Congestive Heart Failure

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57 Congestive Heart Failure

Epidemiology

With the aging of the U.S. population and improved survival after myocardial infarction, the prevalence of heart failure is on the rise.1 At the same time, advances in medical therapy are allowing patients with heart failure to live longer. In 2008, 5.7 million Americans were estimated to have heart failure, with approximately 670,000 new cases diagnosed that year. Heart failure contributes to nearly 300,000 deaths per year, and costs associated with the treatment of heart failure exceed $30 billion annually. Heart failure accounts for nearly 1 million inpatient admissions per year and represents the primary reason for hospitalization in the growing elderly population. Approximately four of every five patients hospitalized for heart failure initially come to the emergency department (ED) for treatment.

Evidence-based literature for ED management of heart failure lags behind that of other emergency conditions, such as acute coronary syndrome and stroke. The number of large, randomized controlled clinical trials is small, and most practice guidelines, such as those from the Heart Failure Society of America and the European Society of Cardiology, rely heavily on consensus statements.2,3 A recent American Heart Association scientific statement highlighted the significant gaps in knowledge and the lack of evidence-based approaches to the management of heart failure in the ED.4 In contrast, data from the Acute Decompensated Heart Failure National Registry (ADHERE) and the Acute Heart Failure Global Survey of Standard Treatment (ALARM-HF) registry have provided important insight into the clinical characteristics and actual patterns of care of these patients.5,6

In addition to the paucity of controlled clinical trial data, there remains confusion about terminology. Heart failure refers to the clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood. Causes of chronic heart failure are numerous and diverse (Box 57.1), but in the United States the majority of cases arise as a consequence of coronary artery disease and long-standing hypertension. The term acute heart failure is reserved for the presence of acute signs and symptoms of heart failure in an individual without previously known structural or functional cardiac disease. Examples of acute heart failure are massive ST-segment elevation myocardial infarction, acute papillary muscle rupture, and fulminant myocarditis. Much more commonly, a patient comes to the ED with worsening symptoms of known chronic heart failure, in common parlance a “heart failure exacerbation.” The term acute decompensated heart failure (ADHF) has been adopted to describe this phenomenon, whereby a patient with an established diagnosis of heart failure experiences increasing signs and symptoms of the disease after a period of relative stability.

Pathophysiology

In patients with chronic heart failure, inadequacy of cardiac function sets in motion a common set of compensatory mechanisms based on the Frank-Starling relationship and characterized by elevated sympathetic tone, fluid and salt retention, and ventricular remodeling. These adaptations can allow heart failure to remain stable (or “compensated”) for a time but also provide the final common pathway for decompensation—a downward spiral that can accelerate in response to a particular precipitant or stress (Fig. 57.1). High circulating levels of aldosterone, vasopressin, epinephrine, and norepinephrine can become maladaptive when tachycardia and vasoconstriction compromise intrinsic left ventricular (LV) performance and worsen myocardial oxygen balance. Deteriorating LV function can result in further neurohormonal activation and self-perpetuation of this adverse cycle. Acute decompensation can develop over a period of minutes, hours, or days and can range in severity from mild symptoms of volume overload or decreased cardiac output to frank pulmonary edema or cardiogenic shock.

Although ADHF represents a final common pathway, it is generally triggered by one or more specific precipitants (Box 57.2). Noncompliance with medications or dietary restrictions and myocardial ischemia are believed to be the most common causes of clinical cardiac decompensation. Other cardiovascular precipitants are arrhythmia (atrial fibrillation in particular), acute valvular dysfunction, and hypertensive crisis, but ADHF can also arise as a consequence of noncardiac conditions such as infections, anemia, alcohol withdrawal, uncontrolled diabetes, and thyroid disease.

Presenting Signs and Symptoms

The heterogeneity of the signs and symptoms in patients with ADHF reflects, to some extent, the relative contributions of volume overload, acute diastolic dysfunction, and low cardiac output (Table 57.1). Volume overload, which usually occurs in the setting of medication noncompliance or dietary indiscretion (or both), is classically associated with gradually worsening congestive symptoms. Acute diastolic dysfunction can occur in the setting of myocardial ischemia, tachyarrhythmia, or uncontrolled hypertension and is typically manifested as flash pulmonary edema. Nearly half of all patients admitted to the hospital for ADHF have mild or no impairment in systolic function.5 Overt manifestations of low cardiac output (i.e., hypoperfusion) are not generally seen except in patients with advanced LV dysfunction.

Most patients with ADHF have some degree of dyspnea. However, ADHF can closely mimic many other cardiac, respiratory, and systemic diseases. Historical features such as a history of orthopnea, paroxysmal nocturnal dyspnea, or peripheral edema make the diagnosis of ADHF more likely. The most valuable single piece of historical information to elicit from patients is a previous history of heart failure, myocardial infarction, or coronary artery disease. For example, patients evaluated in the ED because of acute dyspnea are approximately six times more likely to have ADHF if they have previously experienced heart failure (Table 57.2).7

Older patients may lack the typical signs and symptoms of heart failure because they are obscured by the aging process itself or by the presence of coexisting medical conditions. Nonspecific symptoms such as weakness, lethargy, fatigue, anorexia, and light-headedness may actually be manifestations of decreased cardiac output. Abdominal or epigastric discomfort can be a manifestation of low output or, more commonly, hepatic congestion.

Vital signs provide a sense of the severity of illness and can suggest etiologic factors for decompensation. Hyperthermia or hypothermia may indicate sepsis or thyroid disease. In the absence of rate-controlling pharmacologic agents, tachycardia is nearly universal in patients with decompensated heart failure. Bradycardia should raise concern for high-degree atrioventricular block, hyperkalemia, drug toxicity (digoxin, calcium channel blocker, beta-blocker), or severe hypoxia. Hypertension is commonly seen in patients with both systolic and diastolic dysfunction. Hypotension may represent baseline blood pressure (BP) in patients with end-stage cardiomyopathy but otherwise raises concern for shock, whether cardiogenic or otherwise.

The diagnostic utility of the physical examination has been well studied in the setting of chronic heart failure but less so for ADHF. It should be recognized that in ADHF, physical findings may be misleading because of the rapidly evolving clinical situation. Generally speaking, jugular venous distention, abdominojugular reflux, pedal edema, and an audible third heart sound are specific but insensitive indicators of heart failure, whereas the presence of pulmonary rales has only moderate specificity for heart failure (see Table 57.2).7

Differential Diagnosis and Medical Decision Making

The differential diagnosis in patients with acute respiratory distress is broad and includes ADHF, asthma, chronic obstructive pulmonary disease (COPD), pneumonia, pulmonary embolism, and multiple systemic diseases, including sepsis.

Even before patients reach the hospital, ADHF is associated with significant morbidity and mortality, including malignant arrhythmias and prehospital cardiac arrest. With few exceptions, the safety and efficacy of prehospital interventions have been poorly studied. Prehospital therapy for decompensated heart failure should be undertaken with caution in light of the relatively high number of inaccurate diagnoses made in the field. In as many as 50% of patients with assumed heart-associated respiratory distress, a different condition is diagnosed once they arrive at the hospital. Despite these concerns, evidence suggests that prehospital therapy for presumed heart failure can prevent serious complications and improve survival, particularly for critically ill patients. For example, prehospital use of continuous positive airway pressure (CPAP) in patients with acute pulmonary edema may avert the need for endotracheal intubation.8

Nitroglycerin appears to be the safest and most effective of the prehospital medications used for presumed pulmonary edema.9 The role of other medications for heart failure in the prehospital setting is less clear. Early administration of furosemide appears to have very little benefit and may result in short-term complications. Prehospital use of morphine sulfate for presumed pulmonary edema has been associated with a higher rate of endotracheal intubation, particularly in patients whose condition turns out to have been misdiagnosed in the field.

Diagnostic Studies

B-Type Natriuretic Peptide and NT-Probnp

B-type natriuretic peptide (BNP) is a counterregulatory hormone produced by cardiac myocytes in response to increased end-diastolic pressure and volume, as occurs in the setting of heart failure. ProBNP is released into the circulation and cleaved into biologically active BNP and an inactive N-terminal fragment, NT-proBNP, which has a half-life three to six times that of BNP. Plasma levels of BNP and NT-proBNP correlate with the degree of LV overload, severity of clinical heart failure, and both short- and long-term cardiovascular mortality.

Plasma levels of BNP and NT-proBNP have been shown to be useful in distinguishing between cardiac and noncardiac causes of dyspnea.10,11 Acutely dyspneic patients with plasma BNP levels lower than 100 pg/mL or NT-proBNP levels lower than 300 pg/mL are very unlikely to have ADHF (90% to 99% sensitivity), whereas those with BNP levels higher than 500 pg/mL or NT-proBNP levels higher than 1000 pg/mL are very likely to have ADHF (87% to 95% specificity). Intermediate levels must be interpreted in the clinical context (Fig. 57.2).

Interpretation of BNP levels must take into account baseline LV dysfunction and other known or suspected conditions associated with left or right ventricular pressure overload that may result in elevations in BNP. Patients with advanced age or renal insufficiency tend to have higher BNP and NT-proBNP levels, whereas those with a high body mass index tend to have lower levels. Although BNP and NT-proBNP measurements retain discriminatory power in these subpopulations, the optimal cutoff points for diagnosing ADHF may vary. The duration of symptoms also plays a role; for example, in the setting of acute pulmonary edema, these levels may not yet be elevated.

In general, emergency physicians (EPs) are about 80% accurate in distinguishing between cardiac and noncardiac causes of dyspnea on clinical grounds. Supplementing clinical acumen with routine BNP or NT-proBNP measurement does increase diagnostic accuracy overall, but as demonstrated in the Breathing Not Properly Multinational Study, the improvement is rather marginal.12 For example, in clear-cut cases, very high or very low values are unlikely to have an effect on diagnosis, whereas in less clear-cut cases, intermediate results are more likely.

BNP and NT-proBNP levels also carry modest prognostic information.13 Although levels at admission correlate only modestly with short-term outcomes, discharge levels are strong independent predictors of death or readmission.

Treatment

Priorities of Treatment

All patients with ADHF who are in respiratory distress should receive supplemental oxygen and be positioned upright, if possible, to improve respiratory dynamics and maximize oxygen delivery to vital organs. Practice guidelines recommend the early application of monitors, such as pulse oximetry, noninvasive BP, and continuous cardiac monitoring, to provide early warning of further decompensation.

Although most patients in respiratory distress can be managed with supplemental oxygen and noninvasive ventilatory support (see the next section), the presence of agonal respirations or profoundly depressed mental status mandates endotracheal intubation. In general, airway management should be accomplished with rapid-sequence intubation because prolonged attempts at intubation risk worsening hypoxia, further cardiac decompensation, and cardiopulmonary arrest. Keeping the patient in an upright position as long as possible before intubation may assist in maximizing preoxygenation. Most induction agents (thiopental, fentanyl, and midazolam) are associated with a significant risk for hypotension in patients with ADHF, whereas induction with etomidate is generally considered safe.

Noninvasive Respiratory Support

For patients with respiratory distress in whom intubation is not immediately required, noninvasive respiratory support via CPAP or bilevel positive airway pressure (BiPAP) should be instituted (Fig. 57.3). Although the decision to initiate noninvasive respiratory support may depend on a variety of factors, the presumption is that the earlier therapy is instituted, the greater the likelihood of averting intubation. Success also depends on appropriate patient selection. Patients with unstable cardiac rhythms or cardiogenic shock are generally believed to not be candidates for a noninvasive approach. Likewise, in the setting of severe myocardial ischemia or infarction, full ventilatory support may be preferable to decrease myocardial oxygen demand.

CPAP improves lung mechanics by recruiting atelectatic alveoli, improving pulmonary compliance, and reducing the work of breathing. At the same time, particularly in patients with heart failure, CPAP improves hemodynamics by reducing preload and afterload, thereby enhancing LV performance. Pooled data from several randomized, controlled clinical trials suggest that the use of CPAP (at 5 to 10 mm Hg) in patients with respiratory distress caused by ADHF reduces the frequency of endotracheal intubation and may be associated with lower mortality.14

BiPAP adds to the physiologic advantages of CPAP during expiration by providing differential positive pressure during inspiration, thereby providing direct assistance with ventilation. However, at present, little evidence suggests an advantage of BiPAP over CPAP in patients with ADHF and pure hypoxemic respiratory failure.

In patients with progressive respiratory failure despite noninvasive support, endotracheal intubation and mechanical ventilation should be instituted.

Pharmacologic Therapy

The twin objectives of pharmacologic therapy for ADHF are relief of pulmonary congestion and improvement in systemic tissue perfusion. Strategies to achieve these goals involve reducing preload and enhancing LV function while aiming to maintain or even improve myocardial oxygen balance (Table 57.3).

Diuretics

Diuretics constitute the mainstay of therapy for patients with volume overload. Although their use is widely recommended as initial therapy for most patients with ADHF, it should be noted that until very recently this practice had not been evaluated in any large, prospective trial. Evidence from in vitro and in vivo experiments suggests that the direct vascular effects of diuretics may also contribute to their mechanism of action. However, studies comparing the acute effects of diuretics and nitrates have tended to emphasize the more favorable overall hemodynamic effects of the latter group (see the next section).

Depending on a patient’s clinical condition and previous use of diuretics, an initial intravenous (IV) dose of furosemide, 20 to 200 mg, is typically administered. For patients already receiving diuretic therapy, a common strategy is to begin with the usual daily dose given as an IV bolus. A recently published multicenter, prospective, double-blind, randomized trial comparing a strategy of low-dose furosemide (equivalent to the patient’s previous oral dose) versus high-dose furosemide (2.5 times the previous oral dose) in 308 patients with ADHF found no significant differences in patients’ global assessment of symptoms or in the change in renal function over the first 72 hours.15 A high-dose strategy was associated with greater diuresis, but median length of hospital stay was not significantly different. In the same trial, patients randomized to bolus IV therapy (every 12 hours) or the same dose of furosemide delivered via continuous IV infusion had no significant difference in outcome.

It is important to recognize that not all patients with ADHF are substantially volume-overloaded. For example, patients with acute diastolic dysfunction may benefit more from redistribution of circulating volume (e.g., with a vasodilator) than from diuresis per se. The indiscriminate use of diuretics carries the risk for overdiuresis, with detrimental effects on systemic perfusion in general and renal function in particular.

Although not all patients with ADHF require bladder catheterization, monitoring of urinary output is important in any patient in whom diuresis is a chosen as a treatment strategy.

Nitrates

Nitrates are recommended for the treatment of ADHF, whether of ischemic or nonischemic origin. At low doses, nitroglycerin induces venodilation (preload reduction); at higher doses, nitroglycerin also causes arterial dilation (afterload reduction). Significantly, in patients with severe underlying LV dysfunction, afterload reduction appears to predominate over preload reduction, even with moderate doses of nitroglycerin.

Nitrates have been shown to be both safe and effective for the treatment of ADHF, particularly in the context of acute pulmonary edema.16 When compared with placebo therapy in the Vasodilation in the Management of Acute Congestive Heart Failure (VMAC) trial, IV nitroglycerin resulted in better dyspnea scores, but the study was not powered to demonstrate differences in morbidity or mortality.17

Single doses of sublingual nitroglycerin (0.4 mg) can be given repeatedly every 5 to 10 minutes to provide adequate BP. In the hospital setting, however, continuous IV administration of nitroglycerin is more convenient and allows titration to specific clinical or hemodynamic end points (typically starting at 10 to 20 mcg/min and ranging up to 200 mcg/min). The hemodynamic effects of transdermal nitroglycerin are comparable with those of IV nitroglycerin, but this route of administration is less amenable to titration and may be less effective in patients with poor skin perfusion.

The hypotension induced by standard nitrate therapy is generally mild and transient. Severe or persistent hypotension should raise suspicion for hypovolemia, stenotic valvular disease such as aortic stenosis, cardiac tamponade, right ventricular infarction, or recent use of sildenafil (Viagra). If these conditions are known or suspected, nitrates should be avoided or used with extreme caution. Nitrate therapy may not be particularly effective in patients with massive peripheral edema. In such cases, aggressive diuretic therapy is more likely to be of benefit.

Sodium nitroprusside is recommended for patients with marked systemic hypertension, severe mitral or aortic valvular regurgitation, or pulmonary edema not responsive to standard nitrate therapy. Nitroprusside profoundly dilates resistance vessels and thereby rapidly reduces BP and afterload. Typically, nitroprusside is started at a dose of 0.1 to 0.3 mcg/kg/min, and the dose is increased as needed to improve clinical and hemodynamic status while maintaining systolic BP above 90 mm Hg or mean arterial pressure above 65 mm Hg. In patients with renal insufficiency, long-term use of nitroprusside carries the potential for cyanide toxicity as metabolites of the agent accumulate.

Special Circumstances

Cardiogenic Shock

Heart failure with cardiogenic shock can be the initial manifestation of acute ST-segment elevation myocardial infarction. Although mortality remains high in this setting, referral for emergency cardiac catheterization and revascularization is of proven benefit. Noncardiac causes of shock, such as hypovolemia, sepsis, poisoning, and massive pulmonary embolism, must also be considered.

Aside from addressing reversible causes of shock, the overarching goal in treating patients with cardiogenic shock should be to restore and maintain perfusion of vital organs. Patients who are initially seen in shock with normal BP or only mild hypotension often have a favorable response to dobutamine (starting at 2 to 3 mcg/kg/min). When compared with dopamine, dobutamine is associated with a lower incidence of arrhythmias, less peripheral vasoconstriction, and more consistent reduction in LV filling pressure for a comparable rise in cardiac output. Dopamine is required for patients who have severe hypotension (systolic BP of approximately 70 to 80 mm Hg) in the presence of volume overload or after bolus administration of saline. At moderate doses (4 to 5 mcg/kg/min), dopamine improves cardiac output without causing excessive systemic vasoconstriction. If the patient can be stabilized with dopamine, dobutamine can then be added and the dose of dopamine lowered, with the goal of reducing myocardial oxygen demand. In extreme cases, norepinephrine can be added to increase systolic pressure to acceptable levels (≈80 mm Hg). However, because of the adverse effects on renal and mesenteric perfusion, use of high-dose dopamine or norepinephrine should be considered only as a temporizing measure until definitive therapy can be substituted.

It is important for the EP to distinguish patients with acute cardiogenic shock from those with low BP or other signs of systemic hypoperfusion in the setting of preexisting severe or end-stage systolic heart failure. Assessment and treatment of these patients can be extremely challenging, and optimal management may require the involvement of a heart failure specialist. Attempts to aggressively treat these patients can lead to rapid decompensation. Frequently, the key to management is identifying the cause of the decompensation.

Atrial Fibrillation

Atrial fibrillation is seen in approximately one third of patients with ADHF. Although loss of synchronized atrial contractions is of minimal hemodynamic significance in patients with normal ventricular function, in those who have abnormal LV systolic or diastolic function, loss of the atrial kick can have profound consequences. This is particularly evident when atrial fibrillation is accompanied by a rapid ventricular response, thereby reducing filling time.

When assessing a patient with rapid atrial fibrillation and ADHF, it is often difficult to attribute cause and effect. New-onset rapid atrial fibrillation may be the precipitant of ADHF, but more commonly, rapid atrial fibrillation is a response to worsening heart failure (e.g., via neurohormonal activation). This distinction can sometimes be difficult to make clinically, but regardless, attention must be paid, to some degree, to managing both conditions.

Management of atrial fibrillation in the context of ADHF should focus on treating the underlying precipitants of decompensation (e.g. volume overload) while also controlling the ventricular rate. However, caution should be exercised in the use of a beta-blocker or calcium channel blocker for rate control because of the potential negative inotropic effects. Digoxin, diltiazem, and amiodarone are considered acceptable agents for rate control, even in patients with LV systolic dysfunction. Cardioversion, whether electrical or chemical, is a reasonable treatment alternative for truly unstable atrial fibrillation, but sinus rhythm may not be achieved or maintained if the underlying heart failure is not addressed.

Follow-Up and Next Steps in Care

The vast majority of patients with ADHF evaluated in the ED are admitted to the hospital.5 Discharge from the ED without adequate treatment may be associated with recurrent visits and short-term morbidity and mortality. ADHF is often a dynamic entity: one patient may appear dramatically ill at initial evaluation but respond rapidly to treatment, whereas another patient may experience serious complications after a period of apparent stability. For any individual patient, identifying and addressing the precipitant of the decompensation is critical to making the correct disposition.

The Heart Failure Society of America has established criteria for discharging patients with heart failure from the ED (Box 57.3). However, these guidelines have not been prospectively studied. It should be noted that previously published criteria from the U.S. Agency for Health Care Policy and Research failed to account for more than 30% of 30-day mortality.24 Thus, although published guidelines can assist with triage, the significant rate of morbidity mandates that clinical judgment be incorporated into the decision-making process.

For patients with ADHF admitted to the hospital, inpatient mortality is approximately 4%, and the median length of stay exceeds 4 days.5 In those admitted with advanced stages of heart failure, inpatient mortality approaches 10%. Clinical correlates of major complications or death during hospitalization include hypotension; tachypnea; ECG abnormalities; hyponatremia; renal insufficiency; elevations in troponin, BNP, and NT-proBNP; and poor initial diuresis. However, even patients without any of these risk factors have measurable rates of in-hospital morbidity and mortality. A risk stratification tool derived from the ADHERE registry has been developed to help clinicians determine the risk for mortality in patients with ADHF (Fig. 57.4).25

For a patient discharged home from the ED, consultation with the patient’s primary care physician or cardiologist is important. For example, it is likely that the patient’s outpatient medication regimen will require adjustment to prevent a return to the ED. In some studies, intensive outpatient follow-up has been shown to be successful in preventing recurrent ED visits and hospitalizations.

References

1 Roger VL, Turner MB, on behalf of the American Heart Association Heart Disease and Stroke Statistics Writing Group. Heart disease and stroke statistics—2011 update: a report from the American Heart Association. Circulation. 2011;123:e18–e209.

2 Heart Failure Society of America. Executive summary: HFSA 2010 comprehensive heart failure practice guideline. J Card Fail. 2010;16:475–539.

3 The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008. Eur Heart J. 2008;29:2388–2442.

4 Weintraub NL, Collins SP, Pang PS, et al. Acute heart failure syndromes: emergency department presentation, treatment, and disposition: current approaches and future aims: a scientific statement from the American Heart Association. Circulation. 2010;122:1975–1996.

5 Adams KF, Jr., Fonarrow GC, Emerman CL, et al. Characteristics and outcomes of patients hospitalized for heart failure in the United States: rationale, design, and preliminary observations from the first 100,000 cases in the Acute Decompensated Heart Failure National Registry (ADHERE). Am Heart J. 2005;149:209–216.

6 Follath F, Yilmaz MB, Delgado JF, et al. Clinical presentation, management and outcomes in the Acute Heart Failure Global Survey of Standard Treatment (ALARM-HF). Intensive Care Med. 2011;37:619–626.

7 Wang CS, FitzGerald JM, Schulzer M, et al. Does this dyspneic patient in the emergency department have congestive heart failure? JAMA. 2005;294:1944–1956.

8 Hubble MW, Richards ME, Jarvis R, et al. Effectiveness of prehospital continuous positive airway pressure in the management of acute pulmonary edema. Prehosp Emerg Care. 2006;10:430–439.

9 Hoffman JR, Reynolds S. Comparison of nitroglycerin, morphine and furosemide in treatment of presumed pre-hospital pulmonary edema. Chest. 1987;92:586–593.

10 Maisel AS, Krishnaswamy P, Nowak RM, et al. Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J Med. 2002;347:161–167.

11 Januzzi JL, Jr., Camargo CA, Anwaruddin S, et al. The N-terminal Pro-BNP Investigation of Dyspnea in the Emergency department (PRIDE) study. Am J Cardiol. 2005;95:948–954.

12 McCullough PA, Nowak RM, McCord J, et al. B-type natriuretic peptide and clinical judgment in emergency diagnosis of heart failure: analysis from Breathing Not Properly (BNP) Multinational Study. Circulation. 2002;106:416–422.

13 Maisel A, Hollander JE, Guss D, et al. Primary results of the Rapid Emergency Department Heart Failure Outpatient Trial (REDHOT): a multicenter study of B-type natriuretic peptide levels, emergency department decision making, and outcomes in patients presenting with shortness of breath. J Am Coll Cardiol. 2004;44:1328–1333.

14 Vital FM, Saconato H, Ladeira MT, et al. Non-invasive positive pressure ventilation (CPAP or bilevel NPPV) for cardiogenic pulmonary edema. Cochrane Database Syst Rev. 3, 2008. CD005351

15 Felker GM, Lee KL, Bull DA, et al. Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med. 2011;364:797–805.

16 Cotter G, Metzkor E, Kaluski E, et al. Randomised trial of high-dose isosorbide dinitrate plus low-dose furosemide versus high dose furosemide plus low-dose isosorbide dinitrate in severe pulmonary edema. Lancet. 1998;351:389–393.

17 Publication Committee for the VMAC Investigators (Vasodilatation in the Management of Acute CHF). Intravenous nesiritide vs nitroglycerin for treatment of decompensated congestive heart failure: a randomized controlled trial. JAMA. 2002;287:1531–1540.

18 Sackner-Bernstein JD, Kowalski M, Fox M, et al. Short-term risk of death after treatment with nesiritide for decompensated heart failure: a pooled analysis of randomized controlled trials. JAMA. 2005;293:1900–1905.

19 Sackner-Bernstein JD, Skopicki HA, Aaronson KD. Risk of worsening renal function with nesiritide in patients with acutely decompensated heart failure. Circulation. 2005;111:1487–1491.

20 Hernandez AF. Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure Trial (ASCEND-HF)—nesiritide or placebo for improved symptoms and outcomes in acute decompensated HF. Chicago: American Heart Association 2010 Scientific Sessions; 2010.

21 Cuffe MS, Califf RM, Adams KF, et al. Short-term intravenous milrinone for acute exacerbation of chronic heart failure: a randomized controlled trial. JAMA. 2002;287:1541–1547.

22 Gheorghiade M, Konstam MA, Burnett JC, Jr., et al. Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heart failure: the EVEREST Clinical Status Trials. JAMA. 2007;297:1332–1343.

23 Costanzo MR, Guglin ME, Saltzberg MT, et al. UNLOAD Trial Investigators: ultrafiltration versus intravenous diuretics for patients hospitalized for acute decompensated heart failure. J Am Coll Cardiol. 2007;49:675–683.

24 Graff L, Orledge J, Radford MJ, et al. Correlation of the Agency for Health Care Policy and Research congestive heart failure admission guideline with mortality: peer review organization voluntary hospital association initiative to decrease events (PROVIDE) for congestive heart failure. Ann Emerg Med. 1999;34:429–437.

25 Fonarow GC, Adams KF, Jr., Abraham WT, et al. Risk stratification for in-hospital mortality in acutely decompensated heart failure: classification and regression tree analysis. JAMA. 2005;293:572–580.

26 Fermann GJ, Collins SP. Observation units in the management of acute heart failure syndromes. Curr Heart Fail Rep. 2010;7:125–133.