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Background Acute decompensated heart failure (ADHF) is the most common presenting phenotype of acute heart failure (AHF). The main goal of this article was to review the contemporary management strategies in these patients and to describe how future clinical trials may address unmet clinical needs. Areas of uncertainty The current pathophysiologic understanding of AHF is incomplete. The guideline recommendations for the management of ADHF are based only on algorithms provided by expert consensus guided by blood pressure and/or clinical signs of congestion or hypoperfusion. The lack of adequately conducted trials to address the unmet need for evidence therapy in AHF has not yet been surpassed, and at this time, there is no evidence-based strategy for targeted decongestive therapy to improve outcomes. The precise time point for initiation of guideline-directed medical therapies (GDMTs), as respect to moment of decompensation, is also unknown. Data sources The available data informing current management of patients with ADHF are based on randomized controlled trials, observational studies, and administrative databases. Therapeutic advances A major step-forward in the management of ADHF patients is recognizing congestion, either clinical or hemodynamic, as a major trigger for heart failure (HF) hospitalization and most important target for therapy. However, a strategy based exclusively on congestion is not sufficient, and at present, comprehensive assessment during hospitalization of cardiac and noncardiovascular substrate with identification of potential therapeutic targets represents "the corner-stone" of ADHF management. In the last years, substantial data have emerged to support the continuation of GDMTs during hospitalization for HF decompensation. Recently, several clinical trials raised hypothesis of "moving to the left" concept that argues for very early implementation of GDMTs as potential strategy to improve outcomes. Conclusions The management of ADHF is still based on expert consensus documents. Further research is required to identify novel therapeutic targets, to establish the precise time point to initiate GDMTs, and to identify patients at risk of recurrent hospitalization.

A young previously healthy patient presented with fever and altered mental status. Her evaluation would eventually reveal a profound hyponatremia in the setting of a viral meningoencephalitis. This case report reviews the evaluation of hyponatremia and treatment options for syndrome of inappropriate antidiuretic hormone hypersecretion, her ultimate diagnosis.

Treatment options for massive and submassive pulmonary embolus may include hemodynamic support, fibrinolysis, anticoagulation, and thrombectomy. Selection of the appropriate therapy requires scrutiny of the patient's hemodynamic status, preexisting conditions, risk of complications, and availability of services at the treatment center. This article illustrates a case of successful fibrinolysis and thrombectomy in a woman with massive pulmonary embolus. A discussion of the indications, benefits, and disadvantages of several pharmacologic, radiologic, and surgical interventions considered in pulmonary embolus will follow.

Anticoagulation has long complicated the care of hemorrhage in the emergency department and other acute care settings. With the advent of novel anticoagulants such as direct thrombin inhibitors and direct factor Xa inhibitors, the absence of any direct antidote for these medications presents new and difficult challenges in the management of hemorrhagic complications in these patients. We present 2 cases of patients with hemorrhagic complications taking novel oral anticoagulants, their management, and outcomes.

Background Dyspnea is a key target in both clinical management and clinical trials of acute heart failure syndromes and its relief important to patients, clinicians, investigators, and regulatory approval agencies. Despite its importance, the impact of early therapy on dyspnea is not well known. The severity of dyspnea may also be influenced by the conditions under which it is measured (ie, sitting up or lying down). URGENT Dyspnea (Ularitide Global Evaluation in Acute Decompensated Heart Failure) is a prospective multicenter study designed to address these issues. Methods and results Consenting adult patients with dyspnea secondary to acute heart failure syndromes are eligible. Patients must be interviewed within one hour of first physician evaluation, typically in an emergency department or acute care setting, with dyspnea assessed by the patient using both a 5-point Likert scale and 10-point visual analog scale in the sitting (60 degrees) and then supine (20 degrees ) position if symptomatically able. Improvement of dyspnea by change in Likert and visual analog scale scores at 6 h is the primary endpoint. Conclusions Timing of dyspnea measurement and the conditions under which it is measured may influence dyspnea severity and this may have significant implications for future acute heart failure syndromes clinical trial design that target dyspnea.

Nitrovasodilators (NVs) are commonly recommended for the treatment of acute heart failure (AHF); however, registries suggest their use is not common. The objectives of this study were to determine patient characteristics associated with NV use and to explore the association between NV use and outcomes [length of stay (LoS) and inpatient mortality] in patients with AHF. A survey of US physicians (n = 426) who treat at least 5 AHF patients per month with NV provided a patient sample (n = 812 treated with NV and n = 322 not-NV) derived from chart review. Factors associated with NV use as well as patient characteristics and outcomes associated with NV use were explored using bivariate analysis, logistic regression, and negative binomial regression as appropriate. NV-treated patients were more likely to be female, have a higher systolic blood pressure, higher B-type natriuretic peptide and troponin, and stay in the intensive care unit while hospitalized, but less likely to be hyponatremic or hospitalized once previously. Overall, average LoS was 5.10 days (SD = 4.52) with 5.21 days (SD = 0.15) for the NV group and 4.94 days (SD = 0.31) for the non-NV group. The overall inpatient mortality rate was 2.1%. Among physicians who frequently use NV to treat AHF patients, there are distinct patient characteristics between NV treated and nontreated patients, suggesting a phenotype-driven approach. However, no differences in LoS or mortality were observed.

BACKGROUND Current inotropes have inodilator properties and, although are frequently used in acute heart failure syndromes, do not improve outcomes, likely from reduction in systolic blood pressure and increasing in arrhythmias, causing worsened myocardial ischemia and end-organ damage. Istaroxime is a novel agent that, in animal models, has both inotropic (inhibition of the Na/K ATPase channel) and lusitropic (stimulation of sarcoplasmic reticulum calcium ATPase activity) effects. HORIZON-HF is designed to test the hypothesis that istaroxime is effective in improving central hemodynamics and left ventricular (LV) function, without lowering systolic blood pressure, increasing heart rate, and worsening renal function or myocardial necrosis. METHODS AND RESULTS This was a phase 2, randomized, double-blind, placebo-controlled, multicenter dose escalation exploratory study comparing 3 different doses of istaroxime to placebo in patients with LV systolic dysfunction (LV ejection fraction