Nitrates as a Treatment of Acute Heart Failure.
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ABSTRACT:
SUBMITTER: Alzahri MS
PROVIDER: S-EPMC5490950 | biostudies-other | 2016 May
REPOSITORIES: biostudies-other
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Project description:The prevalence of heart failure (HF) is on the rise due to the aging of society. Furthermore, the continuous progress and widespread adoption of screening and diagnostic strategies have led to an increase in the detection rate of HF, effectively increasing the number of patients requiring monitoring and treatment. Because HF is associated with substantial rates of mortality and morbidity, as well as high socioeconomic burden, there is an increasing need for developing specific guidelines for HF management. The Korean guidelines for the diagnosis and management of chronic HF were introduced in March 2016. However, chronic and acute HF represent distinct disease entities. Here, we introduce the Korean guidelines for the management of acute HF with reduced or preserved ejection fraction. Part II of this guideline covers the treatment of acute HF.
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Project description:Acute heart failure (AHF) is a life-threatening emergency, which largely profits from early diagnosis and treatment. The prevalence of AHF is difficult to assess, estimates range between 1 and 12% in the general population. Despite recent therapeutic advances, in-hospital mortality is high with estimates varying from 4 and 18% in different registries. Due to large differences in AHF definitions and selection criteria AHF populations vary in their characteristics and outcomes. This is especially true for randomized clinical trials and the external validity of some of these trials is questionable. Additionally, the timing of data collection and/or initiation of new therapies vary with the setting of trials. The aim of this article is to call attention to the difference in AHF populations and to emphasize the need for research to clearly define these populations. AHF populations from registries and clinical trials are the basis for evidence-based management strategies. It is important that these populations represent the patients in whom these strategies will be applied in routine care.
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Project description:Acute heart failure (AHF) is a life-threatening medical condition, where urgent diagnostic and treatment methods are of key importance. However, there are few evidence-based treatment methods. Interestingly, despite relatively similar ways of management of AHF throughout the globe, mid-term outcome in East Asia, including South Korea is more favorable than in Europe. Yet, most of the treatment methods are symptomatic. The cornerstone of AHF management is identifying precipitating factors and specific phenotype. Multidisciplinary approach is important in AHF, which can be caused or aggravated by both cardiac and non-cardiac causes. The main pathophysiological mechanism in AHF is congestion, both systemic and inside the organs (lung, kidney, or liver). Cardiac output is often preserved in AHF except in a few cases of advanced heart failure. This paper provides guidance on AHF management in a time-based approach. Treatment strategies, criteria for triage, admission to hospital and discharge are described.
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Project description:Congestive heart failure (CHF) is one of the most common reasons for hospitalization in the United States. Despite multiple different beneficial medications for the treatment of chronic CHF, there are no therapies with a demonstrated mortality benefit in the treatment of acute decompensated heart failure. In fact, studies of inotropes used in this setting have demonstrated more harm than good. Arginine vasopressin has been shown to be up regulated in CHF. When bound to the V1a and/or V2 receptors, vasopressin causes vasoconstriction, left ventricular remodeling and free water reabsorption. Recently, two drugs have been approved for use that antagonize these receptors. Studies thus far have indicated that these medications, while effective at aquaresis (free water removal), are safe and not associated with increased morbidity such as renal failure and arrhythmias. Both conivaptan and tolvaptan have been approved for the treatment of euvolemic and hypervolemic hyponatremia. We review the results of these studies in patients with heart failure.
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Project description:Heart failure is one of the most common diseases of adults in Europe, with an overall prevalence of 1-2%. Among persons aged 60 and above, its prevalence is above 10% in men and 8% in women. Acute heart failure has a poor prognosis; it is associated with a high rate of rehospitalization and a 1-year mortality of 20-30%.This review is based on pertinent literature, including guidelines, retrieved by a selective search in PubMed.There are different types of acute heart failure; the basic diagnostic assessment is performed at once and consists of ECG, echocardiography, and the measurement of N-terminal pro-brain natriuretic peptide (NTproBNP) and troponin levels. The most common causes of decompensation are arrhythmia, valvular dysfunction, and acute cardiac ischemia, each of which accounts for 30% of cases. The potential indication for immediate revascularization should be carefully considered in cases where acute heart failure is due to coronary heart disease. The basic treatment of acute heart failure is symptomatic, with the administration of oxygen, diuretics, and vasodilators. Ino-tropic agents, vasopressors, and temporary mechanical support for the circulatory system are only used to treat cardiogenic shock.The treatment of acute heart failure is markedly less evidence-based than that of chronic heart failure. Newer treatment approaches that are intended to improve outcomes still need to be tested in multicenter trials.
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Project description:The nitroxyl (HNO) donor, Angeli's salt, exerts positive inotropic, lusitropic, and vasodilator effects in vivo that are cAMP independent. Its clinical usefulness is limited by chemical instability and cogeneration of nitrite which itself has vascular effects. Here, we report on effects of a novel, stable, pure HNO donor (CXL-1020) in isolated myoctyes and intact hearts in experimental models and in patients with heart failure (HF).CXL-1020 converts solely to HNO and inactive CXL-1051 with a t1/2 of 2 minutes. In adult mouse ventricular myocytes, it dose dependently increased sarcomere shortening by 75% to 210% (50-500 ?mol/L), with a ?30% rise in the peak Ca(2+) transient only at higher doses. Neither inhibition of protein kinase A nor soluble guanylate cyclase altered this contractile response. Unlike isoproterenol, CXL-1020 was equally effective in myocytes from normal or failing hearts. In anesthetized dogs with coronary microembolization-induced HF, CXL-1020 reduced left ventricular end-diastolic pressure and myocardial oxygen consumption while increasing ejection fraction from 27% to 40% and maximal ventricular power index by 42% (both P<0.05). In conscious dogs with tachypacing-induced HF, CXL-1020 increased contractility assessed by end-systolic elastance and provided venoarterial dilation. Heart rate was minimally altered. In patients with systolic HF, CXL-1020 reduced both left and right heart filling pressures and systemic vascular resistance, while increasing cardiac and stroke volume index. Heart rate was unchanged, and arterial pressure declined modestly.These data show the functional efficacy of a novel pure HNO donor to enhance myocardial function and present first-in-man evidence for its potential usefulness in HF.URL: http://www.clinicaltrials.gov. Unique identifiers: NCT01096043, NCT01092325.
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Project description:Congestion is a major reason for hospitalization in acute heart failure (HF). Therapeutic strategies to manage congestion include diuretics, vasodilators, ultrafiltration, vasopressin antagonists, mineralocorticoid receptor antagonists, and potentially also novel therapies such as gut sequesterants and serelaxin. Uncertainty exists with respect to the appropriate decongestion strategy for an individual patient. In this review, we summarize the benefit and risk profiles for these decongestion strategies and provide guidance on selecting an appropriate approach for different patients. An evidence-based initial approach to congestion management involves high-dose i.v. diuretics with addition of vasodilators for dyspnoea relief if blood pressure allows. To enhance diuresis or overcome diuretic resistance, options include dual nephron blockade with thiazide diuretics or natriuretic doses of mineralocorticoid receptor antagonists. Vasopressin antagonists may improve aquaresis and relieve dyspnoea. If diuretic strategies are unsuccessful, then ultrafiltration may be considered. Ultrafiltration should be used with caution in the setting of worsening renal function. This review is based on discussions among scientists, clinical trialists, and regulatory representatives at the 9th Global Cardio Vascular Clinical Trialists Forum in Paris, France, from 30 November to 1 December 2012.
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Project description:COPD is a common comorbidity in patients with heart failure, yet little is known about the impact of this condition in patients with acute decompensated heart failure (ADHF), especially from a more generalizable, community-based perspective. The primary objective of this study was to describe the in-hospital and postdischarge mortality and treatment of patients hospitalized with ADHF according to COPD status.The study population consisted of patients hospitalized with ADHF at all 11 medical centers in central Massachusetts during four study years: 1995, 2000, 2002, and 2004. Patients were followed through 2010 for determination of their vital status.Of the 9,748 patients hospitalized with ADHF during the years under study, 35.9% had a history of COPD. The average age of this population was 76.1 years, 43.9% were men, and 93.3% were white. At the time of hospital discharge, patients with COPD were less likely to have received evidence-based heart failure medications, including β-blockers and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, than patients without COPD. Multivariable, adjusted in-hospital death rates were similar for patients with and without COPD. However, among patients who survived to hospital discharge, patients with COPD had a significantly higher risk of dying at 1 year (adjusted relative risk [RR], 1.10; 95% CI, 1.06-1.14) and 5 years (adjusted RR, 1.40; 95% CI, 1.28-1.52) after hospital discharge than patients who were not previously diagnosed with COPD.COPD is a common comorbidity in patients hospitalized with ADHF and is associated with a worse long-term prognosis. Further research is required to understand the complex interactions of these diseases and ensure that patients with ADHF and COPD receive optimal treatment modalities.
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Project description:Over the last 50 years, clinical trials of novel interventions for acute heart failure (AHF) have, with few exceptions, been neutral or shown harm. We hypothesize that this might be related to a differential response to pharmacological therapy.We studied the magnitude of treatment effect of rolofylline across clinical characteristics and plasma biomarkers in 2033 AHF patients and derived a biomarker-based responder sum score model. Treatment response was survival from all-cause mortality through day 180.In the overall study population, rolofylline had no effect on mortality (HR 1.03, 95% CI 0.82-1.28, p = 0.808). We found no treatment interaction across clinical characteristics, but we found interactions between several biomarkers and rolofylline. The biomarker-based sum score model included TNF-R1?, ST2, WAP four-disulfide core domain protein HE4 (WAP-4C), and total cholesterol, and the score ranged between 0 and 4. In patients with score 4 (those with increased TNF-R1?, ST2, WAP-4C, and low total cholesterol), treatment with rolofylline was beneficial (HR 0.61, 95% CI 0.40-0.92, p = 0.019). In patients with score 0, treatment with rolofylline was harmful (HR 5.52, 95% CI 1.68-18.13, p = 0.005; treatment by score interaction p < 0.001). Internal validation estimated similar hazard ratio estimates (0 points: HR 5.56, 95% CI 5.27-7-5.87; 1 point: HR 1.31, 95% CI 1.25-1.33; 2 points: HR 0.75, 95% CI 0.74-0.76; 3 points: HR 1.13, 95% CI 1.11-1.15; 4 points, HR 0.61, 95% CI 0.61-0.62) compared to the original data.Biomarkers are superior to clinical characteristics to study treatment heterogeneity in acute heart failure.
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Project description:AimsInsufficient diuretic response frequently occurs in patients admitted for acute heart failure (HF) and is associated with worse clinical outcomes. Recent studies have shown that measuring natriuresis early after hospital admission could reliably identify patients with a poor diuretic response during hospitalization who might require enhanced diuretic treatment. This study will test the hypothesis that natriuresis-guided therapy in patients with acute HF improves natriuresis and clinical outcomes.MethodsThe Pragmatic Urinary Sodium-based treatment algoritHm in Acute Heart Failure (PUSH-AHF) is a pragmatic, single-centre, randomized, controlled, open-label study, aiming to recruit 310 acute HF patients requiring treatment with intravenous loop diuretics. Patients will be randomized to natriuresis-guided therapy or standard of care. Natriuresis will be determined at set time points after initiation of intravenous loop diuretics, and treatment will be adjusted based on the urinary sodium levels in the natriuresis-guided group using a pre-specified stepwise approach of increasing doses of loop diuretics and the initiation of combination diuretic therapy. The co-primary endpoint is 24-h urinary sodium excretion after start of loop diuretic therapy and a combined endpoint of all-cause mortality or first HF rehospitalization at 6 months. Secondary endpoints include 48- and 72-h sodium excretion, length of hospital stay, and percentage change in N-terminal pro brain natriuretic peptide at 48 and 72 h.ConclusionThe PUSH-AHF study will investigate whether natriuresis-guided therapy, using a pre-specified stepwise diuretic treatment approach, improves natriuresis and clinical outcomes in patients with acute HF.
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