SHF
domain-containing adapter protein F
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To assess the clinical utility of the Gold Standards Framework Prognostic Indicator Guide (GSF) and the Seattle Heart Failure Model (SHF) to identify patients with chronic heart failure (CHF) in the last year of life. An observational cohort study of 138 community based ambulatory patients with New York Heart Association (NYHA) class III and IV CHF managed by a specialist heart failure nursing team. 12 month mortality, and sensitivity and specificity of GSF and SHF. 138 CHF patients with NYHA class III and IV symptoms were identified from a population of 368 ambulatory CHF patients. 119 (86%) met GSF criteria for end of life care. The SHF model identified six (4.3%) patients with a predicted life expectancy of 1 year or less. At the 12 month follow-up, 43 (31%) patients had died. The sensitivity and specificity for GSF and SHF in predicting death were 83% and 22%, and 12% and 99%, respectively. Receiver operator characteristic analysis of SHF revealed a C index of 0.68±0.05 (95% CI 0.58 to 0.77). Chronic kidney disease (serum creatinine ≥140 μmol/l) was a strong univariate predictor of 12 month mortality, with a sensitivity of 56% and specificity of 72%. Neither the GSF nor the SHF accurately predicted which patients were in the last year of life. The poor prognostic ability of these models highlights one of the barriers to providing timely palliative care in CHF.
MeSH Terms
- Age Factors
- Aged
- Female
- Follow-Up Studies
- Heart Failure
- Humans
- Incidence
- Life Expectancy
- Male
- Population Surveillance
- Prognosis
- ROC Curve
- Survival Rate
- Time Factors
- Washington
Nearly half of all heart failure (HF) patients have diastolic HF (DHF) or clinical HF with normal or near-normal left ventricular ejection fraction (LVEF). Although the terminology has not been clearly defined, it is increasingly being referred to as HF with preserved ejection fraction (HFPEF). The prevalence of HFPEF increases with age, especially among older women. Identifying HFPEF is important because the etiology, pathogenesis, prognosis, and optimal management may differ from that for systolic HF (SHF) or HF with reduced ejection fraction. The clinical presentation of HF is similar for both SHF and HFPEF. As in SHF, HFPEF is a clinical diagnosis. Once a clinical diagnosis of HF has been made, the presence of HFPEF can be established by confirming a normal or near-normal LVEF, often by an echocardiogram. HFPEF is often associated with a history of hypertension, concentric left ventricular hypertrophy, vascular stiffness, and left ventricular diastolic dysfunction. As in SHF, HFPEF is also associated with poor outcomes. While therapies with angiotensin-converting enzyme inhibitors and beta-blockers improve outcomes in SHF, there is currently no such evidence of their benefits in older HFPEF patients. In this review recent advances in the diagnosis and management of HFPEF in older adults are discussed.
MeSH Terms
- Age Factors
- Aged
- Aged, 80 and over
- Aging
- Antihypertensive Agents
- Biomarkers, Pharmacological
- Cardiac Resynchronization Therapy
- Diuretics
- Echocardiography
- Electrocardiography
- Genetic Therapy
- Heart Failure, Diastolic
- Humans
- Stroke Volume
- Ventricular Function, Left
Obesity represents a low-grade inflammatory disease and appears a risk factor for insulin resistance, but little is known on whether this may contribute to the development of autoimmune inflammatory diseases. The aim of this work was to study the early-life diet-induced obesity in Lewis rats which are known to be highly susceptible to autoimmunity. Obesity was induced by reduced litter size (4 pups per litter) followed by high-fat diet (SHF rats). Control rats (8 pups per litter) were fed with standard diet (CN rats). Oral glucose tolerance test (3 g glucose per kg b.w.) was performed by intra-gastric tube in conscious rats after 12 h fast. Adipocyte size was assessed by light microscope after collagenase digestion. Hypothalamic arcuate (ARC) and paraventricular nuclei (PVN) were isolated by the punching technique. Target mRNAs were quantified by real-time PCR with the use of TaqMan probes and primers. Serum hormones (leptin, ghrelin, adiponectin, visfatin and insulin) were assayed by specific RIAs . During the experimental period SHF rats had the same body weight gain and caloric intake as CN rats. At the age of 8 weeks SHF rats showed increased epididymal fat mass and adipocyte volume, impaired glucose tolerance, normal basal fasting insulin, visfatin, and ghrelin level, but decreased adiponectin and high leptin level. In the ARC, the SHF rats showed increased expression of mRNA for orexigenic neuropeptide Y (NPY), agouti-related protein (AgRP) and anorexigenic pro-inflammatory cytokine IL-6. In the PVN, the SHF rats showed increased expression of mRNA for anorexigenic melanocortin 4 receptor (MC4R) and IL-6. Overexpression of orexigenic NPY and AgRP in the ARC indicates leptin resistance in SHF rats. The increased expression of MC4R in PVN points to the activation of melanocortin anorexigenic system which, along with increased hypothalamic IL-6, might prevent the animals from overfeeding. Higher adiposity in these rats results from the high fat-diet composition and not from increased caloric intake. Furthermore, enhanced leptin production appears the main factor indicating the predisposition to autoimmunity in these overfed rats.
MeSH Terms
- Adipocytes, White
- Adiponectin
- Adipose Tissue, White
- Adiposity
- Aging
- Agouti-Related Protein
- Analysis of Variance
- Animals
- Appetite Regulation
- Arcuate Nucleus of Hypothalamus
- Area Under Curve
- Body Weight
- Cell Size
- Dietary Fats
- Energy Intake
- Feeding Behavior
- Gene Expression
- Ghrelin
- Glucose Intolerance
- Insulin
- Interleukin-6
- Leptin
- Litter Size
- Male
- Neuropeptide Y
- Nicotinamide Phosphoribosyltransferase
- Obesity
- Paraventricular Hypothalamic Nucleus
- RNA, Messenger
- Rats
- Rats, Inbred Lew
- Receptor, Melanocortin, Type 4
Epidemiological and experimental studies have documented both the rising burden of diastolic heart failure (DHF) and several mechanisms that distinguish this disease from systolic heart failure (SHF). Controversies continue to surround the term 'DHF' as well as its existence as a pathophysiological entity distinct from SHF. Approximately half of all patients who present with heart failure have near-normal systolic function and predominately abnormal diastolic function. Recent reports counter the commonly held belief that survival of patients with DHF is better than that of patients with SHF. The challenges associated with managing the DHF phenotype arise from the heterogeneous etiologies of the condition that include aging, diabetes mellitus, hypertension and ischemia. Lack of diastolic distensibility in DHF has been attributed primarily to hypertrophy and fibrosis. Extracellular matrix and cytoskeletal components including matrix metalloproteinases, titin isoforms, and the quality and quantity of collagen are implicated in DHF development. Impaired active relaxation of the contractile apparatus also contributes to DHF. Novel therapeutic targets that address the pathophysiology of this disease are being actively explored, although as yet there are no proven therapies for DHF. New epidemiologic and mechanistic data regarding DHF highlight the urgency with which the scientific community must address this important public health problem.
MeSH Terms
- Aging
- Diabetes Mellitus
- Diagnosis, Differential
- Heart Failure, Diastolic
- Humans
- Hypertension
- Myocardial Ischemia
- Myocardium
- Stroke Volume
In Europe, 20% of the populations is over 65 years of age. About 5% of the older adults have heart failure. Heart failure (HF) in the elderly is an increasing public health problem, leading cause of hospitalization in older patients and a major cause of morbidity and mortality. Prognosis has improved only slightly during the past decade. Typically, heart failure occurs when ventricles do not fill (diastolic heart failure - DHF) or empty blood (systolic heart failure - SHF) properly. Transthoracic echocardiography is the key investigation to confirm the underlying structural and functional abnormalities of the heart. Patients with heart failure due to left ventricular systolic dysfunction should be treated with a diuretic, an angiotensin converting enzyme inhibitor, and a beta-blocker (unless contraindicated). Several epidemiologic studies have recently shown that more than 50% of older patients who present with symptoms of HF have DHF. While numerous large trials have established specific therapies for SHF, such trials are lacking for DHF. The finding of similar key pathophysiologic abnormalities in DHF and SHF suggests the possibility that therapies that have been successful for SHF may have a role in therapy for DHF. A recent survey showed that despite physicians' awareness of the benefits of beta-blocker therapy, only minority of patients with heart failure are treated with beta-blocker or combination of ACE inhibitors and beta-blocker.
MeSH Terms
- Adrenergic beta-Antagonists
- Age Factors
- Aged
- Aging
- Angiotensin-Converting Enzyme Inhibitors
- Cardiotonic Agents
- Controlled Clinical Trials as Topic
- Diuretics
- Echocardiography
- Europe
- Health Status
- Heart Failure
- Humans
- Research Design
- Risk Factors
- Vasodilator Agents
- Ventricular Dysfunction, Left
It is now clear that diastolic heart failure (DHF) is an important, perhaps even dominant form of heart failure in older Americans. However, our knowledge base regarding the epidemiology, pathophysiology, natural history, and therapy of this relatively recently recognized disorder is limited. A number of normal age related changes in the heart and vascular system may predispose to or lower the threshold for expression of DHF. Recent reports from large population-based observational studies indicate that over 50% of persons 65 years and older who have heart failure have normal LV systolic function (presumed DHF). Among these, 45% have no other confounding variables (coronary, valvular, or pulmonary disease) and meet the criteria for isolated DHF. DHF is substantially more common in older women than men. A history of systemic hypertension and left ventricular hypertrophy are almost invariably present. Mortality rates are about 50% lower in DHF than in systolic heart failure (SHF) when stable outpatients are considered. However, in hospitalized and very elderly patients, the mortality rate appears similar in DHF and SHF. Furthermore, due to its higher prevalence, the total mortality in the older population attributable to DHF exceeds that of SHF. Morbidity in DHF is substantial and approaches that of SHF. In the chronic setting, DHF patients can have severe exercise intolerance related to failure of the Frank-Starling mechanism with reduced peak cardiac output, heart rate, and stroke volume and increased LV filling pressure. DHF patients also appear to have increased vascular stiffness, accelerated systolic blood pressure response to exercise, neuroendocrine activation, and reduced quality of life. Acute exacerbations (pulmonary edema) frequently occur and are associated with severe hypertension, sodium indiscretion, and medication non-compliance. Surprisingly, overt myocardial ischemia appears to infrequently play a role in these acute exacerbations. Therapy is currently empiric and multicenter, randomized, controlled trials are urgently needed. Anecdotally, control of blood pressure appears to improve symptoms and reduce the frequency of acute exacerbations. In addition, non-pharmacologic intervention, including multi-disciplinary case management is useful.
MeSH Terms
- Aged
- Aging
- Diastole
- Female
- Heart Failure
- Humans
- Hypertension
- Hypertrophy, Left Ventricular
- Male
- Prognosis
- United States