Haemodialysis (HD) patients have a high mortality risk and most have echocardiographic evidence of abnormal cardiac structure or function. Markers, such as left ventricular hypertrophy (LVH), show association with adverse outcome in the general population and can aid in clinical decision making. The aim of this research was to explore the prognostic utility of established and novel two-dimensional (2DE) and three-dimensional transthoracic echocardiographic (RT3DE) techniques in HD patients. Adult maintenance HD patients from a single tertiary nephrology centre including satellite dialysis units were enrolled. Exclusion criteria were if patients were clinically unstable, unable to consent, or if required ambulance transportation for echocardiography visits. Consented patients underwent 2DE with speckle tracking (STE), RT3DE and VicorderTm measurements of pulse wave velocity (PWV) on a non-dialysis day, after the short inter-dialytic break. Clinical phenotype data, 3-month averaged blood results and dialysis prescriptions were obtained from the hospital electronic patient records. All patients screened were followed-up until death, renal transplantation, moving out of the region, or 16th November 2015. Regression analysis was used to assess the cross-sectional relationship between echocardiographic parameters. Relationship of echocardiographic parameters with outcome was assessed by Cox regression analysis. The first study explored whether patients recruited had similar characteristics and survival compared with patients who declined consent or who were excluded from the study. Patients who declined consent had an adjusted hazard ratio (HR) for all-cause mortality compared with recruited patients of 1.70, 95% confidence interval (CI) 1.10-2.52, and excluded patients had an adjusted HR of 1.30, 95% CI 0.75-2.25. Recruited patients may be a 'fitter' population and this needs to be considered when interpreting results. The second study reports that when global longitudinal strain (GLS) is combined in a multivariable model with PWV; PWV is superior to GLS in its association with mortality (adjusted HR 1.23, 95% CI 1.03-1.47 versus HR 1.00, 95% CI 0.86-1.17). When this analysis was repeated in a sub-group of patients with LVH, neither GLS nor PWV were associated with mortality, whilst both were prognostically significant in a preserved LVEF sub-group (PWV: HR 1.23, 95% CI 1.04-1.4 and GLS: HR 1.16, 95% CI 1.01-1.33). Therefore GLS has different prognostic implications in different patient sub-groups. The third study explored whether tissue motion mitral annular displacement (TMAD) measured by STE may be a more useful alternative to GLS as it measures strain but is quicker and less user-dependent. TMAD was closely correlated to GLS (r=-0.614, p<0.001), but had no prognostic power for mortality (adjusted HR 1.04,95% CI 0.91-1.19). The correlation between 2DE and RT3DE determined LV mass and volume measurements and the prognostic significance of RT3DE measurements were assessed. Although there was good correlation between 2DE and RT3DE LV volume measurements, 2DE overestimated LV mass compared to RT3DE. RT3DE measures gave no added prognostic value, and there were added difficulties in obtaining adequate images for RT3DE (35% of patients who had adequate 2D images). Furthermore, although RT3DE determined LV mechanical dyssynchrony index was prolonged in HD patients compared with published general population controls, it failed to show any prognostic significance (HR 2.16, 95% CI 0.96-4.89) for mortality, but was associated with hospitalisation for heart failure (HR 1.03, 95% CI 1.00-1.06). These results indicate that novel measurements of sub-clinical cardiac dysfunction have the potential to aid prognostication in this high risk population. Follow-up studies exploring the longitudinal change in these parameters is ongoing.

No description available.

No description available.

No description available.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

No presente estudo, duas importantes situações foram abordadas no intuito de se melhor entender os mecanismos homeostáticos dos pressorreceptores na gênese da hipertrofia cardíaca em resposta à hipertensão renovascular: o efeito do tempo de clipe na artéria renal e o efeito dos níveis pressóricos e da variabilidade da pressão arterial. O curso temporal mostrou que, antes mesmo da instalação da hipertensão, há alteração da morfologia cardíaca, qual seja o desenvolvimento de uma hipertrofia ventricular excêntrica e, como forma de mecanismo compensatório, um aumento da expressão de algumas proteínas da homeostase do cálcio (fosfolambam fosforilada pela serina-16 e corrigido pelo fosfolambam total em 100% e fosfolambam fosforilado pela treonina-17 e corrigido pelo fosfolambam total em 54%). Uma vez instalada a hipertensão, observou-se um remodelamento ventricular esquerdo para o tipo concêntrico, com prejuízo da função diastólica e um desbalanço do sistema nervoso autonômico, com aumento da atividade simpática, observado pelo aumento da razão dos componentes de baixa freqüência (LF) e alta freqüência (HF) no tacograma (0,44 ± 0,10 vs. 0,20 ± 0,03 nos controles). A análise do efeito da pressão arterial e da variabilidade da pressão arterial mostrou uma correlação positiva com o grau de hipertrofia ventricular esquerda (r=0,76, p<0,01). A secção cirúrgica dos pressorreceptores somada à implantação do clipe na artéria renal mostrou adaptações cardiovasculares em níveis semelhantes (mesmo nível de hipertensão) e, por vezes maiores (modulação simpática para o coração e para os vasos, hipertrofia ventricular esquerda e disfunção diastólica), ao grupo cuja artéria renal foi estenosada e que permaneceu com os barorreceptores intactos. Estas respostas aconteceram num período de tempo três vezes menor na ausência do barorreflexo. Tais observações ressaltam o importante efeito homeostático do barorreflexo na gênese das respostas cardíacas adaptativas à hipertensão arterial / In the present study, two important situations were observed to evaluate the role of the baroreceptors in the genesis of cardiac hypertrophy in response to hypertension: the effect of the time-course of the clip in the renal artery and the effect of the level of arterial blood pressure (ABP) and blood pressure variability (ABPV). The time-course evaluation showed that even before hypertension was installed, cardiac alterations could be observed, as a left ventricular eccentric hypertrophy. Compensatory mechanisms, such as an increase in some calcium homeosthatic proteins, could also be noticed (increase in phosphorilated phospholmaban at threonin-17 corrected by total phospholamban in 54% and increase in phosphorilated phospholmaban at serine-16 corrected by total phospholamban in 100%). However, once hypertension was established, left ventricle morphology changed to a concentric hypertrophy, accompanied by a diastolic dysfunction and enhanced sympathetic modulation, observed by relation between low-frequency component (LF) and high-frequency component (HF) at tachogram (0,44 ± 0,10 vs. 0,20 ± 0,03 in control group). ABP and ABPV analyses showed an important positive correlation with the degree of left ventricular hypertrophy (r=0,76, p<0,01). However, the absence of baroreceptors in one of the hypertensive groups, evoked the same cardiovascular alterations (same level of hypertension) or even worse (sympathetic modulation for heart and vessels, left ventricular hypertrophy and diastolic dysfunction) reached by the hypertensive baroreceptors-preserved group. These cardiovascular responses were observed in a period that correspond one third of time to the group with intact baroreflex. These observations lead us to conclude the importance of homeosthatic effects of the baroreflex in the genesis of cardiac responses to hypertension

O remodelamento cardíaco é uma sequela da hipertensão. Receptores do tipo Toll (TLRs) pertencem a imunidade inata e sua ativação produz moléculas inflamatórias. O objetivo do trabalho foi avaliar a participação do TLR4 no remodelamento cardíaco de ratos espontaneamente hipertensos (SHR). Utilizamos SHR e Wistar de 6 e 21 semanas. O nível do RNAm do TLR4 de SHR de 21 semanas é maior em relação aos outros grupos. Outros grupos de Wistar e SHR de 19 semanas foram tratados com anticorpo anti-TLR4, os controles receberam anticorpo IgG inespecífico. Observamos redução no nível do RNAm do TLR4 e MyD88 e expressão protéica do TLR4, MyD88, TNF-<font face=\"symbol\">a e IL-1<font face=\"symbol\">b de SHR anti-TLR4 em relação aos SHR controle. Não houve alteração nos valores pressóricos. Verificamos redução no nível do RNAm de colágenos I e III, de metaloproteinases 2 e 9, de ANP, BNP e <font face=\"symbol\">a-actina esquelética e de deposição de colágeno, área e diâmetro de cardiomiócitos de SHR anti-TLR4 em relação aos SHR controle. Nossos resultados sugerem que o TLR4 participa do processo de remodelamento cardíaco de SHR adultos. / The cardiac remodeling is a sequel of hypertension. Toll-Like Receptors (TLR) are innate immunity receptor and its activation produces inflammatory molecules. The objective of this study was to evaluate the involvement of TLR4 in cardiac remodeling of spontaneously hypertensive rats (SHR). We used male Wistar and SHR with 6 and 21 weeks. The level of TLR4 mRNA in SHR with 21 weeks is higher than the other groups. Wistar and SHR with 19 weeks were treated with anti-TLR4 or nonspecific IgG antibody (control group). We observed a reduction in the level of TLR4 and MyD88 mRNA and protein expression of TLR4, MyD88, TNF-<font face=\"symbol\">a and IL-1<font face=\"symbol\">b in anti-TLR4 SHR compared to control SHR. There was no change in blood pressure values in SHR after anti-TLR4 treatment. We observed reduction in mRNA level of collagens I and III, metalloproteinases 2 and 9, ANP, BNP, <font face=\"symbol\">a-skeletal actin, collagen deposition, cardiomyocyte area and diameter in anti-TLR4 SHR compared to control SHR. Our results suggest that TLR4 participates of cardiac remodeling process in adults SHR.

No description available.

<p>Left ventricular hypertrophy (LVH) and the insulin resistance syndrome are common conditions associated with a markedly increased cardiovascular risk. In a fairly large prospective longitudinal study of men from the general population, we found that an unfavorable serum fatty acid profile and components of the insulin resistance syndrome such as dyslipidemia, obesity and hypertension at age 50 predicted the prevalence of LVH at age 70. In cross-sectional analyses at age 70, several components of the insulin resistancesyndrome were significantly related to left ventricular relative wall thickness and concentric remodeling, but less to LVH. Left ventricular relative wall thickness was inversely related to insulin sensitivity in skeletal muscle and borderline significantly directly related to insulin sensitivity in the myocardium in a healthy, normotensive sample of the cohort investigated with positron emission tomography, whereas left ventricular mass index was not related to myocardial or skeletal muscle insulin sensitivity. At age 70, echocardiographic LVH was related to a variety of common electrocardiographic diagnoses. In a prospective mortality analysis with baseline at age 70 and a median follow-up time of five years, echocardiographic and electrocardiographic LVH predicted mortality independently of each other and of other cardiovascular risk factors, implying that echocardiographic and electrocardiographic LVH in part carry different prognostic information.</p><p>In summary, components of the insulin resistance syndrome predicted LVH twenty years later, but were cross-sectionally more related to increased left ventricular relative wall thickness and concentric remodeling. Echocardiographic and electrocardiographic LVH predicted mortality independently of each other and of components of the insulin resistance syndrome.</p>

Left ventricular hypertrophy (LVH) and the insulin resistance syndrome are common conditions associated with a markedly increased cardiovascular risk. In a fairly large prospective longitudinal study of men from the general population, we found that an unfavorable serum fatty acid profile and components of the insulin resistance syndrome such as dyslipidemia, obesity and hypertension at age 50 predicted the prevalence of LVH at age 70. In cross-sectional analyses at age 70, several components of the insulin resistance syndrome were significantly related to left ventricular relative wall thickness and concentric remodeling, but less to LVH. Left ventricular relative wall thickness was inversely related to insulin sensitivity in skeletal muscle and borderline significantly directly related to insulin sensitivity in the myocardium in a healthy, normotensive sample of the cohort investigated with positron emission tomography, whereas left ventricular mass index was not related to myocardial or skeletal muscle insulin sensitivity. At age 70, echocardiographic LVH was related to a variety of common electrocardiographic diagnoses. In a prospective mortality analysis with baseline at age 70 and a median follow-up time of five years, echocardiographic and electrocardiographic LVH predicted mortality independently of each other and of other cardiovascular risk factors, implying that echocardiographic and electrocardiographic LVH in part carry different prognostic information. In summary, components of the insulin resistance syndrome predicted LVH twenty years later, but were cross-sectionally more related to increased left ventricular relative wall thickness and concentric remodeling. Echocardiographic and electrocardiographic LVH predicted mortality independently of each other and of components of the insulin resistance syndrome.