Intervention In Congestive Heart Failure Research Articles

Effects of a collaborative health management model on peoplewith congestive heart failure: A systematic review and meta-analysis.

To determine the effects of collaborative health management of congestive heart failure through the rigorous evaluation and extraction of evidence. Over the past two decades, cardiovascular disease has been the leading cause of death worldwide. Multidisciplinary team intervention for congestive heart failure has increased with population ageing and congestive heart failure incidence rate as well as cost of care. However, the effectiveness and feasibility of collaborative health management need to be explored. Systematic review and meta-analysis. We conducted systematic literature searches in the Cochrane Library, PubMed, CINAHL and Medline for articles published between 2002 and 2022. After screening based on the inclusion and exclusion criteria, 13 articles were included in a rigorous review and evidence extraction process, evaluated methodological quality using the Jadad Quality Scale. Statistical heterogeneity was evaluated using Review Manager (RevMan Version 5.4) for the meta-analysis. In this study, a systematic review and meta-analysis were performed on 13 studies regarding the collaborative health management of people with congestive heart failure. The common result is that the collaborative health management model enables the enhancement of self-care and monitoring abilities, the strengthening of cardiac function, the alleviation of physiological and psychological symptoms and the improvement of readmission rates, mortality rate and quality of life. The congestive heart failure collaborative health management model could decrease the hospitalization rate related to congestive heart failure, all-cause mortality rate, and all-cause hospitalization rate, and improve the quality of life. The collaborative health management model could effectively coordinate interdisciplinary team cooperation and provide information, which decreases hospitalization and mortality risks and improves their quality of life. Our paper is a systematic review and meta-analysis, and such details do not apply to our work. WHAT DOES THIS PAPER CONTRIBUTE TO THE WIDER GLOBAL CLINICAL COMMUNITY?: The Collaborative Health Management Model provides in-depth insights, aiding in the design tailored to the specific circumstances of each country. Highlighting its critical role in the context of a global shortage of nursing staff, the model emphasizes the integration of multidisciplinary professional roles and the strengthening of collaboration as essential elements in addressing challenges posed by workforce shortages. Implementation of the Collaborative Health Management Model not only enhances patient care outcomes but also relieves pressure on healthcare systems, lowers medical costs, and addresses challenges arising from the shortage of nursing staff. Consequently, this model not only contributes to individual patient care improvement but also holds broader implications for enhancing the efficiency and sustainability of global healthcare systems. The detailed study protocol can be found on the PROSPERO website.

Reducing rates of readmission and development of an outpatient management plan in pulmonary hypertension: lessons from congestive heart failure management

Pulmonary hypertension currently has minimal guidelines for outpatient disease management. Congestive heart failure studies, however, have shown effectiveness of disease management plans in reducing all-cause mortality and all-cause and congestive heart failure-related hospital readmissions. Heart failure exacerbation is a common reason for readmission in both pulmonary hypertension and congestive heart failure. Our aim was to review individual studies and comprehensive meta-analyses to identify effective congestive heart failure interventions that can be used to develop similar disease management plans for pulmonary hypertension. A comprehensive literature review from 1993 to 2019 included original articles, systematic reviews, and meta-analyses. We reviewed topics of outpatient congestive heart failure interventions to decrease congestive heart failure mortality and readmission and patient management strategies in congestive heart failure. The most studied interventions included case management, multidisciplinary intervention, structured telephone strategy, and tele-monitoring. Case management showed decreased all-cause mortality at 12 months, all-cause readmission at 12 months, and congestive heart failure readmission at 6 and 12 months. Multidisciplinary intervention resulted in decreased all-cause readmission and congestive heart failure readmission. There was some discrepancy on effectiveness of tele-monitoring programs in individual studies; however, meta-analyses suggest tele-monitoring provided reduced all-cause mortality and risk of congestive heart failure hospitalization. Structured telephone strategy had similar results to tele-monitoring including decreased risk of congestive heart failure hospitalization, without effect on mortality. Extrapolating from congestive heart failure data, it seems strategies to improve the health of pulmonary hypertension patients and development of comprehensive care programs should include structured telephone strategy and/or tele-monitoring, case management strategies, and multidisciplinary interventions.

A Study of Vitamin D Supplementation to Patients with Chronic Diseases Admitted to Ain Shams University Hospital

Background: Vitamin D deficiency and insufficiency have become a common problem worldwide. Vitamin D has been associated with all causes of mortality in chronic diseases which are significantly associated with a longer hospital stay and poor outcome. Objectives: We aimed to investigate the role of empirical vitamin D supplementation in hospitalized patients and its relation to the length of stay and outcome of hospitalization. Study design: Case control study performed on eighty patients admitted to Internal Medicine Department at Ain Shams University Hospital, with acute deterioration of their chronic illness. Two groups of diseases were included, chronic liver diseases (CLD) and congestive heart failure (CHF). Methods: Twenty patients of each group were given vitamin D 200,000 IU IM within 3 days of admission (Intervention group) and 20 patients of each group (control group) did not receive vitamin D. Patients were sampled for their vitamin D, calcium and phosphorus levels on admission prior to intervention. Results: CLD and CHF Intervention groups had a non-significant correlation between vitamin D supplementation with length of hospital stay and mortality in comparison with control groups (P =1.000) (p=0.823) respectively. On the other hand, we found baseline vitamin D deficiency was an independent predictor of mortality (P value .018). Conclusions: Vitamin D deficiency is significantly associated with longer hospital stay and poor outcome of hospital admission. Beneficial effect of empirical vitamin D supplementation can't be achieved with single dose vitamin D (200,000 IU) on CHF and CLD hospitalized patients.

Pyruvate enhancement of cardiac performance: Cellular mechanisms and clinical application.

Cardiac contractile function is adenosine-5'-triphosphate (ATP)-intensive, and the myocardium's high demand for oxygen and energy substrates leaves it acutely vulnerable to interruptions in its blood supply. The myriad cardioprotective properties of the natural intermediary metabolite pyruvate make it a potentially powerful intervention against the complex injury cascade ignited by myocardial ischemia-reperfusion. A readily oxidized metabolic substrate, pyruvate augments myocardial free energy of ATP hydrolysis to a greater extent than the physiological fuels glucose, lactate and fatty acids, particularly when it is provided at supra-physiological plasma concentrations. Pyruvate also exerts antioxidant effects by detoxifying reactive oxygen and nitrogen intermediates, and by increasing nicotinamide adenine dinucleotide phosphate reduced form (NADPH) production to maintain glutathione redox state. These enhancements of free energy and antioxidant defenses combine to augment sarcoplasmic reticular Ca2+ release and re-uptake central to cardiac mechanical performance and to restore β-adrenergic signaling of ischemically stunned myocardium. By minimizing Ca2+ mismanagement and oxidative stress, pyruvate suppresses inflammation in post-ischemic myocardium. Thus, pyruvate administration stabilized cardiac performance, augmented free energy of ATP hydrolysis and glutathione redox systems, and/or quelled inflammation in a porcine model of cardiopulmonary bypass, a canine model of cardiac arrest-resuscitation, and a caprine model of hypovolemia and hindlimb ischemia-reperfusion. Pyruvate's myriad benefits in preclinical models provide the mechanistic framework for its clinical application as metabolic support for myocardium at risk. Phase one trials have demonstrated pyruvate's safety and efficacy for intravenous resuscitation for septic shock, intracoronary infusion for heart failure and as a component of cardioplegia for cardiopulmonary bypass. The favorable outcomes of these trials, which argue for expanded, phase three investigations of pyruvate therapy, mirror findings in isolated, perfused hearts, underscoring the pivotal role of preclinical research in identifying clinical interventions for cardiovascular diseases. Impact statement This article reviews pyruvate's cardioprotective properties as an energy-yielding metabolic fuel, antioxidant and anti-inflammatory agent in mammalian myocardium. Preclinical research has shown these properties make pyruvate a powerful intervention to curb the complex injury cascade ignited by ischemia and reperfusion. In ischemically stunned isolated hearts and in large mammal models of cardiopulmonary bypass, cardiac arrest-resuscitation and hypovolemia, intracoronary pyruvate supports recovery of myocardial contractile function, intracellular Ca2+ homeostasis and free energy of ATP hydrolysis, and its antioxidant actions restore β-adrenergic signaling and suppress inflammation. The first clinical trials of pyruvate for cardiopulmonary bypass, fluid resuscitation and intracoronary intervention for congestive heart failure have been reported. Receiver operating characteristic analyses show remarkable concordance between pyruvate's beneficial functional and metabolic effects in isolated, perfused hearts and in patients recovering from cardiopulmonary bypass in which they received pyruvate- vs. L-lactate-fortified cardioplegia. This research exemplifies the translation of mechanism-oriented preclinical studies to clinical application and outcomes.

Reducing Rates of Readmission and Development of an Outpatient Management Plan in Pulmonary Hypertension: Lessons From Congestive Heart Failure Management

SESSION TITLE: Pulmonary Vascular Disease I SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, October 26, 2016 at 01:30 PM - 02:30 PM PURPOSE: Pulmonary Hypertension (PH) is a progressive group of diseases that remains difficult to treat and carries significant morbidity and mortality despite available medical therapy. There are currently minimal guidelines on chronic outpatient management and prevention of hospitalization owing to the low number of patients and orphan status of the disease. In contrast, congestive heart failure (CHF) outpatient management interventions have been investigated in multiple trials. A common reason for admission in PH and CHF is heart failure exacerbation. The disease states share similar dietary and fluid management challenges, disease management and compliance issues. CHF has well established intervention models that have successfully decreased hospital readmission rates and mortality. We aimed to analyze outpatient CHF disease management interventions that have shown reductions in hospital readmissions and mortality as a starting point for developing an outpatient pulmonary hypertension intervention and management plan. METHODS: A comprehensive review of literature was performed, including original trials and meta-analysis and reviews. We reviewed the topics of outpatient CHF interventions to decrease CHF mortality and readmission and patient management strategies in CHF. RESULTS: The most studied interventions included case management (CM-specialist nurse driven, education pre/post discharge, specialist nurse home visits, scheduled telephone calls for symptom management, when to seek help), multidisciplinary Intervention ( MI-coordinated interventions and communications; specialist nurse driven, patient-caregiver education regarding disease, medication and diet, nurse clinic visits, regular telephone calls, individualized follow-up plan, access to physician, nurse, dietician, pharmacist, social worker), remote monitoring programs consisting of structured telephone strategy (STS-monitoring collected data via human-human or human-machine interactive response system) or tele-monitoring (TM-physiologic data transmission of EKG, blood pressure, weight, respiratory rate digitally). Clinic visits did not have a significant effect on CHF readmission or mortality. CM showed decreased all-cause mortality (ACM) at 12 months, all-cause readmission (ACR) at 12 months and CHF readmission at 6 and 12 months. MI resulted in decreased ACR and CHF readmission. There was some discrepancy on effectiveness of TM programs alone in individual studies, however large meta-analysis suggests TM provided a reduction in ACM and risk of CHF hospitalization. STS had similar results to TM including decreased risk of CHF hospitalization, without an effect on mortality. CONCLUSIONS: Extrapolating from CHF data, it seems that strategies to improve the health of PH patients should include structured telephone strategy and/ or tele-monitoring, case management strategies and multi-disciplinary interventions. CLINICAL IMPLICATIONS: There is no consensus on the most effective outpatient management of PH or strategies to reduce hospital readmission. Successful CHF interventions can provide us with a starting point as we aim to develop and validate PH specific interventions. DISCLOSURE: The following authors have nothing to disclose: Justin Dolan, Viviana Navas, James Tarver, Jinesh Mehta, Franck Rahaghi No Product/Research Disclosure Information

An agent-based simulation model to study accountable care organizations

Creating accountable care organizations (ACOs) has been widely discussed as a strategy to control rapidly rising healthcare costs and improve quality of care; however, building an effective ACO is a complex process involving multiple stakeholders (payers, providers, patients) with their own interests. Also, implementation of an ACO is costly in terms of time and money. Immature design could cause safety hazards. Therefore, there is a need for analytical model-based decision-support tools that can predict the outcomes of different strategies to facilitate ACO design and implementation. In this study, an agent-based simulation model was developed to study ACOs that considers payers, healthcare providers, and patients as agents under the shared saving payment model of care for congestive heart failure (CHF), one of the most expensive causes of sometimes preventable hospitalizations. The agent-based simulation model has identified the critical determinants for the payment model design that can motivate provider behavior changes to achieve maximum financial and quality outcomes of an ACO. The results show nonlinear provider behavior change patterns corresponding to changes in payment model designs. The outcomes vary by providers with different quality or financial priorities, and are most sensitive to the cost-effectiveness of CHF interventions that an ACO implements. This study demonstrates an increasingly important method to construct a healthcare system analytics model that can help inform health policy and healthcare management decisions. The study also points out that the likely success of an ACO is interdependent with payment model design, provider characteristics, and cost and effectiveness of healthcare interventions.

Oncologists' and family physicians' views on value for money of cancer and congestive heart failure care.

BackgroundPrevious studies suggest that cancer-related interventions are valued by policy makers more favorably than interventions for other medical conditions, but the views of practicing physicians have not yet been assessed in Israel. Attitudes and judgments of practicing physicians may assist decision-makers in their deliberations on coverage of new technologies. We conducted a national survey in Israel among oncologists and family physicians to explore their views on access to care, coverage decisions and treatment recommendations for cancer and congestive heart failure (CHF) patients.MethodsWe administered a web-based survey to 300 family physicians and 156 oncologists. The questionnaire included 24 statements and physicians were asked to indicate their level of agreement with each statement on a 5-point Likert scale, ranging from “strongly agree” to “strongly disagree”. Where relevant, physicians were asked to express their views on interventions for cancer and CHF respectively.ResultsResponse rates were 39% for family physicians and 36% for oncologists. Participants expressed similar views on cancer and CHF care and no significant differences were found between the two medical specialties. More than 85% of physicians believe that inclusion of a treatment in the National List of Health Services (NLHS) strongly affects their patients’ access to care. Approximately 80% suggest that more use of comparative-effectiveness and cost-effectiveness analysis is needed in coverage decisions. The vast majority of respondents (75%) suggest that assessment of value-for-money should be made by an independent (academic) institution or the national committee responsible for recommending coverage decisions, Seventy percent believe that treatments not included in the NLHS should be included in supplementary health insurance programs and only a small minority of respondents (<30%) believe that cancer-related interventions should receive higher priority than non-cancer interventions in coverage decisions.ConclusionsOur findings suggest that both oncologists and family physicians value cancer and CHF interventions equally. We could not find evidence for a “cancer premium” as implied from previous surveys and analysis of coverage decisions in various countries.

Which Is More Valuable, Longer Survival or Better Quality of Life? Israeli Oncologists’ and Family Physicians’ Attitudes Toward the Relative Value of New Cancer and Congestive Heart Failure Interventions

ObjectivesWe determined how Israeli oncologists and family physicians value life-prolongation versus quality-of-life (QOL)-enhancing outcomes attributable to cancer and congestive heart failure interventions. MethodsWe presented physicians with two scenarios involving a hypothetical patient with metastatic cancer expected to survive 12 months with current treatment. In a life-prolongation scenario, we suggested that a new treatment increases survival at an incremental cost of $50,000 over the standard of care. Participants were asked what minimum improvement in median survival the new therapy would need to provide for them to recommend it over the standard of care. In the QOL-enhancing scenario, we asked the maximum willingness to pay for an intervention that leads to the same survival as the standard treatment, but increases patient’s QOL from 50 to 75 (on a 0–100 scale). We replicated these scenarios by substituting a patient with congestive heart failure instead of metastatic cancer. We derived the incremental cost-effectiveness ratio per quality-adjusted life-year (QALY) gained threshold implied by each response. ResultsIn the life-prolongation scenario, the cost-effectiveness thresholds implied by oncologists were $150,000/QALY and $100,000/QALY for cancer and CHF, respectively. Cost-effectiveness thresholds implied by family physicians were $50,000/QALY regardless of the disease type. Willingness to pay for the QOL-enhancing scenarios was $60,000/QALY and did not differ by physicians’ specialty or disease. ConclusionsOur findings suggest that family physicians value life-prolonging and QOL-enhancing interventions roughly equally, while oncologists value interventions that extend survival more highly than those that improve only QOL. These findings may have important implications for coverage and reimbursement decisions of new technologies.

The E-Coach transition support computer telephony implementation study: Protocol of a randomized trial

BackgroundPatients requiring complex care are at high risk during the transition from one setting of care to another. Effective interventions to support care transitions have been designed but are very resource intensive. Telemonitoring has been considered as an approach to enhance care transition support, but many telemonitoring systems require special equipment or web-based interfaces to interact with patients and caregivers. Methods/designIn this paper we report our protocol for developing and testing E-Coach, an interactive voice response (IVR)-enhanced care transition intervention that monitors patients at home using their personal phone. The elements described include 1) development of an IVR monitoring system that will be based on Coleman's four pillars of care transition support; 2) development of a web-based “dashboard” of IVR responses that alert care transition nurses (CTN) of patient/caregiver concerns after discharge and allow documentation by the CTN when patients/caregivers are called; 3) pilot testing of the IVR system by patients and providers with refinement of the system based on patient/provider input; and 4) a pragmatic protocol for formal testing through a randomized controlled trial (RCT) of the E-Coach intervention in congestive heart failure (CHF) and chronic obstructive pulmonary disease (COPD) patients admitted to a large tertiary hospital. Trial Registration: CT.gov#: NCT01135381.

The importance of organizational characteristics for improving outcomes in patients with chronic disease: a systematic review of congestive heart failure

BackgroundDespite applications of models of care and organizational or system-level interventions to improve patient outcomes for chronic disease, consistent improvements have not been achieved. This may reflect a mismatch between the interventions and the nature of the settings in which they are attempted. The application of complex adaptive systems (CAS) framework to understand clinical systems and inform efforts to improve them may lead to more successful interventions. We performed a systematic review of interventions to improve outcomes of patients with congestive heart failure (CHF) to examine whether interventions consistent with CAS are more likely to be effective. We then examine differences between interventions that are most effective for improving outcomes for patients with CHF versus previously published data for type 2 diabetes to explore the potential impact of the nature of the disease on the types of interventions that are more likely to be effective.MethodsWe conducted a systematic review of the literature between 1998 and 2008 of organizational interventions to improve care of patients with CHF. Two independent reviewers independently assessed studies that met inclusion criteria to determine whether each reported intervention reflected one or more CAS characteristics. The effectiveness of interventions was rated as either 0 (no effect), 0.5 (mixed effect), or 1.0 (effective) based on the type, number, and significance of reported outcomes. Fisher's exact test was used to examine the association between CAS characteristics and intervention effectiveness. Specific CAS characteristics associated with intervention effectiveness for CHF were contrasted with previously published data for type 2 diabetes.Results and discussionForty-four studies describing 46 interventions met eligibility criteria. All interventions utilized at least one CAS characteristic, and 85% were either 'mixed effect' or 'effective' in terms of outcomes. The number of CAS characteristics present in each intervention was associated with effectiveness (p < 0.001), supporting the idea that interventions consistent with CAS are more likely to be effective. The individual CAS characteristics associated with CHF intervention effectiveness were learning, self-organization, and co-evolution, a finding different from our previously published analysis of interventions for diabetes. We suggest this difference may be related to the degree of uncertainty involved in caring for patients with diabetes versus CHF.ConclusionThese results suggest that for interventions to be effective, they must be consistent with the CAS nature of clinical systems. The difference in specific CAS characteristics associated with intervention effectiveness for CHF and diabetes suggests that interventions must also take into account attributes of the disease.

Hepatic Infantile Hemangioendothelioma with Unusual Manifestations

Hepatic Infantile Hemangioendothelioma with Unusual Manifestations

454 Multidisciplinary intervention in congestive heart failure ? does it reduce?

454 Multidisciplinary intervention in congestive heart failure ? does it reduce?

Specialist Nurse-Led Intervention in Outpatients with Congestive Heart Failure

Congestive heart failure (CHF) encompasses a spectrum of clinical syndromes and presentations. It affects 1–2% of the population in the UK and is associated with significant mortality which is comparable to most cancers. It accounts for more than 5% of adult medical admissions in the UK, with significant annual re-admission rates. Improved understanding of the pathophysiology of CHF has resulted in significant advancements in CHF management. Current pharmacologic agents, such as ACE inhibitors, β-adrenoceptor antagonists and spironolactone, influence symptoms and improve mortality. Despite this, many patients still require hospitalization. Multiple, potentially reversible factors are involved which, if addressed effectively, may result in significant reductions in re-admission rates. Patients with CHF often have other conditions, such as respiratory disease, resulting in prolonged lengths of stay. Suboptimal care and failure to adhere to management guidelines is also a preventable cause for re-admission. There has been an increasing need to develop adjunctive, non-pharmacologic strategies for managing CHF, which are designed to improve the patient’s functional status and quality of life. Key elements include systematic follow-up care and patient education. The concept of intensive outpatient or home-based CHF intervention has been developed and extensively evaluated in several randomized controlled trials. Early studies were inconclusive but provided an indication that discharge planning and home-based education are valuable strategies. Recently, an increasing number of studies utilizing the CHF nurse practitioner have provided positive results for non-pharmacologic intervention and demonstrate the potential of these interventions to reduce admissions to hospital by up to 50%. These studies had specific inclusion criteria and could not be generalized to the CHF population as a whole. The Study to Evaluate the effectiveness of Nurse-led Intervention in the management of outpatients with heart Failure (SENIF) explored whether a similar approach to CHF management was beneficial in a typical outpatient population of patients with CHF. Over 12 months, fewer intervention group patients required admission, resulting in 69% fewer hospital days. Cost effectiveness of nurse-led intervention has been suggested in several studies including SENIF, resulting from reduced hospitalizations and re-admissions, which vastly outweighed the modest increase in expenditure required to run the programs. Hospitalizations because of CHF impact greatly on limited healthcare resources. Specialist nurse-led intervention in CHF is a cost-effective, non-pharmacological strategy to help optimize CHF management.

Home-based intervention in congestive heart failure: long-term implications on readmission and survival

Home-based intervention in congestive heart failure: long-term implications on readmission and survival

Observations from a home-based congestive heart failure intervention

Observations from a home-based congestive heart failure intervention

Dobutamine as bridge to angiotensin-converting enzyme inhibitor-nitrate therapy in endstage heart failure.

Intravenous inotropic intervention in congestive heart failure is generally associated with a poor prognosis and is largely used as a "bridge" to mechanical support or heart transplantation. We hypothesized that the inotropic support afforded by dobutamine may serve as a bridge to the introduction and intensification of angiotensin-converting enzyme (ACE) inhibitor-nitrate therapy. We studied the efficacy of transitioning inotrope-dependent patients in endstage heart failure from intravenous dobutamine to high-dose ACE inhibitor-nitrates, with 1-year follow-up. Forty-nine sequential dobutamine-dependent patients with left ventricular ejection fraction (LVEF) 17+/-17% were treated with increasing lisinopril (1.9+/-1.5 to 46+/-28 mg/day) and isosorbide dinitrate (7+/-6 to 229+/-161 mg/day). Outpatient dobutamine was continued or repeat infusions pursued, as indicated, and dobutamine was tapered when feasible. During the following year, 14 of 49 patients required repeat dobutamine, with home treatment with dobutamine for 6.3+/-3.7 months (n = 5). At 1 year, New York Heart Association (NYHA) classification improved from 3.6+/-0.5 to 1.9+/-1.0, p < 0.0001; yearly hospitalizations fell from 2.7+/-2.3 to 1.2+/-3.0, p = 0.02; and LVEF rose from 17+/-7% to 24+/-11%, p < 0.0001. At 1 year, 14 patients who remained dobutamine dependent had significantly more severe symptoms than dobutamine-independent patients (n = 35). Transplant or death occurred in 7 of 14 patients with follow-up dobutamine, and in 5 of 35 patients free of subsequent dobutamine, p = 0.03. Patients with poor outcome (transplant n = 10, death n = 12) continued to be more limited (NYHA 2.7+/-0.9 vs. 1.7+/-0.9, p = 0.0002), with more follow-up hospitalizations (3.6+/-5.4 vs. 0.6+/-0.8, p = 0.0004), and no improvement in LVEF (17+/-8vs. 28+/-11%, p = 0.003). Of the patients on dobutamine inotropic support, 70% were successfully transitioned to ACE inhibitor-nitrate therapy, with improved symptoms and LVEF, and with reduced hospitalizations and follow-up dobutamine or transplant. Thirty percent of patients with continued need for dobutamine had a significantly poorer 1-year clinical outcome.

Specialist Nurses Improve Heart Failure Outcomes

Congestive heart failure (CHF), a large public health problem, is not managed optimally in many patients. Studies showing that specialist nurses can improve management of other chronic diseases led to this randomized controlled trial of a nursing intervention for CHF. Researchers enrolled 165 Scottish patients who were …

Adenosine inhibits lipopolysaccharide-induced secretion of tumor necrosis factor-alpha in the failing human heart.

The proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) has been implicated in the pathogenesis of congestive heart failure. Recent studies have shown that adenosine inhibits lipopolysaccharide (LPS)-induced expression of TNF-alpha in macrophages and rat cardiomyocytes. The aim of this study was to determine whether adenosine has a similar effect in the failing human heart. Left ventricular muscle strips were obtained from seven patients with end-stage congestive heart failure undergoing heart transplantation or insertion of a left ventricular assist device. The muscle strips were incubated at 37 degrees C in 95% O2/5% CO2 and stimulated with LPS (10 microg/mL). TNF-alpha release in the supernatant was measured with ELISA, and muscle sections were stained for TNF-alpha. Muscle strips released TNF-alpha in the absence of LPS (0.22+/-0.05 pg x mL(-1) x mg wet wt[-1]). TNF-alpha was immunolocalized to the cardiac myocyte, suggesting that the myocyte is a source for TNF-alpha production. Adenosine (10 micromol/L) decreased TNF-alpha by 40% (P<.05). The selective adenosine A2 receptor agonist DPMA (10 micromol/L) decreased TNF-alpha release by 87% (P<.001), whereas ITu (10 micromol/L), an adenosine-regulating agent that increases endogenous adenosine concentration, inhibited TNF-alpha release by 93% (P<.001). Adenosine can significantly diminish TNF levels in the failing human heart and may represent a new pharmacological intervention in congestive heart failure.

Adenosine Inhibits Lipopolysaccharide-Induced Cardiac Expression of Tumor Necrosis Factor-α

Tumor necrosis factor-alpha (TNF-alpha) is elevated in the failing heart. Very little is known about regulation of TNF-alpha in cardiomyocytes. TNF-alpha expression by macrophages is diminished by adenosine. Therefore, we hypothesized that a similar mechanism might occur in the heart. Neonatal rat myocytes were stimulated with lipopolysaccharide (LPS), and TNF-alpha was measured by ELISA. In the absence of LPS, myocytes did not release TNF-alpha in the medium. After exposure to LPS, TNF-alpha increased to 70.1+/-3.5 pg/mL at 6 hours. Immunofluorescent staining confirmed that TNF-alpha was expressed in myocytes. Adenosine decreased TNF-alpha in a dose-dependent manner (1 to 100 micromol/L, 37% to 65% decrease, P<.01). Adenosine also decreased TNF-alpha in cell homogenates by 78% (P<.0001). The effect of adenosine could be replicated by the A2 agonist PD-125944 (DPMA), by cAMP agonists 8-bromo-cAMP, forskolin, and Ro 20-1724, but not by A1 and A3 agonists. Conversely, the effect of adenosine could be suppressed by the adenylate cyclase inhibitor MDL-12,330. Adenosine also inhibited TNF-alpha in adult rat ventricular myocytes (-60%, P<.005) and rat papillary muscles (-55%, P<.05). In neonatal myocytes, adenosine normalized LPS-induced calcium changes and improved LPS-induced negative inotropic (P<.01) and negative lusitropic (P<.01) effects. Our results demonstrate that adenosine can significantly diminish TNF-alpha levels in the heart. The effect appears to be mediated by the A2 receptor and transduced through a G protein-adenylyl cyclase pathway. These results may explain some cardioprotective effects of adenosine and provide a novel pharmacological intervention in congestive heart failure.

Effects of methylprednisolone on hemodynamics and beta-adrenergic receptor signaling in rabbits with acute left ventricular failure.

Studies suggest that corticosteroids may restore the responsiveness to catecholamines in hypotensive patients. Since the significance of this promising intervention in congestive heart failure remains to be explored, we determined the effects of methylprednisolone, a potent activator of beta-adrenergic receptor signaling, on hemodynamics and beta-adrenergic receptor regulation in an animal model of heart failure. Acute left ventricular overloading was produced by aortic regurgitation (AR) in 22 Japanese white rabbits. Eleven animals received an intravenous administration of methylprednisolone (AR + PSL), while 11 received saline (AR + C) for 1 week. A sham operation was performed on 10 other rabbits (S). There was no difference between the AR + C and AR + PSL groups in the decrease in aortic diastolic pressure immediately after the production of AR. The aortic diastolic pressure and regurgitant fractions were also similar in the two groups. The left ventricular end-diastolic and end-systolic dimensions were both larger, and the left ventricular end-diastolic pressure was higher in AR + C or AR + PSL than in S rabbits. Between the AR + C and AR + PSL, there were no differences in any of these variables. Cardiac output was lower in AR + C, but not in AR + PSL, than in S. Cardiac output in AR + PSL was significantly higher than in AR + C. The myocardial concentration of norepinephrine and the number of beta-adrenergic receptors were both lower in the AR + C and AR + PSL than in the S groups. The number of receptors in AR + PSL was higher than in AR + C. Maximal isoproterenol-stimulated adenylyl cyclase activity was similar in the AR + C and AR + PSL groups. Results suggest methylprednisolone yielded some benefits, including an increase in cardiac output and in total beta-adrenergic receptor number, in this animal model of heart failure.