INTRODUCTION — Acute decompensated heart failure (ADHF) is a common and potentially fatal cause of acute respiratory distress. The clinical syndrome is characterized by the development of dyspnea, generally associated with rapid accumulation of fluid within the lung's interstitial and alveolar spaces, which is the result of acutely elevated cardiac filling pressures (cardiogenic pulmonary edema) . ADHF can also present as elevated left ventricular (LV) filling pressures and dyspnea without pulmonary edema.
ADHF is most commonly due to LV systolic or diastolic dysfunction, with or without additional cardiac pathology, such as coronary artery disease or valve abnormalities. However, a variety of conditions or events can cause cardiogenic pulmonary edema due to an elevated pulmonary capillary wedge pressure in the absence of heart disease, including primary fluid overload (eg, due to blood transfusion), severe hypertension (particularly renovascular hypertension), and severe renal disease.
In the large majority of patients who present with ADHF, acute or subacute decompensation is in the context of chronic HF with reduced ejection fraction (also known as systolic HF) or HF with preserved ejection fraction (also known as diastolic HF) and in many cases, there is a prior history of episodes of decompensation. In such patients, information regarding the precipitating factors, workup for HF, and the elements of successful therapy for prior episodes (eg, types and doses of diuretics used) can be of great value in approaching the current episode.
The components of therapy of ADHF in patients without acute myocardial infarction (MI) will be reviewed here. A table to assist with emergency management of ADHF is provided (table 1). General considerations for treatment of ADHF and the pathophysiology and evaluation of patients with ADHF are presented separately. (See "Treatment of acute decompensated heart failure: General considerations" and "Approach to diagnosis and evaluation of acute decompensated heart failure in adults".) (Related Pathway(s): Acute decompensated heart failure: Initial management of hypervolemic patients with adequate perfusion.)
Treatment of ADHF and cardiogenic shock in the setting of acute coronary syndrome and management of refractory HF (including inadequate response to diuretic therapy) are discussed separately. Management of right ventricular MI, which typically presents with hypotension and clear lungs, is also discussed separately. (See "Treatment of acute decompensated heart failure in acute coronary syndromes" and "Prognosis and treatment of cardiogenic shock complicating acute myocardial infarction" and "Management of refractory heart failure with reduced ejection fraction" and "Right ventricular myocardial infarction".)
Approach to general management — Patients presenting with acute dyspnea from ADHF should be rapidly assessed and stabilized. A table to assist with emergency management of ADHF is provided (table 1). The initial approach is similar in patients with ADHF whether caused by systolic or diastolic dysfunction. Initial measures include:
●Airway assessment and continuous pulse oximetry to assure adequate oxygenation and ventilation.
●Supplemental oxygen and ventilatory support (noninvasive ventilation [NIV] or intubation) as indicated.
●Vital signs assessment with attention to hypotension or hypertension.
●Continuous cardiac monitoring.
●Intravenous (IV) access.
●Prompt diuretic therapy.
●Early vasodilator therapy (for severe hypertension, acute mitral regurgitation, or acute aortic regurgitation); later vasodilator use for refractory cases is discussed below.
●Urine output monitoring (perhaps with urethral catheter placement).
Following airway and oxygenation assessment and management, initial therapy includes the initiation of treatments aimed at rapidly correcting hemodynamic and intravascular volume abnormalities. It is important to tailor the therapy to the individual patient. The mainstay of therapy in the acute setting is the use of diuretics to alleviate volume overload.
Early IV vasodilator therapy with an agent that lowers arterial tone (eg, nitroprusside) is suggested in selected patients with ADHF who require a rapid decrease in systemic vascular resistance and LV afterload (eg, those with severe hypertension, acute mitral regurgitation, or acute aortic regurgitation). Early use of a vasodilator that acts to lower venous tone (eg, nitroglycerin) is suggested when the initial response to diuretics is not sufficient to alleviate respiratory distress. The aggressiveness of diuretic and vasodilator therapy depends on the patient's hemodynamic and volume status. Patients with flash pulmonary edema due to hypertension, for instance, require aggressive vasodilatory therapy, as they often are not fluid overloaded. Patients with normotension and volume overload may be treated with diuretic therapy with or without vasodilator therapy.
Venous thromboembolism prophylaxis is indicated in patients hospitalized with acute HF. Sodium restriction is suggested in all patients with HF.
Vasopressin receptor antagonists are a rarely required option for patients with volume overload with severe hyponatremia (ie, serum sodium ≤120 mEq/L) despite fluid restriction. We suggest generally avoiding opiate therapy in patients with ADHF.
Supplemental oxygen and assisted ventilation — Supplemental oxygen therapy and assisted ventilation should be provided as needed to treat hypoxemia (SpO2 <90 percent). Oxygen is not recommended as routine therapy in patients without hypoxemia, as it may cause vasoconstriction and reduction in cardiac output .
For patients requiring supplemental oxygen, we suggest initial therapies in the following order:
●In general, a nonrebreather face mask with high-flow 100 percent O2 is used because the concentration of delivered oxygen is greater than with nasal cannula. However, patients who also have chronic obstructive pulmonary disease (COPD) may not require aggressive oxygen therapy, since the target O2 saturation in such patients is 88 to 92 percent. In patients with both acute HF and COPD, we aim for the upper end of that range. (See "COPD exacerbations: Management".)
●If respiratory distress, respiratory acidosis, and/or hypoxia persist on oxygen therapy, we recommend a trial of noninvasive ventilation (NIV) if emergent intubation is not indicated (algorithm 1), no contraindications to NIV exist (table 2), and personnel with experience in NIV are available.
This approach is supported by evidence from meta-analyses and randomized trials in patients with cardiogenic pulmonary edema, indicating that NIV decreases the need for intubation and improves respiratory parameters, such as dyspnea, hypercapnia, acidosis, and heart rate. NIV may be particularly beneficial in patients with hypercapnia. These issues and conflicting data on a possible impact on mortality are discussed in detail separately. (See "Noninvasive ventilation in adults with acute respiratory failure: Benefits and contraindications", section on 'Acute cardiogenic pulmonary edema (ACPE)'.)
●Patients with respiratory failure who fail to improve with NIV (within one-half to two hours) or do not tolerate or have contraindications to NIV (table 2) should be intubated for conventional mechanical ventilation. In such patients, positive end-expiratory pressure is often useful to improve oxygenation. (See "Overview of initiating invasive mechanical ventilation in adults in the intensive care unit" and "Positive end-expiratory pressure (PEEP)".)
Once initial therapy has begun, oxygen supplementation can be titrated in order to keep the patient comfortable and arterial oxygen saturation consistently above 90 percent.
Efficacy — Limited clinical trial data have shown a mortality benefit from diuretic therapy in patients with chronic HF (see "Use of diuretics in patients with heart failure", section on 'Efficacy and safety'). Although the safety and efficacy of diuretics to treat ADHF have not been established in randomized trials, extensive observational experience has demonstrated that they effectively relieve congestive symptoms  and are essential for the successful treatment of most patients with ADHF and volume overload.
Urgency — Patients with ADHF and evidence of volume overload, regardless of etiology, should be promptly treated with IV diuretics as part of their initial therapy [4-6]. As noted in the 2013 American College of Cardiology Foundation/American Heart Association (ACC/AHA) HF guidelines, patients admitted with significant fluid overload should receive diuretic therapy without delay in the emergency department or outpatient clinic, as early intervention may produce better outcomes .
The expeditious initiation of an effective IV loop diuretic regimen is important in controlling dyspnea and other symptoms related to fluid overload, and in addition, may improve in-hospital outcomes. A multicenter, prospective observational study of 1291 patients with ADHF treated with IV furosemide within 24 hours of their arrival in an emergency department found that early treatment (<60 minutes) was associated with a lower in-hospital mortality than later treatment (2.3 versus 6.0 percent) . Early treatment remained significantly associated with lower in-hospital mortality in multivariate analysis (odds ratio [OR] 0.39, 95% CI 0.20-0.76). As time to diuresis was delayed, the risk of mortality increased steeply during the first 100 minutes and then leveled off.
Rare exceptions in which some delay in diuresis may be required include patients with severe hypotension or cardiogenic shock. In such cases, the underlying cause for hemodynamic instability should be sought, and the patient may require hemodynamic and mechanical ventilatory support along with diuresis. Such patients may have inadequate LV filling pressures, and could be adversely affected by a diuresis. Patients with aortic stenosis with volume overload should be diuresed with caution.
Patients with ADHF are usually volume overloaded. Even in the less common situation in which cardiogenic pulmonary edema develops without significant volume overload (eg, with hypertensive emergency, acute aortic or mitral valvular insufficiency), fluid removal with IV diuretics can relieve symptoms and improve oxygenation. IV rather than oral administration is recommended because of greater and more consistent drug bioavailability.
Individualized dosing — Diuretic dosing should be individualized and titrated according to patient status and response. The approach to initial diuretic therapy in patients with ADHF and fluid overload varies according to whether or not the patient has received prior loop diuretic therapy:
●For patients who have not previously received loop diuretic therapy, the following are common initial IV doses of loop diuretics in patients with normal renal function:
•Furosemide – 20 to 40 mg IV
•Bumetanide – 1 mg IV
•Torsemide – 10 to 20 mg IV
If there is little or no response to the initial dose, the dose should be doubled at two-hour intervals as needed up to the maximum recommended doses. While patients with a relatively normal glomerular filtration rate (typically estimated from the serum creatinine concentration, although this method can be used only if kidney function is stable) can usually be diuresed with IV doses of 40 to 80 mg of furosemide, 20 to 40 mg of torsemide, or 1 to 2 mg of bumetanide, patients with renal insufficiency or severe HF may require higher maximum bolus doses of up to 160 to 200 mg of furosemide, 100 to 200 mg of torsemide, or 4 to 8 mg of bumetanide . (See "Causes and treatment of refractory edema in adults".)
●Patients treated with loop diuretics chronically may need a higher dose in the acute setting; the initial daily IV dose should be equal to or greater than (eg, 2.5 times) their maintenance total daily oral dose (eg, for a patient who had been taking 20 mg orally twice daily, an initial daily IV furosemide dose of 40 to 100 mg which could be administered as 20 mg to 50 mg IV boluses twice daily) and then adjusted depending upon the response. In the DOSE trial of IV furosemide in patients with ADHF, there was an almost significant trend toward greater improvement in patients’ global assessment of symptoms in the high-dose (total daily IV dose 2.5 times the patients’ prior total daily oral diuretic dose) group compared with the low-dose (equal to the prior total daily dose) group, as discussed below . Subsequent dose escalation and maximum doses are similar to those used in patients who are not already being treated with loop diuretics.
Bolus diuretic administration two or more times per day may be necessary. A continuous IV infusion is an alternative to IV bolus therapy, although data are limited . Use of a continuous IV infusion requires that the patient be responsive to IV bolus therapy, which results in higher initial plasma concentrations and therefore higher initial rates of urinary diuretic excretion than a continuous infusion. A continuous infusion should not be tried in patients who have not shown response to a maximum IV bolus dose. (See "Use of diuretics in patients with heart failure" and "Causes and treatment of refractory edema in adults".)
As an example, an initial IV bolus of 20 to 40 mg of furosemide administered over one to two minutes may be followed by a continuous infusion of approximately 5 mg/h in patients with relative intact renal function (estimated glomerular filtration [GFR] rate greater than 75 mL/min) and rates of up to 20 mg/h in patients with an estimated GFR less than 30 mL/min. Adding a thiazide diuretic may potentiate the effect, but hypokalemia should be avoided .
The onset of diuresis typically occurs within 30 minutes with peak diuresis usually at one to two hours after IV diuretic administration.
We suggest switching from an effective IV dose to an oral regimen once the patient’s acute symptoms have been stabilized to help ensure that an effective outpatient dose is identified and prescribed.
Evidence — No single IV dosing regimen (bolus versus continuous infusion; high versus lower dose) has been shown to be superior to others, as discussed separately. (See "Use of diuretics in patients with heart failure", section on 'Treatment of ADHF'.)
Monitoring — Volume status, evidence of congestion, oxygenation, daily weight, fluid intake, and output should be continually reassessed. Monitoring should also include watching for and guarding against side effects (including electrolyte abnormalities, symptomatic hypotension, worsening renal function and metabolic alkalosis). Diuretic therapy can also precipitate attacks of gout. The later transition from IV to oral diuretics should be made with careful attention to HF status, supine and upright hypotension, renal function, and electrolytes. (See "Loop diuretics: Dosing and major side effects" and "Diuretic-induced hyperuricemia and gout".)
Electrolytes — Serum potassium and magnesium levels should be monitored at least daily, and more frequent monitoring is indicated when diuresis is rapid, particularly since hypokalemia and hypomagnesemia increase the risk of arrhythmia. Severe muscle cramps may occur with overly rapid diuresis and should be treated with potassium and magnesium repletion if indicated .
Hemodynamic effects — By reducing intravascular volume, diuresis lowers central venous and pulmonary capillary wedge pressures. In addition, furosemide and possibly other loop diuretics also have an initial morphine-like effect in acute pulmonary edema, causing venodilation that can decrease pulmonary congestion prior to the onset of diuresis . This effect appears to be mediated by enhanced release of prostaglandins. (See "Use of diuretics in patients with heart failure", section on 'Venodilatory effect in acute pulmonary edema'.)
Careful monitoring during diuresis is required to prevent adverse hemodynamic effects by establishing the optimal rate and volume of diuresis for each patient. By reducing intravascular volume, diuresis may excessively lower central venous and pulmonary capillary wedge pressures, thereby decreasing LV preload to a degree that causes decreases in cardiac output and blood pressure, due to a lag in re-equilibration of intravascular volume via movement of fluid from the interstitial space. Patients with HF with preserved LV ejection fraction [LVEF] or restrictive physiology are often more sensitive to diuresis-induced reductions in preload. Diuretics may also enhance the hypotensive effects of angiotensin converting enzyme (ACE) inhibitor, angiotensin receptor-neprilysin inhibitor (ARNI) or single agent angiotensin receptor blocker (ARB) therapy even when volume overload persists.
Patterns of change — The blood urea nitrogen (BUN) and serum creatinine often rise during diuretic treatment of ADHF and careful monitoring is recommended. In the absence of other causes for an elevated BUN, a disproportionate rise in BUN relative to serum creatinine (BUN/serum creatinine ratio >20:1) suggests a prerenal state with increased passive reabsorption of urea. An initial rise in BUN may be accompanied by a stable serum creatinine, reflecting preserved GFR. Further elevations in BUN along with a rise in serum creatinine are likely if diuresis is continued in such patients. (See "Etiology and diagnosis of prerenal disease and acute tubular necrosis in acute kidney injury in adults", section on 'Blood urea nitrogen/serum creatinine ratio'.)
An otherwise unexplained rise in serum creatinine, which reflects a reduction in GFR, may be a marker of reduced perfusion to the kidney and other organs. Patients in whom this occurs before euvolemic status is achieved have a worse prognosis. Nevertheless, fluid removal may still be required to treat signs and symptoms of congestion, particularly pulmonary edema. On the other hand, a stable serum creatinine suggests that perfusion to the kidneys (and therefore to other organs) is being well maintained and that the diuresis can be continued if the patient is still edematous. (See "Cardiorenal syndrome: Definition, prevalence, diagnosis, and pathophysiology", section on 'Reduced renal perfusion' and "Cardiorenal syndrome: Prognosis and treatment", section on 'Change in glomerular filtration rate during therapy for heart failure'.)
Changes in cardiac output and the consequent changes in renal perfusion are not the only determinant of changes in GFR in patients with HF. Among patients with an elevated central venous pressure, the associated increase in renal venous pressure can reduce the GFR, while lowering venous pressure with diuretics and other therapies might therefore increase the GFR. (See "Cardiorenal syndrome: Definition, prevalence, diagnosis, and pathophysiology".)
Management of worsening renal function — Guidelines for management of patients with ADHF with elevated or rising BUN and/or serum creatinine include the following :
●Other potential causes of kidney injury (eg, use of nephrotoxic medications, urinary obstruction) should be evaluated and addressed.
●Patients with severe symptoms or signs of congestion, particularly pulmonary edema, require continued fluid removal independent of changes in GFR. In the presence of elevated central venous pressure, renal function may improve with diuresis. (See "Cardiorenal syndrome: Definition, prevalence, diagnosis, and pathophysiology", section on 'Increased renal venous pressure'.)
●If the BUN rises and the serum creatinine is stable or increases minimally, and the patient is still fluid overloaded, the diuresis can be continued to achieve the goal of eliminating clinical evidence of fluid retention with careful monitoring of renal function. (See "Use of diuretics in patients with heart failure", section on 'Goals of therapy'.)
●If increases in serum creatinine appear to reflect intravascular volume depletion, then reduction in or temporary discontinuation of diuretic and/or ACE inhibitor/ARB therapy should be considered. Adjunctive inotropic therapy may be required. (See 'Inotropic agents' below.)
●If substantial congestion persists and adequate diuresis cannot be achieved, then ultrafiltration, dialysis, or inotropes should be considered. (See "Kidney replacement therapy (dialysis) in acute kidney injury in adults: Indications, timing, and dialysis dose", section on 'Urgent indications'.)
Approach to vasodilator therapy — Vasodilators may be required to correct elevated filling pressures and/or LV afterload in patients with ADHF. The selection of vasodilator depends on the underlying hemodynamics. A vasodilator that decreases arterial tone (eg, nitroprusside) is recommended for patients with urgent need for afterload reduction (eg, severe hypertension). A vasodilator therapy that primarily decreases venous tone (eg, nitroglycerin) may be used as an adjunct to diuretic therapy for patients without an adequate response to diuretics. Vasodilator therapy is a component of therapy for patients with refractory HF and low cardiac output, as discussed below and separately. (See "Management of refractory heart failure with reduced ejection fraction", section on 'Approaches to specific refractory heart failure presentations'.)
We suggest early vasodilator therapy (typically, nitroprusside) in patients with severe hypertension, acute mitral regurgitation, or acute aortic regurgitation. Reliable blood pressure monitoring is required, and careful patient assessment is needed in determining the best vasodilator for the situation. These agents should be reduced or discontinued if symptomatic hypotension develops. (See "Acute mitral regurgitation in adults" and "Acute aortic regurgitation in adults".)
Use of vasodilator therapy in patients with ADHF is largely based upon hemodynamic response and expert opinion [4,5], since evidence on efficacy and safety of vasodilatory therapy in this setting is limited [12,13].
The routine use of vasodilators does not improve outcomes, and should be avoided . For example, the largest randomized trial of the routine use of nesiritide in patients with ADHF, ASCEND-HF, found that nesiritide showed a borderline significant trend toward reducing dyspnea, but increased rates of hypotension, and did not alter rates of death, rehospitalization at 30 days, or worsening renal function . Of note, the drug nesiritide is no longer available for clinical use.
Similarly, no improvement in a composite outcome of mortality and ADHF rehospitalization at 180 days was found in the randomized controlled GALACTIC trial with early and sustained use of nonparenteral vasodilators (with high doses of sublingual and transdermal nitrates, oral hydralazine for 48 hours, and rapid uptitration of ACE inhibitor, ARB, or ARNI) compared with usual care (with slower uptitration of ACE inhibitor, ARB, or ARNI) .
Nitroglycerin — Nitrates, the most commonly used vasodilators in ADHF, cause greater venous than arterial vasodilation. They reduce LV filling pressure primarily via venodilation. At higher doses, nitrates variably lower systemic vascular resistance and LV afterload, and may thereby increase stroke volume and cardiac output. Higher doses, however, should probably be limited to patients with hypertension and ADHF.
In patients with ADHF receiving nitrate therapy, an IV (rather than transdermal [ointment or patch] or oral) route is used for greater speed and reliability of delivery and ease of titration. An initial dose of 5 to 10 mcg/min of IV nitroglycerin is recommended with the dose increased in increments of 5 to 10 mcg/min every three to five minutes as required and tolerated (dose range 10 to 200 mcg/min). Similar benefits have been described with high-dose IV isosorbide dinitrate, where available [12,13]. However, if hypotension occurs, the longer half-life of isosorbide dinitrate compared with IV nitroglycerin (four hours versus three to five minutes) is a major disadvantage.
Potential adverse effects of nitroglycerin include hypotension and headache. Nitrate therapy should be avoided or used with caution in settings in which hypotension is likely or could result in serious decompensation such as right ventricular infarction or aortic stenosis. Nitrate administration is contraindicated after use of PDE-5 inhibitors such as sildenafil. (See "Sexual activity in patients with cardiovascular disease", section on 'Adverse interaction with nitrates' and "Right ventricular myocardial infarction", section on 'Optimization of right ventricular preload' and "Medical management of symptomatic aortic stenosis", section on 'Medical management'.)
Tachyphylaxis develops within 24 to 48 hours of continuous nitroglycerin administration. If diuretic therapy is effective during the initial period, the vasodilatory effects of nitroglycerin are commonly no longer required after this period. Blood pressure control after this initial period is achieved by transitioning to oral long-term therapy for HF as described below (see 'Approach to long-term therapy in hospitalized patients' below). We do not use a strategy of nitrate-free interval to reduce tolerance in patients with ADHF as this could result in adverse hemodynamic effects.
As noted in a systematic review of the limited studies comparing IV nitroglycerin with placebo in patients with acute HF, there was low-quality evidence of a decrease in mean pulmonary capillary wedge pressure with IV nitroglycerin compared with placebo, and there was low to moderate quality evidence of clinical benefit .
Some studies (including two small randomized trials of limited quality [12,13]) have suggested that treatment regimens for acute HF that include high-dose nitrate therapy (in the form of IV bolus nitroglycerin or high-dose IV isosorbide dinitrate) may provide greater clinical benefit (eg, reduced need for mechanical ventilation) than regimens including low-dose nitrate or no nitrate therapy . It has been proposed that high-dose nitrate therapy may be particularly helpful and well tolerated in patients presenting with hypertensive HF, but the supportive data are limited.
Nitroprusside — In contrast to nitroglycerin, nitroprusside causes balanced arterial and venous dilation. Thus, while it can be used to decrease LV filling pressures, it will cause a concomitant decrease in systemic vascular resistance. In patients in whom systemic resistance is elevated, the resulting decrease in afterload can increase stroke volume without lowering blood pressure; whereas if systemic vascular resistance is not elevated, nitroprusside may cause hypotension. Likewise, arterial dilation and afterload reduction can be of value in patients with depressed stroke volume due to elevated LV afterload such as acute aortic regurgitation, acute mitral regurgitation, acute ventricular septal rupture, or hypertensive emergency. (See "Drugs used for the treatment of hypertensive emergencies", section on 'Nitroprusside'.)
Because of its very potent hemodynamic effects and the potential to excessively lower blood pressure, the use of nitroprusside requires close hemodynamic monitoring, typically with an intra-arterial catheter. The initial dose of 5 to 10 mcg/min is titrated up every five minutes as tolerated to a dose range of 5 to 400 mcg/min.
The major limitation to the use of nitroprusside is its metabolism to cyanide. The accumulation of nitroprusside metabolites can lead to the development of cyanide, or rarely thiocyanate, toxicity, which may be fatal. Doses above 400 mcg/min generally do not provide greater benefit and may increase the risk of thiocyanate toxicity. Nitroprusside administration requires close and continuous blood pressure monitoring, and may cause reflex tachycardia. Another potential risk is rebound vasoconstriction upon discontinuation of nitroprusside . Thus, the use of nitroprusside is limited to selected patients, usually for durations of less than 24 to 48 hours.
Sodium and fluid restriction
Sodium restriction — Sodium restriction has been commonly recommended in patients with acute or chronic HF, although there are insufficient data to support any specific level of sodium intake in patients with symptomatic HF, as noted in the 2013 ACC/AHA and 2012 European Society of Cardiology (ESC) guidelines [5,19]. Given the available evidence, we suggest sodium restriction (eg, <2 g/d) in patients with symptomatic HF. The 2013 ACC/AHA guidelines suggest some degree (eg, <3 g/d) of sodium restriction in patients with symptomatic HF , while the 2012 ESC guidelines note that the safety and efficacy of salt restriction require further study . (See "Patient education: Low-sodium diet (Beyond the Basics)".)
Fluid restriction — Fluid restriction (eg, 1.5 to 2 L/d) may be helpful in patients with refractory HF and hyponatremia, as suggested by the 2013 ACC/AHA guidelines . Stricter fluid restriction is indicated in patients with severe (serum sodium <125 mEq/L) or worsening hyponatremia, although patient tolerance of strict fluid restriction may be limited. (See "Hyponatremia in patients with heart failure", section on 'Treatment' and "Overview of the treatment of hyponatremia in adults", section on 'Fluid restriction'.)
Hyponatremia is common among HF patients and the degree of reduction in serum sodium parallels the severity of the HF. As a result, a low serum sodium is an adverse prognostic indicator. Most HF patients with hyponatremia have volume overload rather than volume depletion.
Evidence — The evidence to support sodium and/or fluid restriction in patients with ADHF is inconclusive, with two small randomized trials of fluid restriction or fluid and sodium restriction in patients hospitalized with HF showing no benefit [20,21]. As an example, the second study randomly assigned 75 patients with ADHF due to systolic dysfunction treated with the usual pharmacologic interventions to a diet with a maximum dietary sodium intake of 800 mg/day and a maximum fluid intake of 800 mL/day or to a similar diet with 3 to 5 g of total sodium intake and a fluid intake of at least 2.5 L/day . At three days, weight loss was similar in both groups, as were measures of clinical congestion. Perceived thirst (graded on a scale of 0 to 10), was significantly worse in the group with stricter sodium and fluid intake (between group difference, 1.66 points).
Although some studies have suggested a possible benefit from a regimen of hypertonic saline plus furosemide in patients with ADHF, this approach is controversial and is of uncertain safety and efficacy. (See "Investigational therapies for management of heart failure".)
Venous thromboembolism prophylaxis — Prophylaxis against venous thromboembolism (deep vein thrombosis and pulmonary embolism) with low-dose unfractionated heparin or low molecular weight heparin, or fondaparinux, is indicated in patients admitted with ADHF who are not already anticoagulated and have no contraindication to anticoagulation. In patients admitted with ADHF who have a contraindication to anticoagulation, venous thromboembolism prophylaxis with a mechanical device (eg, intermittent pneumatic compression device) is suggested . These issues are discussed in detail separately. (See "Prevention of venous thromboembolic disease in acutely ill hospitalized medical adults".)
Vasopressin receptor antagonists — Vasopressin receptor antagonists have been investigated as an adjunct to diuretics and other standard therapies in patients with ADHF as a means of countering arterial vasoconstriction, hyponatremia, and water retention. Tolvaptan is the most studied agent in this setting. However, such treatment is controversial since the long-term safety and benefit of this approach are unknown. (See "Hyponatremia in patients with heart failure", section on 'Efficacy'.)
For patients with HF with volume overload with persistent severe hyponatremia (ie, serum sodium ≤120 mEq/L) despite water restriction and maintenance of guideline-directed medical therapy, short-term use of a vasopressin receptor antagonist (either a V2 receptor selective or nonselective vasopressin antagonist) is an option to improve serum sodium concentration . Cautions include hepatotoxicity (with the US Food and Drug Administration determining that tolvaptan should not be used in any patient for longer than 30 days and should not be used at all in patients with liver disease due to risk of liver failure or death) and overly rapid correction of hyponatremia, which can lead to irreversible neurologic injury. These issues are further discussed separately. (See "Hyponatremia in patients with heart failure", section on 'Vasopressin receptor antagonists'.)
Our approach is similar to the 2013 ACC/AHA guidelines, which classify as reasonable the short-term use of vasopressin antagonists in hospitalized patients with volume overload who have persistent severe hyponatremia and are at risk for cognitive symptoms despite water restriction and maximization of guideline-directed medical therapy, although the long-term safety and benefit of this approach are unknown . The 2012 ESC guidelines suggest consideration of tolvaptan for HF patients with hyponatremia in an ungraded recommendation .
Opiates — Given the limited evidence of benefits and potential risks of opiates, we suggest generally avoiding opiate therapy in the treatment of ADHF.
Data are limited on the effects of morphine therapy in ADHF. Morphine reduces patient anxiety and decreases the work of breathing. These effects diminish central sympathetic outflow, leading to arteriolar and venous dilatation with a resultant fall in cardiac filling pressures [22,23].
A systematic review that included one prospective and four retrospective studies of opiates (morphine or diamorphine) in ADHF found that the available evidence was very low quality, with no evidence of benefit and some evidence of harm . The largest of the studies found that morphine administration for ADHF was associated with increased frequency of mechanical ventilation, admission to an intensive care unit, and in-hospital mortality . After risk adjustment and exclusion of ventilated patients, morphine remained an independent predictor of mortality (OR 4.8, 95% CI 4.52-5.18). Two smaller studies found no significant differences in mortality rates with opiate therapy. Although risk adjustment in the largest study may not have been adequate, the results raise concern about the safety of opiate therapy in this population.
The 2012 ESC guidelines include consideration of opiates such as morphine in some patients with acute pulmonary edema as an ungraded recommendation, noting that they reduce anxiety and distress associated with dyspnea but also induce nausea and depress respiratory drive . Morphine therapy is not mentioned in the 2010 Heart Failure Society of America guidelines on management of ADHF or in the 2013 ACC/AHA guidelines.
The role of morphine sulfate in patients with ADHF who have an acute myocardial infarction is discussed separately. (See "Treatment of acute decompensated heart failure in acute coronary syndromes", section on 'Morphine sulfate'.)
MANAGEMENT OF HYPOTENSIVE PATIENTS
Approach to hypotension — The approach to acute HF and hypotension differs for HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF).
Treatment of patients with HFrEF and hypotension is guided by hemodynamics, which are most commonly imputed from the physical examination with more direct assessment by right heart catheterization performed when required for selected cases. If the systolic blood pressure is <85 mmHg or there is evidence of shock (eg, cool extremities, narrow pulse pressure, low urine output, confusion) and evidence of adequate preload, the addition of an inotrope is suggested . In patients with persistent shock, a vasopressor may be needed as a temporizing measure to support perfusion to vital organs, though this is at the expense of increased LV afterload. Selected patients with hypotension may benefit from vasodilator therapy guided by invasive monitoring, including pulmonary artery catheter. For selected patients with severe HFrEF (generally with LVEF <25 percent) with acute, severe hemodynamic compromise, nondurable mechanical support (eg, intra-aortic balloon pump [IABP], extracorporeal circulatory membrane oxygenator [ECMO], or extracorporeal ventricular assist devices) is an option as a "bridge to decision" or "bridge to recovery" [5,19].
Patients with HFpEF presenting with hypotension should not receive inotropic therapy and may require a vasopressor . Assessment of the intravascular volume status is critical in such patients to determine the need for diuresis and/or hydration. For patients who develop hypotension with dynamic LV outflow obstruction, treatment may include a beta blocker, a vasopressor (eg, phenylephrine or norepinephrine), and gentle hydration if pulmonary edema is not present. Dynamic LV outflow obstruction occurs in some patients with hypertrophic cardiomyopathy but is not limited to patients with that condition. (See "Hypertrophic cardiomyopathy: Management of patients with outflow tract obstruction", section on 'Acute shock'.)
Indications — Intravenous (IV) inotropic agents such as dobutamine and/or milrinone may be required as a temporizing measure in patients with severe LV systolic dysfunction and low output syndrome (diminished peripheral perfusion and end-organ dysfunction). We agree with the recommendations on inotropic agents in the 2013 American College of Cardiology Foundation/American Heart Association guideline on HF . Temporary IV inotropic support was recommended for patients with cardiogenic shock to maintain systemic perfusion and preserve end-organ performance until definitive therapy (eg, coronary revascularization, mechanical circulatory support, or heart transplantation) is instituted or resolution of the acute precipitating problem has occurred. Continuous IV inotropic support was felt to be reasonable as "bridge therapy" in patients with stage D HF refractory to guideline-directed medical therapy and device therapy who are eligible for and awaiting mechanical circulatory support or cardiac transplantation. In addition, the guidelines noted that inotropic therapy "may be reasonable" (a very weak recommendation) in the following settings: short-term, continuous IV inotropic support in hospitalized patients presenting with documented severe systolic dysfunction who present with low blood pressure and significantly depressed cardiac output to maintain systemic perfusion and preserve end-organ performance; and long-term continuous IV inotropic support as palliative therapy for symptom control in select patients with stage D HF despite optimal guideline-directed medical therapy and device therapy who are not eligible for either mechanical circulatory support or cardiac transplantation. (See "Palliative care for patients with advanced heart failure: Indications and systems of care".)
Patients receiving IV inotropes require continuous or frequent blood pressure monitoring and continuous monitoring of cardiac rhythm . Invasive hemodynamic monitoring is indicated in patients with respiratory distress or impaired systemic perfusion with uncertain hemodynamic status . If symptomatic hypotension or worsening tachyarrhythmias develop during inotrope administration, dose reduction or discontinuation is suggested.
Inotropes are not indicated for treatment of ADHF in the setting of preserved systolic function.
Patients with hypotension with dynamic LV outflow tract (LVOT) obstruction (who may have normal or depressed LV systolic function) should not receive inotropes since they can provoke or worsen the obstruction . Patients with dynamic LVOT obstruction are treated with beta blockers and careful fluid resuscitation in the absence of significant pulmonary congestion. Vasopressor therapy may be required for severe hypotension. (See "Management and prognosis of stress (takotsubo) cardiomyopathy", section on 'With left ventricular outflow tract obstruction'.)
Specific agents — The recommendations for dosing of the following inotropes are described elsewhere (table 3). (See "Management of refractory heart failure with reduced ejection fraction", section on 'Agents'.)
●Milrinone – Milrinone is a phosphodiesterase inhibitor that increases myocardial inotropy by inhibiting degradation of cyclic adenosine monophosphate. Milrinone is also a potent arterial and venous dilator due to inhibition of vascular smooth muscle phosphodiesterase, leading to decreases in systemic and pulmonary vascular resistance, and right and left heart filling pressures [26,27]. Together, these effects lead to an increase in cardiac index and decreases in LV afterload and filling pressures.
●Dobutamine – Dobutamine acts primarily on beta-1 adrenergic receptors, with minimal effects on beta-2 and alpha-1 receptors. The hemodynamic effects of dobutamine include increases in stroke volume and cardiac output, and modest decreases in systemic vascular resistance and pulmonary capillary wedge pressure [28,29].
●Dopamine – At low doses of 1 to 3 mcg/kg per min, dopamine acts primarily on dopamine-1 receptors to dilate the renal and mesenteric artery beds . At 3 to 10 mcg/kg per min (and perhaps also at lower doses), dopamine also stimulates beta-1 adrenergic receptors and increases cardiac output, predominantly by increasing stroke volume with variable effects on heart rate. At medium-to-high doses, dopamine also stimulates alpha-adrenergic receptors, although a small study suggested that renal arterial vasodilation and improvement in cardiac output may persist as the dopamine dose is titrated up to 10 mcg/kg per min .
Although it has been proposed that dopamine might improve renal function in patients with severe HF by increasing renal blood flow and possibly by reducing renal venous pressure, data supporting such a potential benefit are limited. Specifically, the addition of low-dose dopamine to diuretic therapy was not found to enhance decongestion or improve renal function . (See "Cardiorenal syndrome: Prognosis and treatment", section on 'Inotropic drugs'.)
Evidence — A systematic review of randomized controlled trials of inotropes in ADHF found that evidence was insufficient to determine the clinical efficacy and safety of such therapy .
There is concern that inotropic agents may adversely impact outcomes in patients with ADHF with congestion without a low output state [32,33]. Inotropic agents may increase heart rate and myocardial oxygen consumption and thus provoke ischemia and potentially damage hibernating but viable myocardium, particularly in patients with ischemic heart disease. In addition, inotropic agents can increase atrial  and ventricular  arrhythmias. Given these concerns, careful patient selection is required for inotrope use. (See "Use of vasopressors and inotropes" and "Inotropic agents in heart failure with reduced ejection fraction", section on 'Intravenous therapy'.)
Routine use of inotropes in patients hospitalized for HF was found to be harmful in the OPTIME-CHF trial . In this trial, 949 patients admitted to the hospital with an acute exacerbation of chronic HF were randomly assigned to a 48- to 72-hour infusion of milrinone or placebo. Due to its vasodilator actions, milrinone therapy was associated with significant increases in hypotension requiring intervention and atrial arrhythmias, and was associated with nonsignificant increases in mortality in-hospital (3.8 versus 2.3 percent) and at 60 days (10.3 versus 8.9 percent). This trial did not evaluate patients whose treating physicians felt could not be randomized, but demonstrates overall adverse effects in noncritical patients despite improved symptoms.
The general role of inotropic agents in patients with HFrEF is discussed separately. (See "Inotropic agents in heart failure with reduced ejection fraction", section on 'Intravenous therapy'.)
Vasopressor therapy — In patients with ADHF and marked hypotension, vasopressor therapy can be used as a temporizing measure to preserve systemic blood pressure and end-organ perfusion, although at the cost of increasing afterload and decreasing cardiac output . Vasopressor use should be limited to patients with persistent hypotension with symptoms or evidence of consequent end-organ hypoperfusion despite optimization of filling pressures and use of inotropic agents as appropriate. In this setting, invasive monitoring can be helpful to assess filling pressures and systemic vascular resistance. (See "Pulmonary artery catheterization: Indications, contraindications, and complications in adults", section on 'Indications'.)
Vasopressors used in this setting include norepinephrine, high-dose dopamine (>5 micrograms/kg/min), and vasopressin, and these should be carefully titrated to achieve adequate perfusion of vital organs (table 3). Dopamine and norepinephrine have beta inotropic as well as vasopressor activity. (See "Use of vasopressors and inotropes".)
A systematic review found no evidence to determine the clinical efficacy and safety of vasopressor therapy in ADHF .
Mechanical cardiac support — For selected patients with severe HFrEF (generally with LVEF <25 percent) with acute, severe hemodynamic compromise (cardiogenic pulmonary edema with cardiogenic shock), nondurable mechanical support is an option as a “bridge to decision” or “bridge to recovery” [5,19]. These patients usually have a cardiac index less than 2.0 L/min per m2, a systolic arterial pressure below 90 mmHg, and a pulmonary capillary wedge pressure above 18 mmHg, despite adequate pharmacologic therapy. (See "Management of refractory heart failure with reduced ejection fraction", section on 'Mechanical circulatory support'.)
Mechanical modalities used in this setting include IABP, ECMO, or short-term LV assist devices. (See "Intraaortic balloon pump counterpulsation" and "Short-term mechanical circulatory assist devices".)
APPROACH TO LONG-TERM THERAPY IN HOSPITALIZED PATIENTS
●Determine if the patient is stable – In patients with ADHF, the patient’s stability determines whether long-term therapy can be continued or initiated. While the degree of stability required for long-term HF therapy is ultimately based on a clinical judgement influenced by many factors, stable patients who can tolerate continuation of their chronic HF therapy in the hospital typically have the following features:
•Systolic blood pressure ≥100 mmHg
•Heart rate less than 100 beats per minute
•Absence of cardiogenic shock
•No requirement for intravenous (IV) diuretics or IV vasodilators in the preceding six hours
•No requirement for IV inotropes in the preceding 24 hours
•Normal or improving kidney function
These features are based on our clinical experience and definitions used in trials of ADHF [35,36].
●Changes to long-term therapy in stable patients – Patients with ADHF who are stable may continue or undergo changes to their long-term HF regimen:
•Continuation of therapy – In patients with ADHF who exhibit signs of clinical stability at presentation, long-term therapy can be continued during the inpatient admission if it is unlikely to cause harm. However, patients who continue their long-term HF medications should be frequently evaluated for signs of instability to determine whether any component of such therapy should be discontinued or have its dose reduced.
There are no trials that compare continued long-term HF therapy with interrupted therapy in patients with ADHF. In retrospective studies of patients with ADHF, patients who continue long-term therapy had a lower risk of mortality, but this finding is likely the result of bias (ie, low-risk patients can safely continue long-term therapy, while high-risk patients have their long-term therapy discontinued) [37-41].
•Resuming, starting, or adjusting outpatient therapy – In patients with ADHF who are or become stable, we attempt to resume, initiate, or adjust long-term HF therapies prior to discharge. In highly selected inpatients scheduled for discharge and who can reliably undergo frequent observation in the outpatient setting, HF medications can be added or adjusted toward their target doses. The severity of HF determines the type and dose of any medication change.
Inpatients who cannot tolerate low doses of long-term HF therapies (eg, those with hypotension or tachycardia) should be monitored for other signs of decompensation (eg, residual volume overload) and if further management results in stability, such patients may be rechallenged with a low dose of a single agent. (See "Systems-based strategies to reduce hospitalizations in patients with heart failure", section on 'Inpatient and transitional care strategies'.)
The preferred treatments for HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF) and the approach to dosing are described elsewhere:
-Therapy for HFrEF. (See "Primary pharmacologic therapy for heart failure with reduced ejection fraction".)
Our approach is based on the observations that patients hospitalized with HF are more unstable and susceptible to adverse drug effects [42-45] but may have a lower risk of readmission with optimal use of pharmacologic therapy. The safety and efficacy of optimal medication use in patients recently hospitalized was evaluated in dedicated trials that include:
-In a trial of medication changes that included 1078 patients with HFrEF and HFpEF who were admitted with acute HF decompensation, assignment to high-intensity care (ie, dose adjustment to target within two weeks of discharge, four outpatient visits within two months) resulted in a higher likelihood of patients receiving target doses of HF medications (eg, beta blocker target dose achieved in 49 versus 4 percent in the usual care group) . In addition, the rate of HF readmission was lower in the high-intensity group (9.5 versus 17.1 percent at 180 days; adjusted risk ratio [RR] 0.56, 95% CI 0.38-0.81), and all-cause mortality rates were similar (8.5 versus 10 percent in the usual care group; adjusted RR 0.84, 95% CI 0.56-1.26). The rates of serious adverse events were similar between the two groups. In the subgroup of patients with HF and LVEF ≤40 percent (n = 692), the results were similar to the main results of the trial (interaction p value = 0.27).
Notably, the mean blood pressure in the trial sample was 123 mmHg (standard deviation [SD] 13 mmHg) and mean N-terminal pro-B-type natriuretic peptide was 7111 ng/L (SD 4675 ng/L).
●Long-term therapy in unstable patients – Patients hospitalized with ADHF who are unstable or who have advanced HF symptoms are often not candidates for continuation or immediate initiation of some long-term therapies for HF. In these patients, we adjust medications based upon factors such as blood pressure, heart rate, renal function, etiology of decompensation, and the effect of the particular agent. If safe, we prefer to continue treatment and reevaluate for signs of stability before initiating long-term therapy.
This approach is based on the potential for long-term HF therapies to cause harm in patients with ADHF; these agents have a relatively long half-life and affect blood pressure, kidney function, electrolyte handling, and diuresis. In patients undergoing treatment for ADHF, the patient’s response to HF decompensation (eg, elevated catecholamines) and to the treatments for HF (eg, large volume diuresis, vasodilation) can interact and lead to complications such as hypotension, hyperkalemia, and worsening acute kidney injury. Thus, short-acting therapies with less effect on the kidney are preferred over long-term therapies for HF. (See 'Management of worsening renal function' above and 'Approach to vasodilator therapy' above and 'Approach to hypotension' above.)
●Specific scenarios and agents – The following are common scenarios that may require specific changes to therapy:
•Severely decompensated HFrEF – In patients with severely decompensated HFrEF, beta blockers should be discontinued due to their negative inotropic effect. Similarly, ivabradine should not be used to treat tachycardia caused by severely decompensated heart failure or cardiogenic shock.
•Worsening kidney function – In patients with worsening kidney function, some long-term therapies may further worsen kidney function (eg, ACE inhibitors, angiotensin receptor blockers), exacerbate the effects of kidney dysfunction (eg, hyperkalemia caused by spironolactone), or cause toxicity (eg, digoxin). Thus, the components of long-term therapy should be evaluated for discontinuation if kidney function is declining. (See 'Management of worsening renal function' above.)
•Patients who are fasting who have diabetes and take SGLT2 inhibitor – Patients with diabetes who undergo prolonged fasting and concurrent treatment with an SGLT2 inhibitor are at risk of euglycemic diabetic ketoacidosis (ie, DKA). Thus, patients with diabetes should only receive SGLT2 inhibitors if their risk of DKA is low. (See "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Diabetic ketoacidosis'.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Heart failure in adults".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: When your lungs fill with fluid (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Initial therapy – Initial therapy includes supplemental oxygen to treat hypoxemia (SpO2 <90 percent), assisted ventilation if necessary, and a loop diuretic for volume overload (table 1). (See 'Supplemental oxygen and assisted ventilation' above.) (Related Pathway(s): Acute decompensated heart failure: Initial management of hypervolemic patients with adequate perfusion.)
•Supplemental oxygen and assisted ventilation – For patients with acute decompensated heart failure (ADHF) with respiratory distress, respiratory acidosis, and/or hypoxia with oxygen therapy, we recommend a trial of noninvasive ventilation (NIV) if emergent intubation is not indicated (algorithm 1), no contraindications to NIV exist (table 2), and personnel with experience in NIV are available (Grade 1A). (See 'Supplemental oxygen and assisted ventilation' above and "Noninvasive ventilation in adults with acute respiratory failure: Benefits and contraindications", section on 'Acute cardiogenic pulmonary edema (ACPE)'.)
Patients with respiratory failure due to ADHF who fail to improve with NIV (within one-half to two hours), do not tolerate NIV, or have contraindications to NIV (table 2) require endotracheal intubation for conventional mechanical ventilation. (See "Overview of initiating invasive mechanical ventilation in adults in the intensive care unit".)
•Diuretics – In patients with ADHF and fluid overload, we recommend that initial therapy include a loop diuretic (administered intravenously [IV]) (Grade 1B) (see 'Diuretics' above). Dosing is individualized, determined largely by the patient's renal function and prior diuretic exposure. (See 'Diuretic administration' above and 'Renal function' above.)
-Patients with severe hypertension – For patients with urgent need for afterload reduction for severe hypertension or as a temporizing measure in patients with acute aortic regurgitation or acute mitral regurgitation, we suggest balanced vasodilator therapy (eg, nitroprusside) (Grade 2C). (See "Acute mitral regurgitation in adults" and "Acute aortic regurgitation in adults".)
-Patients who do not respond to diuretics – We suggest use of vasodilator therapy (eg, nitroglycerin) as an adjunct to diuretic therapy for patients without adequate response to diuretics (Grade 2C). (See "Management of refractory heart failure with reduced ejection fraction", section on 'Approach to refractory volume overload'.)
-Patients with refractory HF with reduced ejection fraction (HFrEF) and low cardiac output – We suggest vasodilator therapy as a component of therapy for patients with refractory HF and low cardiac output due to systolic dysfunction (Grade 2C). (See "Management of refractory heart failure with reduced ejection fraction", section on 'Approach to low cardiac output'.)
•Inotropes – IV inotropic agents such as dobutamine and/or milrinone may be required as a temporizing measure in patients with severe left ventricular (LV) systolic dysfunction and low output syndrome (diminished peripheral perfusion and end-organ dysfunction) (table 3). (See 'Inotropic agents' above.)
●Patients with HFpEF – Patients with HF with preserved ejection fraction (HFpEF) presenting with hypotension should not receive inotropes and may require a vasopressor in addition to diuretic therapy. Patients who develop hypotension with dynamic LV outflow obstruction are treated with beta blocker therapy and gentle hydration if pulmonary edema is not present. (See 'Approach to hypotension' above.)
●Long-term therapy – In patients with ADHF, the patient’s stability determines whether long-term therapy (eg, sacubitril/valsartan, beta blockers), can be continued, initiated, or adjusted. (See 'Approach to long-term therapy in hospitalized patients' above.)
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