration of B-type natriuretic peptide (BNP) has been the most advocated screening tool. Another alternative is the standard 12-lead electrocardiogram (ECG). Both the ECG and BNP were effective in excluding LVSD in our 75-year-old community-based sample. However, compared with BNP, the ECG had considerably better specificity. In screening for LVSD, BNP had a diagnostic value in addition to the ECG, but only in individuals with abnormal ECGs. The left ventricular ejection fraction (LVEF) measured by echocardiography is a well-established index for describing left ventricular systolic function. The wall motion index (WMI) and the amplitude of mitral annulus motion (MAM) are suggested as alternative echocardiographic methods. Compared with MAM, the WMI had a more favourable agreement with the LVEF in our 75-year-old participants. Nonetheless, MAM was a strong predictor of mortality. MAM predicted the risk of all-cause and cardiac mortality independently of other risk factors. In addition, when it came to cardiac mortality, the predictive ability of MAM was independent of the LV function measured as the WMI.

Background: Aortic stenosis (AS) is the most common heart valve disease in Europe and North America. Age-related calcification of the valve is the commonest cause of acquired AS, especially in patients older than 70 years.Conventional surgical aortic valve replacement (SAVR) and the novel, minimally invasive transcatheter aortic valve implantation (TAVI), effectively preserve left ventricular (LV) function, relieve symptoms and improve survival in patients with severe symptomatic AS. However, patients with impaired LV function may carry significant operative risk, and long recovery time. In addition, such patients might have other comorbidities, and hence adding another challenge. Thus evaluation of ventricular function before and after AVR, as well as critical evaluation of TAVI patients should contribute to better clinical outcome. Methods: We studied LV function by conventional echocardiography before and after SAVR in the following groups; (I) 86 patients (aged 71±10 years) with severe AS and LV dysfunction; (II) 112 consecutive elderly AS patients (aged 77±2 years) and compared them with 72 younger patients (aged 60±1 years); (III)66 patients (age 70±2 years, 53 male) who underwent AVR for severe AS with concurrent LV dysfunction; (IV) 89 consecutive patients with symptomatic severeAS who underwent successful TAVI, 45 of whom received trans-apical TAVI (TA)(age 80.8±4.9 year, 26 male) and 44 trans-femoral TAVI (TF) (age 82.9±5.8 year,22 male).The conventional echocardiographic measurements were made according to the guidelines. Severe AS was identified by aortic valve mean pressure gradient &gt;40mmHg or valve area &lt;1.0 cm2. LV systolic dysfunction was identified as ejection fraction (EF) &lt;50%. LV long-axis function was presented by mitral annular plane systolic excursion ( MAPSE ) at lateral wall and septal wall, which were measured from apical four-chamber view. Also from the same view, LV septal and lateral wall deformation using STE as well as global longitudinal systolic strain. The LV systolic twist as the net difference between apical rotation and basal rotation was measured from the parasternal apical and basal short-axis views in the TAVI patients. Results: Study I: In the low flow and high gradient group, operative (30-day) mortality was 10%, and peri-operative mortality was associated with lower mean LVEF, higher mitral E:A ratio, peak systolic pulmonary artery pressure (PSPAP), and higher serum creatinine (all p&lt;0.001), NYHA class III–IV, concomitant coronary artery bypass graft (CABG), urgent surgery, and longer bypass-time (all p&lt; 0.05). Mortality at 4 years was 17%. Univariate predictors of 4-year mortality were: lower EF (p&lt;0.001), presence of restrictive LV filling (p&lt;0.001), raised PSPAP (p&lt;0.001) and CABG (p=0.037). However, only EF&lt;40 % (p=0.03), the presence of restrictive LV filling (p=0.033) and raised PSPAP (p&lt;0.01)independently predicted mortality in this group.Study II: Elderly patients had higher NYHA class, more frequent atrial fibrillation (AF), coronary artery disease (CAD), emergency operation and use of bioprosthetic valves. They also had shorter E-wave deceleration time (DT) and larger left atria (LA) (p&lt;0.05 for all). 30-day mortality was 12% vs 4 % (Log Rank x2=3.02, p=0.08) and long term mortality was 18% vs 7% (Log Rank x2=4.38,p=0.04) in the two groups, respectively. Age was not related to mortality after adjustment for other variables. Among all variables, anemia (OR 4.20, CI:1.02–6.86, p=0.04), cardiopulmonary bypass (CPB) time (OR 1.02, CI 1.01–1.04,p&lt;0.01), significant patient prosthesis mismatch (PPM) (OR 5.43, CI 1.04–18.40,p&lt;0.05) were associated with 30-day mortality in elderly patients. Their long-term mortality was related to CBP time (OR 1.02, CI 1.00–1.05, p=0.04),PPM (OR 4.64, CI 1.33–16.11, p=0.02) and raised LA pressure: DT (OR 0.94, CI0.84–0.99, p=0.03) and pulmonary artery systolic pressure (PASP) (OR 1.12, CI1.03–1.19, p&lt;0.001).STUDY III: Following SAVR peak aortic pressure gradient (AOPG) decreased and indexed valve area increased (64±3 to 19±1 mmHg and 0.30±0.01 to 0.89±0.03 cm2/m2, p&lt;0.001 for both). LVEF increased (from 45±1 to 54±2%;p&lt;0.001), LV end diastolic and end-systolic dimensions fell (LVEDD index: from 33±1 to 30±1 mm/m2; and LVESD index: from 27±1 to 20±1 mm/m2; (p&lt;0.01 forboth). LV diastolic dysfunction improved as evidenced by the fall in E/A ratio (from 2.6±0.2 to 1.9±0.4) and prolongation of total filling time; (from 29.2±0.6 to31.4±0.5 s/min, p=0.01 for both). Among all echocardiographic variables, LV dimensions (LVEDD index, OR 0.70, CI 0.52–0.97, p&lt;0.05; LVESD index, OR 0.57, CI 0.40–0.85, p=0.005) were the two independent predictors of post-operative LV functional recovery on multivariate analysis. A cut-off value ofpre-operative LVESD index&lt;=27.5 mm/m2 was 85% sensitive and 72% specific inpredicting intermediate-term recovery of LV function after AVR (AUC, 0.72, p=0.002). STUDY IV: Before TAVI, there was no difference between the two patient groups in gender, age, body surface area (BSA) and baseline LV function. However, left ventricular mass index (LVMi), left atrial volume index (LAVi) and tricuspid regurgitation pressure drop (TRPdrop) were increased in the TA group (p&lt;0.05).One week after TAVI, aortic pressure gradient (AOPG) markedly dropped in thetwo groups (both p&lt;0.001), LVEDD index and LVESD index fell but EF andmyocardial strain remained unchanged. Overall cavity twist reduced (p&lt;0.048).Significant LVESD index reduction was only seen in TF group (p=0.02) with a slight increase in LVEF (p=0.04). Lateral MAPSE increased only in the TF group(p=0.02). LV longitudinal systolic strain remained unchanged in TA patients while apical lateral strain increased in TF group. LV apical rotation fell in the two groups but basal rotation increased only in the TA patients (p=0.02). LAVi reduced in bothgroups and to a greater extent in TF TAVI (p=0.006), as did TRPdrop (p&lt;0.001). Conclusion: SAVR and TAVI are two effective treatments for severe AS patients.The severity of pre-operative systolic and diastolic LV dysfunction is the major predictor of mortality following SAVR for low-flow and high gradient AS.Peri-operative AVR survival is encouraging in the elderly. Long term mortality in the elderly is related to PPM, LV diastolic dysfunction and secondary pulmonary hypertension. LV functional recovery was evident in most patients with LV dysfunction after SAVR. A lower prevalence of LV functional recovery in patients with large pre-operative LVESD index might signify the loss of contractile reserveand thus predict post-operative functional recovery. TAVI results in significant early improvement of segmental and overall ventricular function, particularly in patients receiving the trans-femoral approach. The delayed recovery of the trans-apical TAVI group, we studied, might reflect worse pre-procedural diastolic cavity function.