Beta-adrenergic receptors in congestive heart failure: present knowledge and future directions

In recent years substantial information has become available on the function and regulation of beta-adrenergic receptors in experimental model systems and in the human heart. Beta-Adrenergic receptors mediate the positive inotropic and chronotropic effects of the sympathetic neurotransmitter norepinephrine in the heart. They can be altered in various disease states including congestive heart failure. In order to enhance understanding of beta-adrenergic receptor regulation in heart failure, we here review the present knowledge and the open question in three areas: (1) the differential role of beta 1- and beta 2-adrenergic receptors: (2) regulation of the number of cardiac beta-adrenergic receptors by drugs and disease states: and (3) regulation of the responsiveness of cardiac beta-adrenergic receptors.     

Cancer diagnosis in patients with heart failure: epidemiology,clinical implications and gaps in knowledge

Cancer and heart failure (HF) are common medical conditions with a steadily rising prevalence in industrialized countries, particularly in the elderly, and they both potentially carry a poor prognosis. A new diagnosis of malignancy in subjects with pre‐existing HF is not infrequent, and challenges HF specialists as well as oncologists with complex questions relating to both HF and cancer management. An increased incidence of cancer in patients with established HF has also been suggested. This review paper summarizes the epidemiology and the prognostic implications of cancer occurrence in HF, the impact of pre‐existing HF on cancer treatment decisions and the impact of cancer on HF therapeutic options, while providing some practical suggestions regarding patient care and highlighting gaps in knowledge.     

Silent myocardial infarction and risk of heart failure: Current evidence and gaps in knowledge

Coronary heart disease (CHD) is the most common underlying risk factor for heart failure (HF); up to one-third of the patients who are hospitalized for HF each year in the United States have a history of myocardial infarction (MI). Although silent MI (SMI) could account for up to one-half of all MIs, only a few studies examined the relationship between SMI and risk of HF. These few studies agreed on their conclusions that SMI is associated with increased risk of HF. However, there was less agreement on the magnitude of risk and the sex differences in the association between SMI and HF, which is probably due to the heterogeneity in how these studies defined SMI. This report summarizes and discusses the current evidence linking SMI to HF, the impact of the methods by which SMI is defined on the reported relationship between SMI and HF, the potential mechanisms for such relationship, the implications of these findings, and the gaps in knowledge that need to be addressed.     

Perioperative outcomes and risk assessment in dialysis patients: current knowledge and future directions

Perioperative medicine is rapidly emerging as a key discipline to address the specific needs of high‐risk surgical groups, such as those on chronic dialysis. Crude hospital separation rates for chronic dialysis patients are considerably higher than patients with normal renal function, with up to 15% of admission being related to surgical intervention. Dialysis dependency carries substantial mortality and morbidity risk compared to patients with normal renal function. This group of patients has a high comorbid burden and complex medical need, making accurate perioperative planning essential. Existing perioperative risk assessment tools are unvalidated in chronic dialysis patients. Furthermore, they fail to incorporate important dialysis treatment‐related characteristics that could potentially influence perioperative outcomes. There is a dearth of information on perioperative outcomes of Australasian dialysis patients. Current perioperative outcome estimates stem predominantly from North American literature; however, the generalisability of these findings is limited, as the survival of North American dialysis patients is significantly inferior to their Australasian counterparts and potentially confounds reported perioperative outcomes; let alone regional variation in surgical indication and technique. We propose that data linkage between high‐quality national registries will provide more complete data with more detailed patient and procedural information to allow for more informative analyses to develop and validate dialysis‐specific risk assessment tools.     

Hospitalization of patients with heart failure: a population-based study.

AIMS: To describe the clinical course of heart failure in a population-based sample of incident cases, and to identify factors predicting hospitalization and mortality. METHODS AND RESULTS: Three hundred and thirty-two incident cases were identified over 15 months; 208 inpatients and 124 outpatients. Thirty-eight inpatients died during the first hospital admission (case fatality 18%) leaving 294 at risk of subsequent hospitalization. Over an average follow-up of 19 months, 173 cases were hospitalized on 311 occasions. Two hundred and twenty-four (72%) of these admissions were unplanned, with 51% due to worsening heart failure. One hundred and ten cases died over the same period. Cases diagnosed as an inpatient had 26 more admissions for worsening heart failure per 100 cases during follow-up (95% CI 9 to 44) compared to cases diagnosed as an outpatient, and also a higher mortality (hazard ratio 3.1 (95% CI 1.9 to 5.1)). Age was the only factor associated with an increased risk of hospitalization for worsening heart failure, but age, functional class and serum creatinine were predictive of mortality. CONCLUSIONS: New cases of heart failure are at high risk of subsequent hospitalization, especially during the first months after diagnosis. Whilst predicting which patients will be hospitalized is difficult, interventions designed to reduce hospitalizations for worsening heart failure should be targeted at elderly inpatients with a new diagnosis.     

Enhanced external counterpulsation and future directions: step beyond medical management for patients with angina and heart failure

Between 25,000 and 75,000 new cases of angina refractory to maximal medical therapy and standard coronary revascularization procedures are diagnosed each year. In addition, heart failure also places an enormous burden on the U.S. health care system, with an estimated economic impact ranging from $20 billion to more than $50 billion per year. The technique of counterpulsation, studied for almost one-half century now, is considered a safe, highly beneficial, low-cost, noninvasive treatment for these angina patients, and now for heart failure patients as well. Recent evidence suggests that enhanced external counterpulsation (EECP) therapy may improve symptoms and decrease long-term morbidity via more than 1 mechanism, including improvement in endothelial function, promotion of collateralization, enhancement of ventricular function, improvement in oxygen consumption (VO2), regression of atherosclerosis, and peripheral training effects similar to exercise. Numerous clinical trials in the last 2 decades have shown EECP therapy to be safe and effective for patients with refractory angina with a clinical response rate averaging 70% to 80%, which is sustained up to 5 years. It is not only safe in patients with coexisting heart failure, but also is shown to improve quality of life and exercise capacity and to improve left ventricular function long-term. Interestingly, EECP therapy has been studied for various potential uses other than heart disease, such as restless leg syndrome, sudden deafness, hepatorenal syndrome, erectile dysfunction, and so on. This review summarizes the current evidence for its use in stable angina and heart failure and its future directions.     

Physical training as an adjunct therapy in patients with congestive heart failure: Patient selection, training protocols, results, and future directions

Exercise intolerance in patients with chronic heart failure (CHF) shows no correlation to the degree of left ventricular dysfunction. This surprising finding has directed attention to peripheral changes in CHF: reduced endothelium-dependent vasodilation and altered skeletal muscle metabolism. Physical exercise training has evolved as an important therapeutic approach to influence these noncardiac causes of exercise intolerance. It has been shown to enhance the oxidative capacity of the working skeletal muscle, to attenuate ergoreflex activity, to correct endothelial dysfunction, and to improve ventilation. All exercise-induced adaptations converge to increase peak oxygen uptake by up to 2 mL/kg.min^-1. Uncertainty remains concerning optimal patient selection, training protocol, and long-term effects on cardiac function. For patients experiencing stable CHF while on optimal cardiac medication, a combination of inhospital and home-based aerobic endurance training in combination with local muscle strength training seems most promising. Although exercise training offers no causal treatment of CHF, it has great potential as an adjunct therapy directed at improving exercise tolerance and expanding the physical limits of CHF patients.     

Enhanced external counterpulsation and future directions: step beyond medical management for patients with angina and heart failure.

Between 25,000 and 75,000 new cases of angina refractory to maximal medical therapy and standard coronary revascularization procedures are diagnosed each year. In addition, heart failure also places an enormous burden on the U.S. health care system, with an estimated economic impact ranging from $20 billion to more than $50 billion per year. The technique of counterpulsation, studied for almost one-half century now, is considered a safe, highly beneficial, low-cost, noninvasive treatment for these angina patients, and now for heart failure patients as well. Recent evidence suggests that enhanced external counterpulsation (EECP) therapy may improve symptoms and decrease long-term morbidity via more than 1 mechanism, including improvement in endothelial function, promotion of collateralization, enhancement of ventricular function, improvement in oxygen consumption (VO2), regression of atherosclerosis, and peripheral training effects similar to exercise. Numerous clinical trials in the last 2 decades have shown EECP therapy to be safe and effective for patients with refractory angina with a clinical response rate averaging 70% to 80%, which is sustained up to 5 years. It is not only safe in patients with coexisting heart failure, but also is shown to improve quality of life and exercise capacity and to improve left ventricular function long-term. Interestingly, EECP therapy has been studied for various potential uses other than heart disease, such as restless leg syndrome, sudden deafness, hepatorenal syndrome, erectile dysfunction, and so on. This review summarizes the current evidence for its use in stable angina and heart failure and its future directions.     

Sudden cardiac death risk factors in patients with heart failure treated with carvedilol

BACKGROUND: Chronic heart failure (CHF) is associated with a high risk of sudden cardiac death (SCD). Most frequently SCD occurs in patients with NYHA class II and III. AIM: To evaluate the influence of prolonged carvedilol therapy on SCD risk in CHF patients. METHODS: The study included 86 patients (81 men and 5 women) aged 56.8+/-9.19 (35-70) years with CHF in NYHA class II and III receiving an ACE inhibitor and diuretics but not beta-blockers. At baseline and after 12 months of carvedilol therapy the following risk factors for SCD were analysed: in angiography - occluded infarct-related artery; in echocardiography - left ventricular ejection fraction (LVEF) <30%, volume of the left ventricle (LVEDV) >140 ml; in ECG at rest - sinus heart rate (HRs) >75/min, sustained atrial fibrillation, increased QTc; in 24-hour ECG recording - complex arrhythmia, blunted heart rate variability (SDNN <100 ms) and abnormal turbulence parameters (TO and TS or one of them); in signal-averaged ECG - late ventricular potentials and prolonged fQRS >114 ms. The analysis of SCD risk factors in basic examination in patients who suddenly died was also performed. RESULTS: During one-year carvedilol therapy heart transplantation was performed in 2 patients; 5 patients died. At 12 months the following risk factors for SCD were significantly changed: HRs >75/min (50 vs. 16 patients, p=0.006), LVEF <30% (37 vs. 14 patients, p=0.01), SDNN <100 ms (19 vs. 9 patients, p=0.04). At 12 months the number of risk factors for SCD in each patient was significantly reduced (p=0.001). In patients who suddenly died we found a greater amount of SCD risk factors in basic examination (7 vs. 5) as compared to alive patients. CONCLUSIONS: Prolonged beta-adrenergic blockade reduces risk of sudden cardiac death through significant LVEF increase, reduction of HR at rest and improvement of HRV.     

Primary biliary cirrhosis: current knowledge, perspectives, and future directions

These perspectives from the first International Symposium on Primary Biliary Cirrhosis review recent advances and single out some areas for further enquiry. The latter include frequency and type of associated autoimmune diseases, the existence of clinical subsets of PBC, immunohistochemical analysis of lymphoid infiltrates in the liver, effects of immunosuppressive and other treatment regimens, and models for predicting the optimal time for liver transplantation. The M2 autoantigens have been identified as mitochondrial 2-oxo-acid dehydrogenase enzymes. These include pyruvate dehydrogenase (70-74 kd antigen) and branched chain 2-oxo-acid dehydrogenase and 2-oxo-acid glutaric dehydrogenase (45-52 kd antigens). Each of these enzymes has three subunits, E1 to E3. For PDH, an autoepitope has been identified as a decapeptide containing the attachment site of lipoic acid, an essential cofactor for enzyme activity. Current questions include the degree to which antibodies to PDH, and related enzymes, account for the mitochondrial reactivity defined by immunofluorescence or other procedures, the cell-surface expression of M2 autoantigens, and the significance of the occurrence of nonmitochondrial (such as centromeric) autoantibodies in PBC. The unknown T lymphocyte contribution to the autoimmune response in PBC may involve inducer and effector components. A postulated T-cell autoepitope may be presented, in association with MHC class I or class II molecules, on the surface of biliary epithelial cells. T cell lines from PBC livers removed during transplantation could provide data on the T-lymphocyte contribution to the pathogenesis of PBC.     

慢性心力衰竭患者肾功能恶化的危险因素分析

目的 研究慢性心力衰竭(心衰)患者肾功能恶化的危险因素及其对预后的影响.方法 采用病例对照研究方法,分析与肾功能恶化发生有统计学关联的独立危险因素,同时观察肾功能恶化对预后的影响.结果 住院心衰患者肾功能恶化发生率31%,入院肌酐水平及心功能分级与肾功能恶化的发生独立相关,OR值分别为2.248(95%CI1.088～4.647,P=0.029)和2.485(95%CI1.385～4.459.P＝0.002).发生肾功能恶化的患者住院期间病死率明显高于对照组(16.7%比2.1%,P=0.000),调整混杂因素后,肾功能恶化是死亡的独立危险因素,OR值3.824(95%CI2.452～5.137.P＜0.015).结论 肾功能恶化在住院心衰患者中发生率较高,与住院期间病死率明显相关.入院肌酐水平偏高及心功能差为发生肾功能恶化的独立危险因素.

Abstract：

Objective To investigate the risk factors of worsening renal function (WRF) in patients with chronic heart failure ( CHF) and WRF influence on prognosis. Methods A case-control study were undertaken to analyze independent risk factor statistically related to incidence of WRF, and to assess the influence of WRF on prognosis. Results The independent predictors of WRF were creatinine level at admission (OR 2.248,95% CI 1.088-4.647, P = 0.029) and NYHA class on admission ( OR 2.485, 95% CI 1.3854. 459, P = 0.002). The mortality of patient with WRF was obviously higher than that of control group during hospitalization( OR 3. 824,95% CI 2. 452-5. 637 ,P ＜0.015). Conclusions WRF is a common complication among patients hospitalized for CHF, and is obviously associated with mortality during hospitalization. Higher creatinine level and weak heart function are independent risk factors for incidence of WRF of patients with CHF.     

Reverse epidemiology of conventional cardiovascular risk factors in patients with chronic heart failure

Traditional risk factors of a poor clinical outcome and mortality in the general population, including body mass index (BMI), serum cholesterol, and blood pressure (BP), are also found to relate to outcome in patients with chronic heart failure (CHF), but in an opposite direction. Obesity, hypercholesterolemia, and high values of BP have been demonstrated to be associated with greater survival among CHF patients. These findings are in contrast to the well-known associations of over-nutrition, hypercholesterolemia, and hypertension with a poor outcome in the general population. The association between traditional cardiovascular risk factors and an adverse clinical outcome in CHF patients is referred to as "reverse epidemiology." The mechanisms for this inverse association in CHF is not clear. There are other populations with a similar risk factor reversal phenomenon, including patients with end-stage renal disease receiving dialysis, those with advanced malignancies, and individuals with advanced age. Several possible causes are hypothesized: the time discrepancy of the competing risk factors may play a role; the presence of the "malnutrition-inflammation complex syndrome" in CHF patients may explain the existence of reverse epidemiology; and a decreased level of lipoprotein molecules may distort their endotoxin-scavenging role, predisposing CHF patients with a low serum cholesterol level to inflammatory consequences of endotoxemia. It is possible that new goals for such traditional risk factors as BMI, serum cholesterol, and BP should be developed for CHF. Reverse epidemiology of conventional cardiovascular risk factors is observed in CHF and may have a bearing on the management of these patients; thus, it deserves further investigation.