Diabetes Mellitus (DM) and insulin resistant (IR) are highly prevalent among heart failure (HF) patients. There is now increasing evidence to suggest a bidirectional relationship between IR and HF. DM and IR not only lead to heart failure, but heart failure can also lead to the development of DM or IR. The degree of IR also correlates with the severity and mortality of CHF. The pathophysiology of IR in CHF has yet to be fully defined. Activation of sympathetic nervous system, abnormal regulation of adipocytokines systems, activation of inflammatory and coagulation cascade, accumulation of glycated products, endothelial dysfunction and hyperinsulinaemia are potential explanations of the development of IR in CHF. Additionally, it remains to be determined if IR is merely a marker reflecting the severity of CHF or whether it contributes to the disease in CHF. If IR is truly a culprit that worsens CHF, reversing IR may potentially be a new target for treatment in CHF, which may result in an improvement in symptoms and even mortality in patients with CHF. However, there are concerns over the use of certain insulin sensitizers, most notably, the thiazolidinediones (TZDs), which has been linked with increased risk of hospitalizations for CHF and concerns regarding its association with increased myocardial infarction. Despite previous concerns of lactic acidosis, there is now evidence that metformin may not only be safe but could potentially be useful in the setting of CHF. We have conducted a randomised double-blind, placebo-controlled trial testing the hypothesis of reversing IR with metformin in insulin-resistant CHF will have beneficial effects. If IR is a possible target for the treatment of CHF, what are the new and potential treatment modalities? We have now had better understandings of the adipocytokines systems, which may prove to be a therapeutic option to improve IR in CHF. AMP-activated protein kinase (AMPK) pathway has become the focus of research as a novel therapeutic target in cardio-metabolic disease. It has been shown to mediate, at least in part, the effects of a number of physiological and pharmacological factors that improve IR. It also exerts beneficial effects on the vasculature and the heart. There have been some new AMPK activators that are currently being tested in vivo setting or phase 1-2 trials, and the early results are somewhat promising. Increased understandings and refreshed insights of IR and CHF have opened a new horizon and encouraged us to explore more therapeutics options in CHF.

Approximately 25% of those hospitalized with congestive heart failure are readmitted within 30 days after discharge. Because researchers and policy makers consider hospital readmission within 30 days for patients with heart failure to be a quality of care issue, the Centers for Medicare and Medicaid Services has imposed financial penalties of up to 3% of a hospital's Medicare revenue for 1 year for excessive readmissions, potentially impacting the financial sustainability of some organizations. The purpose of the study was to address the research gap regarding the outcome quality measure of hospital admissions from the emergency department (ED) and 2 each process and structure variables. The Donabedian conceptual framework was used to assess quality of care through the triad of structure, process, and outcome. The quantitative study comprised analysis of cross-sectional archival data from the 2015 National Hospital Ambulatory Care Survey using cross-tabulations with chi-square followed by multiple logistic regression analysis. Findings showed that process quality measures of being seen in the ED within 72 hours and total laboratory tests obtained in the ED were predictive of lower likelihood of admission. The structure quality measure of insurance was not predictive; however, being seen by provider type consulting physician was predictive of higher likelihood of admission, whereas being seen by a nurse practitioner was predictive of lower likelihood of hospital admission. The implications of this study for social change are helping hospitals maintain financial stability through avoidance of financial penalties for heart failure readmission, supporting access to care for patients by avoiding hospital closures.

Heart failure (HF) has a global significance for the older population and is the most common reason for hospitalization. Patients with HF can reduce their risk for hospital readmissions and adverse outcomes through self-management of their disease. Nurses are responsible for educating patients about HF self-management; however, nurses at the project site lacked sufficient understanding and confidence to perform adequate HF patient education, creating a gap in practice. This project was guided by Pender's health promotion model and adult learning theory with the goal to increase nurses' knowledge and confidence with the self-management principles of HF. The purpose of this project was to develop an educational program for nurses to increase their knowledge of HF disease management and patient self-management principles. The education program was supported by research literature and recommendations from the Agency for Healthcare Research and Quality, in addition to input from a planning team consisting of 3 nursing leaders from the project site. The planning team provided process evaluation regarding satisfaction with the planning process by completing an anonymous, 10-question, Likert-type survey. Seven project evaluations were completed and all respondents indicated that they agreed or strongly agreed in response to questions regarding the effectiveness of the project, it's planning, and the leader. At the completion of the project, the education program was delivered to the project site, with a plan for later implementation and learner evaluation using assessment tools of HF knowledge and confidence. This project has the potential to achieve positive social change in relation to nurses' commitment to improving patient outcomes through quality initiatives and dedication to the implementation of evidence-based practice, thus, promoting positive patient outcomes.

Heart failure (HF) is an escalating chronic disorder that impacts patients, families, and society. HF necessitates efficient transition of care and complex self-care knowledge in a population often burdened with low health literacy and high readmission rates. The purpose of this project was to improve transition of discharged HF patients from a Level 1 trauma system in a mostly rural area of South Carolina to its affiliated nurse-led HF clinic. The no-show rate for initial visits to the health care system's outpatient HF clinic by postdischarge patients was 59%. Using Henderson's need theory and Stevens's knowledge transformation model for theoretical guidance, a quality improvement project was conducted to identify factors related to no-show behavior in initial HF clinic visits using a retrospective chart audit of the first 50 no-show patients in a 90-day period. Data were collected from the electronic medical record and analyzed through descriptive statistics. Frequently noted factors were lack of literacy screening, use of assistive devices, and access issues related to distance to travel and transportation to the HF clinic. Recommendations included mandatory literacy level screening on admission, integration of an evidence-based health literacy screening tool into the electronic record, use of satellite HF clinic services, and consideration of a mobile HF clinic on wheels to better serve the rural population. Social change is expected to occur in this vulnerable population through these efforts to address health literacy issues and increase access to clinic care after hospital discharge.

Reversible protein phosphorylation is an essential component of metazoan signaling and cardiovascular physiology. Protein kinase activity is required for regulation of cardiac ion channel and membrane receptor function, metabolism, and transcription, and aberrant kinase function is widely observed across disparate cardiac pathologies. In fact, multiple generations of cardiac therapies (eg. beta-adrenergic receptor blockers) have targeted cardiac kinase regulatory cascades. In contrast, essentially nothing is known regarding the mechanisms that regulate cardiac phosphatase activity at baseline or in cardiovascular disease. Protein phosphatase 2A (PP2A) is a key phosphatase with multiple roles in cardiac physiology. Here we demonstrate the surprisingly complex regulatory platforms that control PP2A holoenzyme activity in heart. We present the first full characterization of the expression and regulation of the PP2A family of polypeptides in heart. We identify the expression of seventeen different PP2A genes in human heart and define their differential expression and distribution across species and in different cardiac chambers. We show unique subcellular distributions of PP2A regulatory subunits in myocytes, strongly implicating the regulatory subunit in conferring PP2A target specificity in vivo. We report striking differential regulation of PP2A scaffolding, regulatory, and catalytic subunit expression in multiple models of cardiovascular disease as well as in human heart failure samples. Importantly, we demonstrate that PP2A regulation in disease extends far beyond expression and subcellular location, by identifying and describing differential post-translational modifications of the PP2A holoenzyme in human heart failure. Furthermore, we go to characterize a mechanism for this method of post-translational modification that may represent a pathway capable of being therapeutically manipulated in human heart failure. Lastly we provide evidence that dysregulation of phosphatase activity contributes to the cellular pathology associated with a previously described inheritable human arrhythmia syndrome, highlighting the importance of the PP2A in cardiovascular physiology and disease. Together, our findings provide new insight into the functional complexity of PP2A expression, activity, and regulation in heart and in human cardiovascular disease and identify potentially new and specific gene and subcellular targets for the treatment of human arrhythmia and heart failure.

Abstract not available

Reversible protein phosphorylation is an essential component of metazoan signaling and cardiovascular physiology. Protein kinase activity is required for regulation of cardiac ion channel and membrane receptor function, metabolism, and transcription, and aberrant kinase function is widely observed across disparate cardiac pathologies. In fact, multiple generations of cardiac therapies (eg. beta-adrenergic receptor blockers) have targeted cardiac kinase regulatory cascades. In contrast, essentially nothing is known regarding the mechanisms that regulate cardiac phosphatase activity at baseline or in cardiovascular disease. Protein phosphatase 2A (PP2A) is a key phosphatase with multiple roles in cardiac physiology. Here we demonstrate the surprisingly complex regulatory platforms that control PP2A holoenzyme activity in heart. We present the first full characterization of the expression and regulation of the PP2A family of polypeptides in heart. We identify the expression of seventeen different PP2A genes in human heart and define their differential expression and distribution across species and in different cardiac chambers. We show unique subcellular distributions of PP2A regulatory subunits in myocytes, strongly implicating the regulatory subunit in conferring PP2A target specificity in vivo. We report striking differential regulation of PP2A scaffolding, regulatory, and catalytic subunit expression in multiple models of cardiovascular disease as well as in human heart failure samples. Importantly, we demonstrate that PP2A regulation in disease extends far beyond expression and subcellular location, by identifying and describing differential post-translational modifications of the PP2A holoenzyme in human heart failure. Furthermore, we go to characterize a mechanism for this method of post-translational modification that may represent a pathway capable of being therapeutically manipulated in human heart failure. Lastly we provide evidence that dysregulation of phosphatase activity contributes to the cellular pathology associated with a previously described inheritable human arrhythmia syndrome, highlighting the importance of the PP2A in cardiovascular physiology and disease. Together, our findings provide new insight into the functional complexity of PP2A expression, activity, and regulation in heart and in human cardiovascular disease and identify potentially new and specific gene and subcellular targets for the treatment of human arrhythmia and heart failure.

Heart failure is a chronic condition that increases the risk for death and disability. Beta blockers and ACE inhibitors have become standard treatments in heart failure because clinical trials have demonstrated their beneficial effect on mortality and morbidity in these patients. As not much is known about adherence to these medications, the main objectives of this project were to determine long term adherence to ACE inhibitors and beta blockers and determine how various degrees of adherence to a beta blocker can affect major health outcomes in patients with heart failure.<p> Data was obtained from Saskatchewan health from January 1, 1994 to December 31, 2003 for all heart failure patients from their first hospitalization for heart failure. Adherence was calculated using the fill frequency measure of adherence, and all survival analyses were completed using the Cox proportional hazards model.<p>Although 14, 000 patients were admitted to hospital for a first admission for heart failure, only 1143 subjects started a beta blocker and 5084 subjects started an ACE inhibitor within 3 months of the index hospitalization. Within the first year, adherence was excellent for both beta blockers (80.8 percent) and ACE inhibitors (82.5 percent). The proportion of patients remaining adherent slowly decreased to reach approximately 60 percent, for both medication classes, after 4 years. There was no significant difference in all-cause mortality between patients with high adherence and low adherence, but there appeared to be a trend towards decreased survival time in those remaining adherent throughout the study period [HR = 1.18 (95% CI: 0.98 to 1.43; p=0.07)].<p>Since the overall rate of adherence to beta blockers was excellent in most patients during the first year, it is possible that non-adherence is not responsible for a significant burden of mortality in Saskatchewan heart failure patients, and perhaps and the focus of quality improvement should be optimal prescribing of evidence-based therapies, and continued adherence over time.

The tumour suppressor p27kip1 (p27) is a potent inhibitor of cell growth and proliferation. We identified NF-κB activator, IKKα, as a novel interacting partner of p27 in a protein microarray screen. Both the IKKα and IKKβ components of the IKK complex were mapped to the C-terminal domain of p27. To investigate the physiological function of the p27-IKK interaction, we employed a well-established model of LPS-induced sepsis which is known to activate the IKK/NF-κB pathway. Lentivirally-mediated overexpression of p27 blocked LPS activation of NF-κB. Furthermore, in LPS-injected animals transduced with TAT-p27, a significant improvement in the left ventricular function of the heart was observed. TAT-p27 treatment was also shown to attenuate the endotoxin effect and significantly improve survival compared to both saline and TAT-LacZ controls. Our results indicate that p27 attenuates inflammation, possibly through inhibiting the IKK-dependent activation of NF-κB, thus supporting a novel link between both cell cycle regulation and inflammation.

Sodium restriction is the primary dietary therapy for individuals with heart failure (HF); however, there is little information available to support or refute the use of sodium restriction to manage HF. The overall goal of this work was to generate data related to dietary sodium in patients with chronic HF that would contribute to the development of evidence-based guidelines. The specific objectives were to investigate the optimal methods for measuring sodium intake in HF, to describe the habitual consumption of sodium and other nutrients in HF, and to evaluate the relationship between sodium intake and clinical outcomes in HF. We studied stable ambulatory HF patients who were optimally medicated and participating in multidisciplinary HF programs. We determined that: (1) a strong relationship exists between 24-hour urine collections and food records for sodium intake assessment in non-HF cardiac patients and HF patients not taking loop diuretics. However, the relationship between urinary sodium excretion and sodium intake in HF patients taking loop diuretics was disturbed, suggesting that food records may be a better method for estimating sodium intake in this group. (2) Mean sodium intake in HF and non-HF cardiac patients was similar, and approximately half of patients in each group had sodium intake levels that exceeded the Dietary Reference Intakes tolerable upper level of 2300 mg/d. We also found that both groups had inadequate intakes of several nutrients, including potassium, calcium, magnesium, folate, and vitamin D and E. (3) Finally, we showed that a high sodium diet (>2800 mg/day) in HF was associated with risk of acute decompensated HF, all-cause hospitalization, and all-cause mortality over a median 3 year follow-up period. This is the first published study that prospectively related sodium intake to clinical outcomes in HF. In summary, these data provide novel contributions related to the measurement of sodium intake that can be used in clinical or academic settings. We also describe inadequacies in intake of several vitamins and minerals, which could be addressed through dietary counselling. Finally, we importantly offer insight into a threshold of sodium intake (>2800 mg/day) that could contribute to adverse clinical outcomes in HF.