Pump thrombosis is the epitome of left ventricular assist device dysfunction for end-stage heart failure patients. With the increased utilization of implantable, long-term, left ventricular assist devices (LVADs), understanding the implications associated with device orientation and interaction with the body is exceedingly important. Components associated with pump thrombosis in the Thoratec© HeartMate II™ (HMII) and the HeartWare© HVAD® devices include the inflow cannula, the outflow graft, and the pump elements as well as pump pocket depth for the HMII specifically. Several studies have been conducted to analyze these interactions with the HMII, however there is minimal to no data available analyzing how the device orientation of the HeartWare HVAD affects hemodynamics and a patient’s risk for developing pump thrombosis. Therefore, the purpose of this pilot study is the simulate the hemodynamic implications associated with Sub-optimal cannula angulation of the HVAD. Using Solidworks 2016 Ed., a simplified, hemo-static model of the left side of the heart was created. Dimensions for the atria, ventricle, and mitral valve were determined through the combination of Trans-Esophageal Echo cardiogram data as well as literature references. Three different inflow cannula angle scenarios were developed including a Control, a Clinically Optimal, and a Sub-optimal. Assumptions included body temperature, no accumulation within the ventricle, and no ejection or contraction. The model consists of static continuous flow set to 5 liters per minute with the assumption that the HeartWare HVAD is completely supporting the left ventricle. The results include both qualitative and quantitative data. Flow trajectory plots for each cannula scenario depict the hemodynamic flow patterns for different time points. Results show visible changes in the Sub-optimal orientation when compared to both the Control and the Clinically Optimal scenario. Additionally, it was determined that there were no statistically significant differences in the velocity vectors for any of the scenarios however, the shear stress values were determined to be significantly different for all time points, p < 0.001 for all scenarios when compared to Control. Though there are several limitations of this study, with sub-optimal inflow cannula angulation, there is a potential increased risk of hemolysis due to increased shear stress.

Background: Aortic valve insufficiency (AI) at the time of left ventricular assist device (LVAD) insertion needs to be corrected, however there is little known about how to manage bioprosthetic valvular AI. Case presentation: A 55-year-old female with dilated cardiomyopathy who previously had a bioprosthetic aortic valve replacement needed a LVAD as a bridge to transplant. Her left ventricular ejection fraction was 10% and had mild to moderate transvalvular AI. She underwent a HeartWare HVAD insertion along with aortic valvular coaptation stitch repair (Park's stitch) to the bioprosthetic valve. Conclusion: Her AI improved to trivial with minimal ejection through the bioprosthetic valve. She was transplanted 6 months following the surgery. A Park's stitch to the bioprosthetic aortic valve with more than mild AI might be a good option for bridge to transplant patient.

In this study, the relationship between maximal aerobic capacity (VO₂max) and left ventricular function was examined in two distinct age groups. A young group (20 - 30 years of age) and an elderly group (over 60 years of age) were compared. Left ventricular function was examined over wide variations in preload accomplished by 5º head-down tilt (TILT) for ninety minutes and lower body negative pressure (LBNP) to -40 mm Hg. with two-dimensional echocardiography. A greater response to an increase in preload (TILT) was related to high VO₂max levels in the young subjects but not in the elderly groups of subjects, suggesting that lower VO₂max levels of the elderly population affected the mechanism of response to the increased levels of preload. Additionally, in the elderly, greater reductions in ventricular volume reflected increased peripheral pooling due to decreased venous tone and/or increased venous compliance during LBNP and were related to increased VO₂max. In the young, VO₂max does not appear to affect the response to reduced preload.

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

<p>QC 20170306</p>

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.

Heart failure is a progressive condition that affects over 5.7 million Americans and costs associated with heart failure account for 2-3 % of the national health care budget. The high rates of morbidity and mortality along with increased costs from readmissions associated with advanced heart failure have led to the exploration of advanced treatments such as left ventricular assist devices (LVADs). LVADS have demonstrated morbidity and mortality benefit but cost remains extensive with costs per quality-adjusted years > $400,000. With this in mind, it is important to identify those who are most likely to benefit from an LVAD to avoid unfavorable outcomes and cost. Although general guidelines and criteria for patient eligibility have been established, choosing patients for LVAD implantation remains challenging. A new focus on patient selection involves the presence of frailty. While frailty has been studied in the elderly population and in patients undergoing cardiac surgery, frailty in patients undergoing left ventricular assist device (LVAD) remains controversial. The purpose of this dissertation was to examine measures of frailty in patients undergoing LVAD implantation. The specific aims of this dissertation were to: (1) identify a feasible frailty measure in adults with end-stage heart failure who underwent LVAD implantation by testing the hypothesis that frailty would predict 30 day rehospitalization rates using Fried’s criteria, Short Physical Performance Battery test, handgrip strength, serum albumin and six minute walk test (2) Determine whether frailty measures improve 3 months post LVAD implantation (3) compare sensitivity of these three measures to change in frailty. Surgical approaches, including heart transplantation and LVAD implantation, for patients with end-stage heart failure was discussed in this dissertation. Data from two subsets of participants who underwent LVADS at the University of Kentucky between 2014 and 2017 were included in the analysis for this dissertation. In the first study, we found that none of the measures are good predictors of frailty in patients with advanced heart failure who undergo LVAD implantation. Handgrip was the only marker of frailty that predicted 30 day readmission but the relationship was a negative association. In the second study, six-minute walk and low serum albumin levels reflect short-term improvement in frailty. These simple measures may be used to determine those patients who are responsive to LVAD implantation. The findings of these studies filled some gaps in our understanding of markers of frailty in patients undergoing LVADs. We gained a better understanding of which markers of frailty are likely to improve in most people after LVAD implantation and thus frailty should not preclude candidate selection for an LVAD. Subsequently, more research is needed to investigate these markers and outcomes.

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>