Left ventricular hypertrophy (LVH) and increases in large artery stiffness predict cardiovascular outcomes in patients with renal failure. What determines left ventricular mass index (LVMI) and large artery stiffness and the contribution toward LVH and large artery dysfunction is not entirely clear. Consequently, this cross sectional study was aimed at assessing the various factors impacting on LVH in haemodialysis (HD), to contribute toward our understanding of the pathophysiology of LVH and large artery dysfunction in 94 adult HD patients. Pre- and post-dialysis blood pressures (BPs) were determined over 12 sessions of dialysis and averaged. Pulse wave analysis performed at the carotid, femoral and radial arteries was employed to determine pulse wave velocity (PWV) and central augmentation index (AIc). Echocardiography was performed to determine left ventricular mass (LVM) indexed to body surface area (LVMI). Natriuretic peptides, procollagen type I c-peptide (PIP), c-terminal telopeptide of type I collagen (ICTP), matrix metalloproteinases and their inhibitors were studied. The prevalence of LVH was 72.8 % (67/92) .On multivariate analysis pre- (p≤ 0.005), post- (p<0.05) and averaged dialysis (p < 0.015) systolic BP were associated with LVMI and PWV. 24 hour (r = 0.260, p = 0.026), day (r = 0.247, p = 0.036), and night (r= 0.241, p = 0.042) systolic BP were not more closely associated with LVMI than the averaged dialysis systolic BP (r = 0.272, p = 0.010). Similarly 24 hour (r = 0.41, p = 0.0003), day (r=0.400, p = 0.0005), and night (r =0.416, p = 0.0003) systolic BP were not more closely associated with PWV than the post-dialysis systolic BP (r=0.39, p=0.0001) indicating that these BP measurements are as effective as 24-hour ambulatory BP in predicting cardiovascular target organ changes. No relationship between either PWV (r=-0.08), or AIc (r=-0.10) and LVMI, between PWV (r=-0.11), or AIc (r=0.03) and LV MWT was noted. IVCD was independently associated with LVMI (partial r adjusted for average dialysis SBP=0.27, p=0.014; partial r adjusted for 24-hour SBP=0.29, p=0.013), and LV mean wall thickness (p<0.01), but not with LV relative wall thickness (p=0.18), or LV end diastolic diameter (p=0.88). An association between IVCD and AIc (partial r adjusted for average dialysis SBP=0.21, p<0.05), but not PWV was noted. NT-proANP and NT-proBNP were independently associated with LVMI (p<0.0001) but neither were associated with IVCD independent of LVMI suggesting a close association with LVMI in HD. Serum concentrations of matrix metalloproteinases 1, 2 and 9, and their tissue inhibitors (1 and 2) were not associated with LVMI, remodelling or PWV and neither procollagen I nor the C-terminal telopeptide of type I collagen (ICTP) were associated with LVMI. Thus, factors impacting on LVH in this study were systolic BP, NT-proANP, NT-proBNP and IVCD.

Orientador: Silméia Garcia Zanati Silméia Garcia Bazan / Resumo: Fundamento: A hipertensão arterial sistêmica (HAS) é um dos principais fatores de risco para o desenvolvimento de doença cardiovascular. Quando a mulher hipertensa engravida, ocorre uma nova condição hemodinâmica, com adição da situação de sobrecarga crônica de pressão à situação de sobrecarga crônica de volume. Essa nova condição hemodinâmica pode propiciar maior hipertrofia miocárdica (HVE), sendo que sua evolução após o parto ainda é pouco estudada na literatura. Suspeita-se que as mulheres hipertensas que apresentaram HVE durante gestação mantenham essa alteração cardíaca após o parto. Objetivos: Avaliar a hipertrofia miocárdica em mulheres hipertensas no terceiro trimestre da gestação e após seis meses do parto e estabelecer quais variáveis clínicas estão associadas com risco aumentado de hipertrofia miocárdica. Métodos: Estudo prospectivo longitudinal incluindo 41 mulheres gestantes com idade gestacional acima de 35 semanas e com diagnóstico prévio de HAS, acompanhadas no Ambulatório de Pré-Natal de Hipertensão Arterial do Serviço de Obstetrícia do Hospital das Clínicas da Faculdade de Medicina de Botucatu - UNESP. Foram submetidas às avaliações clínica e ecocardiográfica em dois momentos, período gestacional e período de seis meses após o parto. A HVE foi definida para índice de massa do ventrículo esquerdo indexada pela altura (IMVE) ≥ 45g/m2,7. Análise estatística: regressão logística multivariada com as exposições mais fortemente associadas com a manutenção da HVE n... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Background: Systemic arterial hypertension (SAH) is one of the principal risk factors for developing cardiovascular disease. When a hypertensive woman becomes pregnant, a new hemodynamic condition is installed, with addition from chronic pressure overload to chronic volume overload. This new hemodynamic condition can provides greater myocardial hypertrophy (LVH), whose postpartum evolution has been little studied in the literature. It is suspected that hypertensive women who presented LVH during pregnancy maintain this cardiac alteration after delivery. Objectives: To evaluate myocardial hypertrophy in hypertensive women in the third trimester of pregnancy and six months after delivery and to establish which clinical variables are associated with elevated risk of myocardial hypertrophy. Methods: Prospective longitudinal study including 41 pregnant women beyond 35 gestational weeks and with previous SAH diagnosis, monitored at the Hypertension Clinic of the Obstetrics Unit of the Botucatu School of Medicine - UNESP. They were submitted to clinical and echocardiographic evaluation at two moments, the gestational period and six months postpartum. LVH was defined for the left ventricular mass index as (LVMI) ≥ 45g/m2.7. Statistical analysis: multivariate logistic regression with the exposures most strongly associated with maintenance of hypertrophy in univariate analysis. Significance level: p<0.05. Results: The mean age was 29±6.2 years; mean gestacional age was 36.7±1.18 weeks;... (Complete abstract click electronic access below) / Mestre

Heart failure due to ischemic and dilated cardiomyopathy is a large and expanding public health problem, and ventricular arrhythmias are a common and potentially fatal complication of this condition. Despite extensive investigation, the mechanisms of ventricular arrhythmias in cardiomyopathy remain incompletely understood. This thesis examines these mechanisms, particularly with reference to the potential role of the underlying electrophysiologic substrate. It also evaluates the validity and utility of some of the tools commonly used to assist in the mapping and catheter ablation of ventricular arrhythmias. / The central rationale of this thesis is that the mechanisms of ventricular arrhythmogenesis in cardiomyopathy are optimally studied by comparing ischemic and dilated cardiomyopathy patients with spontaneous (rather than inducible) ventricular tachycardia to otherwise similar heart failure patients who have never developed clinical arrhythmias. This has been done in the two largest projects herein. In the setting of ischemic cardiomyopathy, it is demonstrated that there are large differences in the electrophysiologic substrate between the groups such that patients with clinical ventricular tachycardia have substantially greater endocardial scarring as inferred by the presence of low-voltage zones and scar-related electrograms compared to control cardiomyopathy patients with no spontaneous arrhythmias. Furthermore, there appear to be fundamental differences in the nature of the scarring process with ventricular tachycardia patients having more abnormal electrograms per unit area of low-voltage and more scar-related putative conducting channels (which may form critical diastolic isthmuses in tachycardia). / This was accompanied by a lower rate of ventricular tachycardia inducibility in the control patients. Taken together these findings point to a major role for the electrophysiologic substrate in ventricular arrhythmogenesis in the setting of ischemic cardiomyopathy. The situation in dilated cardiomyopathy is more complicated and although significant endocardial substrate differences were again seen in this context, there was marked heterogeneity in the group with ventricular tachycardia with some patients having extensive low-voltage zones and others having normal endocardial voltage. As the pericardium could not be accessed for ethical reasons in control patients with no clinical arrhythmia, the precise role of an abnormal epicardial substrate was not able to be defined in this study. Another project in this thesis examines potential improvements (in the form of a multielectrode mapping catheter) to a widely used electroanatomic mapping system that can assist in mapping ventricular tachycardia circuits and the substrates underlying them. A further project compares magnetic resonance imaging and electroanatomic substrate mapping in defining ventricular scarring in the context of cardiomyopathy. And finally, electroanatomic mapping is used to look at endocardial activation patterns and electrical dyssynchrony in cardiomyopathy patients with and without left bundle branch block. The demonstrated variability in these factors may underlie the significant non-response rates to cardiac resynchronization therapy. / In summary, it is apparent from this work that the electrophysiologic substrate plays a crucial role in mechanism of the ventricular arrhythmias seen in heart failure patients with ischemic and dilated cardiomyopathy. An improved understanding of these mechanisms may in turn lead to better diagnosis, risk stratification and ultimately management of heart failure patients suffering from, or at risk of developing these potentially lethal arrhythmias.

The right ventricle (RV) of the heart is clearly an extremely important component of cardiovascular function and physiology. The RV is affected in many cardiovascular disease processes, including pulmonary arterial hypertension (PAH), congenital heart disease, and left ventricular failure. In PAH, the performance of the RV is the strongest predictor of morbidity and mortality. Several advances in PAH therapies have occurred over the past decade, including the use of phosphodiesterase-5 (PDE5) inhibitors, endothelin receptor antagonists (ETRAs), and experimental metabolic modulators (Dichloroacetate-DCA). Most therapies for PAH are focused on decreasing RV afterload by vasodilation of the pulmonary vasculature, though there is a surprising lack of focus on direct effects of therapies on the RV. In PAH, the RV compensates to the increase in afterload by hypertrophy, this hypertrophic defense mechanism eventual falls short and the RV progresses to failure and patient death. The specific aims of our investigations are to assess the effects of PAH therapies on RV in normal and hypertrophied states, as seen in PAH. We utilize human RV samples attained from cardiac surgical procedures to perform in-vitro analysis of protein and mRNA expression of the targets of PAH therapies. We also use a rat model of PAH and subsequent RV hypertrophy to verify human data and to also perform applied physiology experiments to isolate ex-vivo effects of PAH therapies on the RV. The experiments and data gathered in this thesis represent the insight into the importance of the RV in PAH therapies and how these therapies directly mediate the state of inotropy of the RV. A conclusion of greater importance is the better understanding of RV-specific changes in gene expression when the RV undergoes hypertrophy. By demonstrating the up-regulation of protein expression in RVH we are able to potentially tailor therapies to only improve performance of the diseased RV, while sparing the LV if it is otherwise normal. This is a true shift in paradigm as all current cardiac therapeutics effect both right and left ventricle. / Experimental Medicine

No description available.

The management and prevention of Sudden Cardiac Death remains a great challenge in modern Cardiology. Implantable Cardioverter Defibrillators (ICDs) have been shown to reduce mortality. Despite decades of research, the mechanisms are not fully understood and ICD treatment is crude, palliative and expensive. Nonetheless, outcome studies have helped to inform national and international guidance in the implantation of these devices. Patient selection is crucial to ensure correct patients are identified and appropriately treated. More refined and stringent risk stratification is needed to identify patients at high risk. This thesis examines non-invasive, readily measureable markers to see whether they can be used to assess the risk of ventricular arrhythmia in patients with cardiomyopathy who have indications for ICD implantation. Baseline data in the form of 12 lead electrocardiograms, echocardiography, 24 hour Holter monitoring and venous blood were obtained to analyse QT dispersion, Heart Rate Variability (HRV), QT Variability Index (QTVI), ECG restitution measures and NTproBNP levels in these patients. Patients were followed up for a two year period through the ICD clinic and appropriate therapy was recorded as a surrogate marker for ventricular arrhythmia. Patients with and without appropriate therapy were then compared to look for significant differences in the examined markers. The percentage of beats with a QT/TQ ratio>1 was associated with appropriate shocks when compared with no therapy (p=0.04). However, the result was not significant when all appropriate ICD therapy was compared with no therapy (p=0.06). This possibly reflects the period of time the heart spends on the more ‘unstable portion’ of the restitution slope in patients at highest risk. Median BNP was non-significantly higher in patients with arrhythmia compared to those who were shock free. None of the other examined markers were predictive of appropriate therapy. There is thus promise in the use of some non-invasive markers in the refinement of patient selection with LVSD being considered for ICD therapy.

The Romano-Ward syndrome is a familial disorder inherited as an autosomal dominant trait, the gene of which has been linked to the HLA locus on chromosome 6 or the Harvey-ras oncogene on chromosome 11. The genetic linkage, left and right ventricular function, and the integrity of the baroreflex were studied in subjects from two unrelated families with this condition. Neither family showed genetic linkage to either the HLA locus or to the Harvey-ras gene. Blood pool tomography was used to assess left and right ventricular function: left ventricular wall motion abnormalities were seen only in one family; the degree of dysfunction was related to the presence of symptoms. Minor disturbances of right ventricular function were seen in some subjects from both families, but did not correlate to the presence nor to the severity of symptoms. Using 14 frequencies of cyclical neck suction, the frequency response of the carotid baroreceptor heart-rate reflex was studied. One family had essentially a normal baroreflex. However, all members of the other family had similarly abnormal responses: a higher sensitivity at high and low suction frequencies, suggesting abnormalities of parasympathetic and sympathetic tone respectively. The Romano-Ward syndrome is a heterogeneous disorder: differences in genetic linkage (compared with historical controls), left ventricular function, and baroreflex sensitivity have been demonstrated.

Diss. (sammanfattning) Uppsala : Univ., 2001. / Härtill 5 uppsatser.

Thesis (Ph.D.)--University of Melbourne, Dept. of Medicine, The Royal Melbourne Hospital, 2010. / Typescript. Includes bibliographical references (leaves 164-202)

Thesis (Ph.D.)--Boston University