Drug Therapy for Acute Heart Failure

University Heart Journal, 2012

Acute heart failure is a major health problem responsible for several million hospitalizations worldwide each year. Standard therapy has not changed for long time and includes diuretics and variable use of vasodilators or inotropes. Recently Nesiritide and Levosimendan are two drugs for the treatment of acute heart failure which have been approved by the Food and Drug Administration (FDA) and European Medicines Agency (EMEA), respectively. There was little concern that Nesiritide can worsen the renal failure but recent trials had abolished this concern. DOI: http://dx.doi.org/10.3329/uhj.v7i1.10208 UHJ 2011; 7(1): 35-38

Heart Failure Reviews, 2009

Although we have recently witnessed substantial progress in management and outcome of patients with chronic heart failure, acute heart failure (AHF) management and outcome have not changed over almost a generation. Vasodilators are one of the cornerstones of AHF management; however, to a large extent, none of those currently used has been examined by large, placebocontrolled, non-hemodynamic monitored, prospective randomized studies powered to assess the effects on outcomes, in addition to symptoms. In this article, we will discuss the role of vasodilators in AHF trying to point out which are the potentially best indications to their administration and which are the pitfalls which may be associated with their use. Unfortunately, most of this discussion is only partially evidence based due to lack of appropriate clinical trials. In general, we believe that vasodilators should be administered early to AHF patients with normal or high blood pressure (BP) at presentation. They should not be administered to patients with low BP since they may cause hypotension and hypoperfusion of vital organs, leading to renal and/or myocardial damage which may further worsen patients' outcome. It is not clear whether vasodilators have a role in either patients with borderline BP at presentation (i.e., low-normal) or beyond the first 1-2 days from presentation. Given the limitations of the currently available clinical trial data, we cannot recommend any specific agent as first line therapy, although nitrates in different formulations are still the most widely used in clinical practice.

European Heart Journal Supplements, 2016

The prevalence of heart failure (HF) continues to grow, in large part attributed to the aging population. Parallel to this trend is the increasing burden of hospitalization for worsening HF, which accounts for the majority of the very high societal burden of costs of care for these patients. These hospitalizations represent a change in the trajectory of the disease process and are associated with a significantly higher risk of adverse outcomes, a trend that has not changed over the past two decades. Although short-term readmissions are due to haemodynamic congestion, long-term prognosis and mortality are the result of the continuous deterioration of cardiac substrate, worsening of comorbidities, and progression of HF. Thus, when planning a new therapeutic intervention in acute HF, it is essential to have insight into the mechanism and temporal distribution of adverse outcomes. Furthermore, as acute HF patients die or are readmitted due to multiple reasons it is important to match the mechanism of action of the intervention to the mechanism of the adverse event. Despite many clinical trials to date in these patients, there currently is not a single agent that is known to improve post-discharge mortality risk in these patients. A variety of reasons have been offered to account for the lack of success in these clinical trials. A careful review of these previous experiences offers some significant insights into lessons learned and provides guidance for future novel intervention development for this growing patient population.

Research Reports in Clinical Cardiology, 2014

Acute heart failure (AHF) represents a major burden in developed countries. However, pharmacological approaches have remained almost the same for 30 years and are still based on consensus rather than evidence, given that no medical therapy has been shown to positively affect clinical outcomes. Current pharmacological approaches are still based on decongestion by using diuretics in almost all patients, plus either vasodilators or inotropic agents to improve hemodynamics according to perfusion status. The role of loop diuretics (furosemide) and nitrates (nitroglycerin and nitroprusside) is well established, but new agents such as vasopressin and adenosine antagonists, as well as nesiritide, have failed to show any additional value. In the presence of hypoperfusion, the use of inotropics must be considered despite the lack of benefit in terms of survival, and the use of phosphodiesterase inhibitors and levosimendan has not shown any significant advantages over catecholamines (dobutamine). AHF involves a wide spectrum of patients and syndromes, and this probably accounts for the failure of trials set up to evaluate new therapeutic approaches for improving outcomes: therapies need to be tailored to specific patients. At this time, serelaxin represents a promising new agent which has a multifaceted effect, including organ protection, and has shown encouraging results when tailored for a well defined population. In addition, the role of ularitide, a synthetic form of the natriuretic peptide urodilatin, and the new cardiac myosin activators, as a new class of inotropic agents, will be established in the near future by ongoing trials. Therefore, AHF continues to be an unsolved problem and, in light of the lessons learned, new pharmacological approaches should be tailored to well defined AHF populations, incorporating concepts such as "the sooner the better", "improve and stabilize", and "prevent organ damage", in order to be able to improve clinical outcomes, including both mortality and readmission rates.

Swiss Medical Weekly, 2010

The recent European Society of Cardiology (ESC) guidelines delineate the diagnosis and management of distinct categories of acute heart failure syndromes. However, physicians dealing with these patients may need guidance in choosing therapeutic alternatives as soon as the dyspneic patient arrives at the emergency department, until distinct categories of the ESC guidelines are identified. Hence, this manuscript summarizes practical recommendations for the very early management of patients with acute heart failure syndromes. The recommendations are based on a clinical classification system considering the initial systolic blood pressure and other symptoms. Early initiation of diagnostic and goal-directed treatment strategies are key factors in improving patient outcomes. Early and frequent reassessment is also imperative so that adjustments to the initial therapeutic approach can be made, as clinically indicated.

2010

The Keio Journal of Medicine, 1987

Digitalis glycosides have been used for more than 200 years to treat chronic congestive heart failure although they often fail to provide adequate support in a patient with a severely depressed heart at the dose that does not cause toxicity. Improvement of this class of drugs is not feasible because both the therapeutic and toxic actions are caused by the same mechanism, i.e., inhibition of the sarcolemmal sodium pump. Despite the initial optimism with "newer" positive inotropic drugs, they are not free from toxicity which is caused by Ca2+ overload or from their tendency to inhibit relaxation. Moreover, these drugs fail to reduce risk factors in patients with advanced heart failure. Mortality of these patients is reduced by vasodilator therapy combined with digitalis and a diuretic. This therapy reduces preload and afterload, and hence workload, in addition to increasing the force of myocardial contraction, and minimizes deficiencies of failing heart. In this regard, importance of nonpharmacologic therapies for re duction of cardiac workload should also be emphasized. All these treatments, however, are palliative. We know very little about the basic changes that lead to heart failure, and treatments to prevent those changes are presently un available.

BMJ, 1998

Heart failure represents a complex clinical syndrome characterised by abnormalities of left ventricular function and neurohormonal regulation, exercise intolerance, shortness of breath, fluid retention, and reduced longevity. 1 Despite improvements in treatment the prognosis for patients with heart failure remains poor: the risk of death annually is 5%-10% in patients with mild symptoms and 30%-40% in those with advanced disease. 2 3 This condition is also associated with major morbidity and healthcare expenditure, being responsible for about 5% of hospital admissions in the United Kingdom. This review deals only with pharmacological treatments in chronic heart failure. Non-pharmacological measures apply to all patients, whereas surgical and device treatments (many still experimental) apply only to specific patient subsets. Patients with clinical symptoms of heart failure but normal or near normal left ventricular systolic function often have impaired left ventricular diastolic function. This heterogeneous group has been generally excluded from heart failure trials. We do not discuss the treatment of diastolic left ventricular dysfunction or acute heart failure syndromes: more comprehensive reviews are available. 5 This review is based primarily on randomised clinical trials of drug treatments in chronic heart failure. We selected original articles from Medline (1966-99) published in quality journals using the keywords heart failure, congestive, therapy, and randomised controlled trials, and we studied meta-analyses and major reviews in heart failure.

European Heart Journal: Acute Cardiovascular Care, 2013

To examine the use of the treatments for acute heart failure (AHF) recommended by ESC guidelines in different clinical presentations and blood pressure groups. Methods: The use of intravenous diuretics, nitrates, opioids, inotropes, and vasopressors as well as non-invasive ventilation (NIV) was analysed in 620 patients hospitalized due to AHF. The relation between AHF therapies and clinical presentation, especially systolic blood pressure (SBP) on admission, was also assessed. Results: Overall, 76% of patients received i.v. furosemide, 42% nitrates, 29% opioids, 5% inotropes and 7% vasopressors, and 24% of patients were treated with NIV. Furosemide was the most common treatment in all clinical classes and irrespective of SBP on admission. Nitrates were given most often in pulmonary oedema and hypertensive AHF. Overall, only SBP differed significantly between patients with and without the studied treatments. SBP was higher in patients treated with nitrates than in those who were not (156 vs. 141 mmHg, p<0.001). Still, only one-third of patients presenting acute decompensated heart failure and SBP over 120 mmHg were given nitrates. Inotropes and vasopressors were given most frequently in cardiogenic shock and pulmonary oedema, and their use was inversely related to initial SBP (p<0.001). NIV was used only in half of the cardiogenic shock and pulmonary oedema patients. Conclusions: The management of AHF differs between ESC clinical classes and the use of i.v. vasoactive therapies is related to the initial SBP. However, there seems to be room for improvement in administration of vasodilators and NIV.

Heart Failure Reviews, 2009

Treatment with inotropic agents is one of the most controversial topics in heart failure. Initial enthusiasm, based on strong pathophysiological rationale and apparent empirical efficacy, has been progressively limited by results of controlled trials and registries showing poorer outcomes of the patients on inotropic therapy. The use of these agents remains, however, potentially indicated in a significant proportion of patients with low cardiac output, peripheral hypoperfusion and end-organ dysfunction caused by heart failure. Limitations of inotropic therapy seem to be mainly related to their mechanisms of action entailing arrhythmogenesis, peripheral vasodilation, myocardial ischemia and damage, and possibly due to their use in patients without a clear indication, rather than to the general principle of inotropic therapy itself. This review will discuss the characteristics of the patients with a potential indication for inotropic therapy, the main data from registries and controlled trials, the mechanism of the untoward effects of these agents on outcomes and, lastly, perspectives with new agents with novel mechanisms of action.