京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19572号 / 医博第4079号 / 新制||医||1013(附属図書館) / 32608 / 京都大学大学院医学研究科医学専攻 / (主査)教授 萩原 正敏, 教授 小西 靖彦, 教授 齊藤 博英 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19601号 / 医博第4108号 / 新制||医||1014(附属図書館) / 32637 / 京都大学大学院医学研究科医学専攻 / (主査)教授 岩井 一宏, 教授 柳田 素子, 教授 山下 潤 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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No description available.

ABSTRACT Chronic activation of the sympathetic nervous system, via β-adrenoreceptor (AR) stimulation, contributes toward progressive heart failure. However, in this regard there are some outstanding issues which require clarity. First, in addition to contributing toward progressive heart failure, it is not clear whether chronic β-AR activation can also initiate cardiac decompensation. If so, the mechanisms of this effect also need to be determined. Second, the role of functional variants of β-AR genes as determinants of either the development or progression of heart failure requires elucidation. Moreover, whether there is any practical value in genotyping of patients for these variants has yet to be determined. These questions were addressed in the present thesis. With respect to the question of whether chronic β-AR activation initiates cardiac decompensation, the mechanisms responsible for the transition from compensated cardiac hypertrophy to heart failure in pressure overload states, such as hypertension, are uncertain. In this thesis I explored whether chronic sympathetic nervous system activation, produced by daily administration of a β-AR agonist, could promote the transition to cardiac pump failure in spontaneously hypertensive rats (SHR) with compensated cardiac hypertrophy. After 5 months of daily administration of a β-AR agonist, SHR developed marked left ventricular pump dysfunction, whereas normotensive control rats maintained pump function. The pump dysfunction noted in SHR was attributed to marked chamber dilatation with wall thinning, whilst myocardial contractile function appeared to be intact. The changes in cardiac structure and function noted after chronic β-AR activation in SHR were similar to those noted in SHR with advanced heart failure. These data provided the first evidence to indicate that chronic β- AR activation can promote the transition to decompensated cardiac hypertrophy in pressure overload states, and that this effect is principally mediated by adverse structural remodeling of the cardiac chamber. iii The mechanisms responsible for the effect of chronic β-AR activation on cardiac chamber dilatation were subsequently studied. The identified mechanisms included activation of an enzyme that degrades myocardial collagen (matrix metalloproteinase 2) and an increase of myocardial collagen of the type that is susceptible to collagen degradation (non-cross-linked collagen). I also excluded alternative potential mechanisms such as necrosis, apoptosis and an accumulation of type III collagen. However, previous studies have indicated that increases in myocardial collagen concentrations determine myocardial stiffness and not cardiac chamber dilatation. Hence, I performed a study to examine whether the impact of increases in myocardial collagen concentrations on cardiac structure and function depends on the qualitative changes in myocardial collagen. Indeed, using a variety of models of pressure overload hypertrophy associated with increases in myocardial collagen concentrations, I was able to provide evidence to support the theory that increases in myocardial collagen of the cross-linked phenotype will promote myocardial stiffness, whereas increase in myocardial collagen of the non-cross-linked phenotype promotes cardiac dilatation. With respect to the question of whether functional variants of β-AR genes contribute toward either the development or progression of heart failure, I studied the role of both functional β1-AR and β2-AR (together with a α2C-AR) gene variants in black South Africans with idiopathic dilated cardiomyopathy (IDC). In a prospective study I obtained data to indicate that the relationship between functional β2-AR genotypes and the progression to hospitalization, death or transplantation; a reduced exercise capacity, and left ventricular functional responses to b-blocker therapy, as described by other groups, is unlikely to be attributed to an independent effect of genotype on cardiac chamber dimensions and pump function. Moreover, I was able to show that contrary to what had previously been suggested, genotyping black subjects for functional α2C-AR iv and β1-AR gene variants is of little use when predicting the development or severity of IDC in this population group.

Rate of readmission among hospitalized heart failure (HF) patients is used as an indicator of quality and efficiency of healthcare. A low sodium diet is a component of the accepted treatment for HF. Instruction by dietitians may help reduce dietary sodium without negatively affecting quality of life. The effect of low sodium diet education on hospital readmission within 30 and 45 days of discharge for HF patients (N=52) was conducted. Chi-square analysis determined education did not significantly affect remittance within 30 (P=.143) or 45 days (P=.474). Patients readmitted within 30 days were older (P=.005). Men were more likely to be readmitted than women within 30 (P=.021) and 45 days (P=.019). Higher NT-proBNP levels were observed in individuals readmitted within 30 (P=.011) and 45 days (P=.010). Low sodium diet education did not affect readmission but older age, male sex, and higher NT-proBNP values increased the rate of readmission.

Patient-reported outcomes (PROs) produce meaningful information about patient-perceived health status reported directly by patients. Routine collection of PROs data is particularly important in chronic conditions, such as heart failure (HF). Major cardiovascular societies and regulatory agencies encouraged PRO inclusion in randomized controlled trials (RCTs), but PROs remain underutilized as a key outcome in these studies. In this systematic review, we aimed to evaluate temporal trends and explore trial characteristics associated with PRO inclusion in HF RCTs published in high-impact medical journals. We also assessed the quality of PRO reporting against the Consolidated Standards of Reporting Trials PRO extension. We found that over half of HF RCTs included a PRO. The proportion of RCTs with PROs increased significantly since 2000. A number of RCT characteristics such as multicentre; medium-sized (n = 51-250 participants); trials coordinated in Central and South America; and that tested health services, devices or surgery, exercise and rehabilitation interventions were independently associated with higher odds of PRO inclusion. The quality of PRO reporting was modest, with better reporting in RCTs with PROs a primary or co-primary endpoint. Consistent PRO inclusion and high-quality reporting are necessary to increase the utility of these findings by patients, clinicians, and health care policy makers. / Thesis / Master of Science (MSc)

A Case Report of Catastrophic Antiphospholipid Syndrome with Libman-Sacks Presenting as Interstitial Pneumonia Chassidy Sumler Martin, MS, Rocco Cannistraro, MD Antiphospholipid syndrome (APS) is an autoimmune condition characterized by vascular thromboses and a positive antiphospholipid antibody. Catastrophic antiphospholipid syndrome (CAPS) is a rare disease that often results in death. CAPS is the most severe form of APS, which can develop in a short period of time and occurs in less than 1% of people with APS. CAPS involves multiple organs simultaneously with diffuse microvascular and macrovascular involvement. Here, we present a case of catastrophic antiphospholipid syndrome presenting as interstitial pneumonia that rapidly progressed to acute renal failure, acute ischemic cerebral infarcts, cardiac valvular vegetations, and heart failure. This case report aims to bring awareness of prompt medical suspicion and treatment of CAPS in hopes of improving disease outcomes.

The purpose of this study was to describe the experiences of rural community-dwelling older adults with heart failure who required assistance with activities of daily living (ADLs) and instrumental ADLs (IADLs). The context of the study was a rural area in a southern U.S. state. Twenty older adults with ADL/IADL needs living in the rural area were recruited during hospitalization and interviewed in their homes after discharge. The semi-structured interview focused on ADLs/IADLs and community resources. This qualitative descriptive study used hermeneutic methods for analysis. Four themes were identified: Accepting Limitations, Disappointments and Unmet Expectations, Figure It Out, and Complex Connections. The findings indicate that despite the older adults’ medical conditions, they were able to set up complex arrangements, which allowed them to remain in their homes. Understanding the help older adults require after discharge will assist nurses in developing programs that are available, accessible, and acceptable to older adults who live in rural areas.

No description available.