Made available in DSpace on 2014-06-11T19:32:12Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-02-10Bitstream added on 2014-06-13T21:03:38Z : No. of bitstreams: 1 roscani_mg_dr_botfm.pdf: 1793815 bytes, checksum: ef58e271a6e22be8d19da25e6d3d13c8 (MD5) / A adaptação cardíaca à insuficiência aórtica resulta em hipertrofia excêntrica seguida de disfunção ventricular e insuficiência cardíaca. A evolução desse processo ainda não é bem compreendida. Avaliar a adaptação cardíaca à insuficiência aórtica aguda experimental por meio de ecocardiografia, identificar os marcadores anatâmicos de transição da hipertrofia excêntrica compensada para a fase descompensada e verificar se existe associação entre marcadores anatâmicos e de disfunção ventricular e fibrose miocárdica. Estudo experimental com 35 ratos Wistar machos, 23 animais submetidos à insuficiência aórtica aguda (grupo IAO) e 12 animais a procedimento simulado (Grupo Controle). Todos os animais foram seguidos com ecocardiogramas seriados com 1, 4, 8 e 16 semanas. No término do protocolo, foi realizada mortometria do tecido cardíaco. A análise estatística foi efetuada por meio do teste t de Student, Mann-Whitney, ANOVA de medidas repetidas, Modelo de Regressão Longitudinal (GEE) e Modelo de Regressão Linear simples e múltipla. Em todos os casos, o nível de significância adotado foi p<O,05. Houve interação entre tempo e insuficiência aórtica para aumentar o diâmetro diastólico do ventrículo esquerdo (DDVE, p<O,001), a área normalizada do átrio esquerdo (AAE(AAD, p==O,0011) e índice de esfericidade (I(L, p<O,001) e diminuir a do ventrículo esquerdo (pp (DDVE, p=O,009) e a porcentagem de encurtamento (%E, p<O,001). Comparativamente à semana 1, o aumento do l(L na semana 4 (0,72±O,10 vs. O,65±O,60; p<O,001) ocorreu anteriormente ao aumento do DDVE (9,OO±1,30 mm vs. 7,60±O,63 mm; p<O,05), observado na semana 8. Também precedeu o aumento da AAE(AAD (1,59±O,35 vs. 1,45±O,20; p<O,05) e a redução da PP(DDVE (O,18±O,04 vs. O,20±O,02; p=O,003), observados na semana 16. Houve interação entre tempo e I(L para reduzir a %E (p<O,001)... / To evaluate the cardiac adaptation to experimental acute aortic regurgitation by echocardiography, to identify the anatomical markers of the transition from compensated eccentric hypertrophy to decompensated stage and to investigate the association between anatomical markers of ventricular dysfunction and myocardial flbrosis. Thirty flve Male Wistar rats underwent surgical procedure for inducing acute aorta regurgitation (AR group, n= 23) or sham operation (SH group, n= 12). Transthoracic echocardiograms were performed at 1, 4, 8 and 16 weeks after procedure. At the end of the protocol, morphometry of the heart tissue was performed. Statistical analyses used t test, Mann-Whitney, repeated measures ANOVA, GEE model (General Estimative Equation, STATA 10.0), linear regression model and multiple linear regression. In ali cases, the levei of significance was p <0.05. There were interactions between time and AR for increasing left ventricle diastolic diameter (LVDD, p<0.0011), normalized left atrium area (LAA, p=0.0011) and sphericity index (SI, p<0.0011), and for decreasing relative wall thickness (RWT, p=0.002) and fractional shortening (F5, p<0.001). Compared to week 1, the increased SI at week 4 (0.72±0.10 vs. 0.65±0.60; p<0.001) preceded the LVDD enlargement (9.00±1.30mm vs. 7.60±0.63mm; p<0.05) and LAA increasing (1.59±0.35 vs. 1.45±0.20; p<0.05) observed at week 8 and RWT decreasing observed at week 16 (O.18±0.04 vs. 0.20±0.02; p=0.003). There was an interaction between time and SI for reducing F5 (p<0.001). LV systolic dysfunction was detected at week 8 and preceded LAA enlargement at week 16. This suggested increased LV diastolic pressure and it was coincident with the decreased RWT indicating LV dilation

Background: Heart failure is a clinical syndrome occurring from the heart’s inability to effectively fill and or pump blood, it is the most common reason for admission in elderly patients. Guideline directed medical therapy refers to implementation of all class I agents to reduce patient morbidity and mortality, unless there is an appropriate contraindication. Appropriate beta blocker (BB), angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB), and aldosterone antagonist (AA) are recommended to be prescribed together prior to discharge for a hospital admission for decompensated heart failure with reduced ejection fraction (HFrEF). Get With The Guidelines – Heart Failure (GWTG- HF) is an online quality improvement project that assists hospitals in providing guideline directed care. Objective: The purpose of this study was to determine if implementation of the GWTG-HF program, increases provider adherence to guideline directed medical therapy (GDMT) for patients admitted with a primary diagnosis of decompensated HFrEF at Banner University Medical Center Tucson (BUMCT). Design: This is a quality improvement project with a pre and post test descriptive design. Setting: BUMCT from 10/04/17 – 11/08/17 Participants: Fifty-five patients discharged with the primary diagnosis of decompensated HFrEF Measurements: Baseline guideline adherence for a 30-day period was compared to guideline adherence after the initiation of the GWTG-HF program. Results: The 24 patients pre intervention were compared to 31 patients post intervention. The following results were found when comparing pre and post adherence rates: BB adherence 92% versus 100%, ACEI/ARB adherence 100% versus 94%, AA adherence 67% versus 84%, and guideline directed medical therapy 58% versus 81%. There were no statistically significant differences for the pre and post adherence rates. Conclusion: Although, there were no statistically significant differences found to support that implementation of the GWTG-HF program, increases providers adherence to GDMT for patients admitted with a primary diagnosis of decompensated HFrEF, the trends were clear. In three out of four class I agents, there was an increase in appropriate provider prescribing per the guidelines.

Abstract Right heart failure may be caused by several etiologic factors such as pulmonary embolism, post coronary bypass, chronic obstructive pulmonary disease (COPD) and right heart infarction. Traditionally, treatment has consisted of fluid loading (volume expansion) and the use of inotropic agents. In the present series of studies, an experimental model of acute right heart failure was developed using right heart infarct. Treatment with drugs chosen to specifically improve right heart performance was then evaluated. The drugs used in this series were aminophlline, adenosine, nitric oxide (NO) and losartan. Aminophylline transiently improved cardiac index and pulmonary vascular resistance, but simultaneously caused an increase in heart rate and a decrease in stroke volume. Although it may reduce right heart afterload, aminophylline did not improve overall cardiac function in this experimental model of right heart infarction. Adenosine affected an increase in cardiac index during the adenosine infusion and in stroke index, while pulmonary vascular resistance and mean pulmonary pressure were decreased. There was a marked decrease in systemic vascular resistance as a result of the drug. Heart rate remained unchanged by the infusion. Discontinuation of the drug resulted in a rapid reversal of the hemodynamic changes. The continuous infusion of adenosine therefore appears to cause an effective arterial vasodilation, with a consequent unloading of right heart afterload. NO treatment significantly reduced right heart afterload. A significant deterioration was observed in cardiac output as well as in left and right ventricle stroke work indices. The use of NO in this model of right heart infarct affected a decrease in both right heart afterload and left heart preload, with an overall deterioration in global hemodynamics. Losartan was shown to decrease central venous pressure and wedge pressure, while cardiac output, left ventricle stroke work and stroke volume all showed improvement. Compared to the control animals, pulmonary vascular resistance, systemic vascular resistance and systemic pressures were unaffected by the drug, as was heart rate. An inhibition of angiotensin II action may therefore be of benefit in the treatment of right heart failure symptoms during the first hours after right heart infarct.

Background: Cardiac resynchronisation therapy (CRT) is a pacemaker-based therapy for patients with heart failure and dyssynchrony manifest as prolonged QRS duration. Approximately 30% fail to respond either symptomatically or echocardiographically. The role of several echocardiographic parameters to select patients and improve response rate has been studied. The utility of these parameters remains unclear. In particular recent advances in echocardiography with speckle tracking technology may provide more accurate assessment of dyssynchrony. This study aims to explore the role of echocardiography in prediction of CRT response and investigate mechanisms involved in response.Methods:Patients undergoing CRT according to national guidance were recruited. Baseline assessment included clinical examination, quality of life questionnaire, six minute walk test, electrocardiogram and detailed echocardiography. Follow-up assessment was performed six months after CRT. Response was defined as ≥15% reduction in left ventricular end-systolic volume. Baseline parameters of echocardiographic dyssynchrony were compared between responders and non-responders. Individual baseline and follow-up echocardiograms also were examined to assess mechanism of response.Results:51 patients were recruited and 40 patients completed six months follow-up. Echocardiographic response rate was 67.5%. Baseline parameters of dyssynchrony were not significantly different between responders and non-responders, and receiver operating characteristic (ROC) curve analysis suggested echocardiographic parameters have no role in prediction of response beyond QRS duration. Study of individual echocardiograms demonstrated several mechanisms of CRT response the relative importance of which vary between patients.Conclusion:Single echocardiographic dyssynchrony parameters appear to have no role in the prediction of CRT response. However, several mechanisms of response to CRT are identified, each of which may be identified echocardiographically, and echocardiography therefore continues to have an important role in pre-assessment of patients undergoing CRT.

Heart failure is responsible for one in twenty deaths in the UK, and as the average age of the general population increases that number is predicted to rise over the coming years. Hypertrophic growth is believed to be an adaptive response to a chronic increase in workload under circumstances such as hypertension, yet it is also known to contribute to the pathological progression into heart failure. Abnormal calcium handling is known to play a critical role in determining disease progression, not only through its function as the driving force behind myocardial contraction and relaxation but also through directing the signals which regulate hypertrophic growth. Both isoforms 1 and 4 of the diastolic calcium extrusion pump plasma membrane calcium ATPase (PMCA) are present in the heart, yet unlike in other cell types their contribution to overall calcium clearance is only small; however their role in the disease process is yet to be defined. A novel mouse line was generated in which both PMCA1 and 4 were deleted from the myocardium (PMCA1:4dcko mice). Through comparison with PMCA1 knockout mice (PMCA1cko) this thesis set out to identify the specific function of each pump under normal conditions and during the development of pathological hypertrophy induced by pressure overload through transverse aortic constriction (TAC).Under basal conditions each isoform functioned independently, PMCA1 to extrude calcium during diastole and PMCA4 to regulate calcium levels during systole; however the loss of neither isoform impacted significantly on cardiac function. In response to TAC, PMCA1cko mice progressed rapidly into decompensation and displayed signs of systolic failure after just 2 weeks, whilst cardiac function was preserved in TAC controls. Calcium handling analysis revealed that prior to the onset of failure PMCA1cko mice displayed a distinct lack of adaptive changes to calcium cycling which were present in controls. In stark contrast, the additional loss of PMCA4 led to an attenuated hypertrophic response to TAC in PMCA1:4dcko mice which remarkably preserved cardiac function despite the absence of PMCA1. This adds to accumulating evidence which suggests that the inhibition of PMCA4 may be protective during the development of pathological hypertrophy, whilst highlighting the possibility for a novel role for PMCA1 in coordinating essential adaptations required to enhance calcium cycling in response to the increased demands imposed on the left ventricle during pressure overload.

Cardiovascular disease (CVD) is the leading cause of death worldwide and is expected to increase in prevalence. As a result of the individual and systemic healthcare impacts of CVD, heart failure, and its subsets, focusing on the alleviation of cardiac dysfunction and restoration of autonomic imbalance is paramount. Most research regarding cardiovascular disease is focused on mitigating heart failure from a cardiovascular perspective. However, this review will investigate heart failure from a neuroscientific perspective, highlighting the influence of the renin-angiotensin-aldosterone system, autonomic imbalance, and neuroinflammation on the progression of heart failure. By doing so, this research will bring light to how neuroscience may be applied to the cardiovascular system, and how interventions, such as vagal nerve stimulation, may be an untapped resource in mitigating the progression of heart failure. This review examined current relevant research to understand the brain regions implicated in the progression of heart failure, and to better understand how the nervous system may be modulated to improve heart failure outcomes through vagal nerve stimulation. This review sets the conceptual framework for future research to examine the structural changes observed in research animals who receive vagal nerve stimulation.

Background - Heart failure costs Americans billions of dollars a year and takes a toll on the patients afflicted by the disease. Recent changes in how healthcare systems and providers are reimbursed have motivated them to find new ways to prevent heart failure readmission. There is no cure for heart failure so healthcare providers try to help patients manage their symptoms. Physical activity is one of the interventions healthcare providers recommend for their patients in the management of heart failure. The Physical Activity Vital Sign is a tool that can be quickly administer and has significant validity. Objective - The purpose of our research is to determine if physical activity, as measured by the Physical Activity Vital Sign, influences 30-day heart failure readmissions. Methods - A retrospective chart review was used to evaluate patients' charts that had a heart failure admission between January 1, 2016 and August 31, 2018. We used multiple regression to analyze how the Physical Activity Vital Sign predicts 30-day heart failure readmission rates, while controlling for age, sex, race, ejection fraction, body mass index, length of hospital stay, brain natriuretic peptide, and compliance with the heart failure core measures. Results - Data was analyzed from 270 heart failure admissions in the study period. The average duration of moderate intensity PA was 20.9 minutes per week; just less than three minutes per day on average. A Pearson Correlation matrix illustrated significant relationships between some of the independent variables. Multiple linear regression demonstrated p=0.376, which was statistically insignificant. Conclusions - The study did not find a significant relationship between physical activity, as measured by the Physical Activity Vital Sign, and heart failure readmissions but physical activity remains important in managing heart failure.

Background The role of statins in patients with heart failure (HF) of different levels of left ventricular ejection fraction (LVEF) remains unclear especially in the light of the absence of prospective data from randomized controlled trials (RCTs) in non-ischemic HF, and taking into account potential statins’ prosarcopenic effects. We assessed the association of statin use with clinical outcomes in patients with HF. Methods We searched PubMed, EMBASE, Scopus, Google Scholar and Cochrane Central until August 2018 for RCTs and prospective cohorts comparing clinical outcomes with statin vs non-statin use in patients with HF at different LVEF levels. We followed the guidelines of the 2009 PRISMA statement for reporting and applied independent extraction by multiple observers. Meta-analyses of hazard ratios (HRs) of effects of statins on clinical outcomes used generic inverse variance method and random model effects. Clinical outcomes were all-cause mortality, cardiovascular (CV) mortality and CV hospitalization. Results Finally we included 17 studies (n = 88,100; 2 RCTs and 15 cohorts) comparing statin vs non-statin users (mean follow-up 36 months). Compared with non-statin use, statin use was associated with lower risk of all-cause mortality (HR 0.77, 95% confidence interval [CI], 0.72–0.83, P < 0.0001, I2 = 63%), CV mortality (HR 0.82, 95% CI: 0.76–0.88, P < 0.0001, I2 = 63%), and CV hospitalization (HR 0.78, 95% CI: 0.69–0.89, P = 0.0003, I2 = 36%). All-cause mortality was reduced on statin therapy in HF with both EF < 40% and ≥ 40% (HR: 0.77, 95% Cl: 0.68–0.86, P < 0.00001, and HR 0.75, 95% CI: 0.69–0.82, P < 0.00001, respectively). Similarly, CV mortality (HR 0.86, 95% CI: 0.79–0.93, P = 0.0003, and HR 0.83, 95% CI: 0.77–0.90, P < 0.00001, respectively), and CV hospitalizations (HR 0.80 95% CI: 0.64–0.99, P = 0.04 and HR 0.76 95% CI: 0.61–0.93, P = 0.009, respectively) were reduced in these EF subgroups. Significant effects on all clinical outcomes were also found in cohort studies’ analyses; the effect was also larger and significant for lipophilic than hydrophilic statins. Conclusions In conclusion, statins may have a beneficial effect on CV outcomes irrespective of HF etiology and LVEF level. Lipophilic statins seem to be much more favorable for patients with heart failure. / Revisión por pares

Osteopontin (OPN) plays an important role in left ventricular (LV) remodeling after myocardial infarction (MI) by promoting collagen synthesis and accumulation. This study tested the hypothesis that MMP inhibition modulates post-MI LV remodeling in mice lacking OPN. Wild-type (WT) and OPN knockout (KO) mice were treated daily with MMP inhibitor (PD166793, 30 mg/kg/day) starting 3 days post-MI. LV functional and structural remodeling was measured 14 days post-MI. Infarct size was similar in WT and KO groups with or without MMP inhibition. M-mode echocardiography showed greater increase in LV end-diastolic (LVEDD) and end-systolic diameters (LVESD) and decrease in percent fractional shortening (%FS) and ejection fraction in KO-MI versus WT-MI. MMP inhibition decreased LVEDD and LVESD, and increased %FS in both groups. Interestingly, the effect was more pronounced in KO-MI group versus WT-MI (P < 0.01). MMP inhibition significantly decreased post-MI LV dilation in KO-MI group as measured by Langendorff-perfusion analysis. MMP inhibition improved LV developed pressures in both MI groups. However, the improvement was significantly higher in KO-MI group versus WT-MI (P < 0.05). MMP inhibition increased heart weight-to-body weight ratio, myocyte cross-sectional area, fibrosis and septal wall thickness only in KO-MI. Percent apoptotic myocytes in the non-infarct area was not different between the treatment groups. Expression and activity of MMP-2 and MMP-9 in the non-infarct area was higher in KO-MI group 3 days post-MI. MMP inhibition reduced MMP-2 activity in KO-MI with no effect on the expression of TIMP-2 and TIMP-4 14 days post-MI. Thus, activation of MMPs contributes to reduced fibrosis and LV dysfunction in mice lacking OPN.

The heart failure illness trajectory is both complex and unpredictable, which makes providing palliative care services to patients with heart failure a challenge. As a result, although services are needed, few tend to be offered beyond basic medical management. The traditional model of palliative care is typically based on palliative care being considered a system of care delivery most appropriate for patients with a predictable illness/death trajectory, such as terminal cancer. This type of model, which is based on the ability to predict the course of a terminal disease, does not fit the heart failure trajectory. In this article, we propose a new model of palliative care that conceptualizes palliative care as a philosophy of care that encompasses the unpredictable nature of heart failure.