Treatment of acute decompensated heart failure: Components of therapy

Author:
Wilson S Colucci, MD
Section Editors:
Stephen S Gottlieb, MD
James Hoekstra, MD
Deputy Editor:
Susan B Yeon, MD, JD, FACC

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review
process is complete.
Literature review current through: Jun 2018. | This topic last updated: Aug 25,
2017.

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)
[1]. ADHF can also present as elevated left ventricular filling pressures and dyspnea
without pulmonary edema.

ADHF is most commonly due to left ventricular 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 acute decompensated heart failure in adults".)

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".)

INITIAL THERAPY

Approach to general management — Patients presenting with acute dyspnea from

acute decompensated heart failure (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 access

●Seated posture

●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 diuretic for volume
overload.

Early intravenous vasodilator therapy is suggested in selected patients with ADHF

who require a decrease in systemic vascular resistance and left ventricular afterload
(eg, those with severe hypertension, acute mitral regurgitation, or acute aortic
regurgitation). 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. 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 [2].

For patients requiring supplemental oxygen, we suggest initial therapies in the

following order:

●Non-rebreather facemask delivering high-flow percent oxygen.

●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 acute respiratory
failure in adults", section on 'Cardiogenic pulmonary edema'.)

●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
mechanical ventilation" 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.

Diuretics — Patients with ADHF and evidence of volume overload, regardless of

etiology, should be promptly treated with intravenous diuretics as part of their initial
therapy [3-5]. 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 [4]. The expeditious initiation of an effective 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 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) [6]. 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. 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 intravenous diuretics can relieve symptoms and
improve oxygenation. Intravenous rather than oral administration is recommended
because of greater and more consistent drug bioavailability.

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 [7].

Diuretic administration

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 intravenous doses of loop diuretics in patients with
normal renal function:

•Furosemide – 20 to 40 mg intravenously

•Bumetanide – 1 mg intravenously

•Torsemide – 10 to 20 mg intravenously

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 intravenous 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 [8]. (See "Treatment of refractory edema in adults",
section on 'Basic principles of diuretic dosing' and "Treatment of refractory
edema in adults", section on 'Maximum effective dose of loop diuretics'.)

●Patients treated with loop diuretics chronically may need a higher dose in the
acute setting; the initial intravenous dose should be equal to or greater than (eg,
2.5 times) their maintenance total daily oral dose and then adjusted depending
upon the response (eg, an initial intravenous furosemide dose of 40 to 100 mg
for a patient who had been taking 40 mg orally per day). In the DOSE trial of
intravenous furosemide in patients with ADHF, there was an almost significant
trend toward greater improvement in patients’ global assessment of symptoms
in the high-dose (2.5 times the patients’ prior total daily diuretic dose) group
compared with the low-dose (equal to the prior total daily dose) group, as
discussed below [9]. 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 intravenous infusion is an alternative to intravenous bolus therapy,
although data are limited [10]. Use of a continuous intravenous infusion requires that
the patient be responsive to intravenous 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 intravenous bolus dose. (See "Treatment of
refractory edema in adults", section on 'Regimen' and "Use of diuretics in patients
with heart failure".)

As an example, an initial intravenous 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 [8].

The onset of diuresis typically occurs within 30 minutes with peak diuresis usually at
one to two hours after intravenous diuretic administration.

We suggest switching from an effective intravenous 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 intravenous 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 intravenous to oral diuretics should be made with careful attention to HF status,
supine and upright hypotension, renal function, and electrolytes. (See "Loop
diuretics: Maximum effective dose 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 [3].

Hemodynamic effects — Careful monitoring during diuresis is required to prevent

adverse hemodynamic effects. By reducing intravascular volume, diuresis will
eventually lower central venous and pulmonary capillary wedge pressures. In
addition, furosemideand 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 [11]. 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'.)

Reductions in right and left heart filling pressures with diuresis are frequently
associated with augmented forward stroke volume and cardiac output. Improved
forward stroke volume is related to decreases in functional tricuspid and mitral
regurgitation and reduction in right ventricular volume with relief of interdependent
left ventricular compression and improved left ventricular distensibility [3].
(See "Cardiorenal syndrome: Definition, prevalence, diagnosis, and
pathophysiology", section on 'Right ventricular dilatation and dysfunction'.)

However, during diuresis, some patients experience symptomatic hypotension with

decreasing cardiac output and systemic 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 left ventricular ejection fraction or restrictive
physiology may be more sensitive to diuresis-induced reductions in preload. Diuretics
may enhance the hypotensive effects of angiotensin converting enzyme (ACE)
inhibitor or angiotensin receptor blocker (ARB) therapy even when volume overload
persists.
Renal function

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 GFR during therapy for HF'.)

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 [3]:

●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 or dialysis should be considered. (See "Renal replacement
therapy (dialysis) in acute kidney injury in adults: Indications, timing, and dialysis
dose", section on 'Urgent indications'.)

Vasodilator therapy

Approach to vasodilator therapy — Vasodilators may be required to correct

elevated filling pressures and/or left ventricular afterload in patients with ADHF.
Indications for vasodilator therapy in the setting of ADHF include the following: early
vasodilator therapy (eg, nitroprusside) is recommended for patients with urgent need
for afterload reduction (eg, severe hypertension); vasodilator therapy
(eg, nitroglycerin) is suggested as an adjunct to diuretic therapy for patients without
adequate response to diuretics; and 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 [3,4], 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
[14]. 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
[15]. As such, we recommend not treating patients routinely with nesiritide.
(See "Nesiritide in the treatment of acute decompensated heart failure".)

Nitroglycerin — Nitrates, the most commonly used vasodilators in ADHF, cause

greater venous than arterial vasodilation. They reduce left ventricular 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.

In patients with ADHF receiving nitrate therapy, an intravenous (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
intravenous 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
intravenous isosorbide dinitrate, where available [12,13]. However, if hypotension
occurs, the longer half-life of isosorbide dinitrate compared with intravenous
nitroglycerin (four hours versus three to five minutes) is a major disadvantage.

Tachyphylaxis can occur within hours with administration of high doses

of nitroglycerin and the strategy of nitrate-free interval used to reduce tolerance
during chronic therapy could result in adverse hemodynamic effects in patients with
ADHF. 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'.)

As noted in a systematic review of the limited studies comparing

intravenous nitroglycerin with placebo in patients with acute HF, very low-quality
evidence showed a decrease in mean pulmonary capillary wedge pressure with
intravenous nitroglycerin compared with placebo but evidence of clinical benefit was
lacking [14].

Nitroprusside — In contrast to nitroglycerin, nitroprusside causes balanced arterial

and venous dilation. Thus, while it can be used to decrease left ventricular 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 left ventricular 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 nitroprussiderequires 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 [16]. Thus, the use of
nitroprusside is limited to selected patients, usually for durations of less than 24 to 48
hours.

Use of nitroprusside in patients with ADHF is based largely upon expert opinion since
available published evidence is very limited [14].

Nesiritide — Nesiritide, like nitroprusside, is a balanced arterial and venous dilator.

We recommend against routine treatment of patients with ADHF with nesiritide. In
carefully selected patients with appropriate hemodynamics (including absence of
hypotension or cardiogenic shock) who remain symptomatic despite routine therapy,
a trial of nesiritide may be helpful as an alternative to other vasodilator therapy
(nitroglycerin or nitroprusside).

Nesiritide is typically given as an initial intravenous bolus of 2 mcg/kg, followed by a

continuous infusion of 0.01 mcg/kg per minute, with subsequent dose adjustment as
necessary. Close monitoring of hemodynamics, urine output, and renal function are
necessary for effective clinical use and safety.

Nesiritide is less potent than nitroprusside, and both the onset and offset of action
are slower. Because nesiritide has a longer effective half-life than nitroglycerin or
nitroprusside, side effects such as hypotension may persist longer. (See "Nesiritide in
the treatment of acute decompensated heart failure", section on 'Use'.)

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 [4,17].
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 [17], while the 2012
ESC guidelines note that the safety and efficacy of salt restriction require further
study [17]. (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 [4].
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".)

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 [18,19]. 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 [19]. 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 and
emerging strategies 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 [3]. 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 V2receptor selective or nonselective vasopressin antagonist) is an option to
improve serum sodium concentration [4]. Cautions include hepatotoxicity (with the
United States Food and Drug Administration determining that tolvaptan should
be 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 [4]. The 2012 ESC guidelines suggest consideration of tolvaptan for HF
patients with hyponatremia in an ungraded recommendation [17].

Opiate — 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 [20,21].

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 [14]. 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 [22]. 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 [17]. 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), addition of an
inotrope is suggested [17]. In patients with persistent shock, a vasopressor may be
added as a temporizing measure to support perfusion to vital organs, though this is
at the expense of increased left ventricular 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 left ventricular ejection fraction [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" [4,17].

Patients with HFpEF presenting with hypotension should not receive inotropic
therapy and may require a vasopressor in addition to diuretic therapy. Patients who
develop hypotension with dynamic left ventricular outflow obstruction are treated with
beta blocker therapy, a vasopressor (eg, phenylephrine or norepinephrine), and
gentle hydration if pulmonary edema is not present. Dynamic left ventricular outflow
obstruction occurs in some patients with hypertrophic cardiomyopathy but is not
limited to patients with that condition. (See "Hypertrophic cardiomyopathy: Medical
therapy", section on 'Acute hemodynamic collapse in the setting of LVOT
obstruction'.)

Inotropic agents

Indications — Intravenous inotropic agents such

as dobutamine and/or milrinone may be required as a temporizing measure in
patients with severe left ventricular 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 [4]. Temporary
intravenous 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 intravenous 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 intravenous 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 intravenous
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 strategies".)

Similar recommendations are included in the 2010 Heart Failure Society of America
[3] and 2012 European Society of Guidelines [17].

Patients receiving intravenous inotropes require continuous or frequent blood

pressure monitoring and continuous monitoring of cardiac rhythm [3]. Invasive
hemodynamic monitoring is indicated in patients with respiratory distress or impaired
systemic perfusion with uncertain hemodynamic status [4]. 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 left ventricular outflow tract obstruction (who
may have normal or depressed left ventricular systolic function) should not receive
inotropes since they can provoke or worsen the obstruction [23]. Patients with
dynamic left ventricular outflow tract 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 "Hypertrophic
cardiomyopathy: Medical therapy", section on 'Heart failure' and "Management and
prognosis of stress (takotsubo) cardiomyopathy", section on 'With left ventricular
outflow tract obstruction'.)

Specific agents — Careful titration is advised when inotropes are used in patients
with ADHF (table 3) [4]:

●Milrinone – Milrinone is a phosphodiesterase inhibitor that increases

myocardial inotropy by inhibiting degradation of
cyclic adenosine monophosphate. Other direct effects of milrinone include
reducing systemic and pulmonary vascular resistance (via inhibition of
peripheral phosphodiesterase) and improving left ventricular diastolic
compliance [24,25]. These changes lead to an increase in cardiac index and
decrease in left ventricular afterload and filling pressures. Patients should
receive a loading dose of 50 mcg/kg over 10 minutes, followed by a
maintenance dose of 0.375 to a maximum of 0.750 mcg/kg per min. Dose
adjustment is required in the presence of renal insufficiency, hypotension, or
arrhythmias.
 Since milrinone does not act via beta receptors, its effects are not as diminished
as those of dobutamine or dopamine by concomitant beta blocker therapy.

●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 [26,27]. It should be started at 2.5 mcg/kg per min and, if tolerated and
needed, can be gradually increased to 20 mcg/kg per min.

●Dopamine – At low doses of 1 to 3 µg/kg per min, dopamine acts primarily on

dopamine-1 receptors to dilate the renal and mesenteric artery beds [28]. At 3 to
10 µg/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 µg/kg per min [28].

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 [29]. (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 [14].

There is concern that inotropic agents may adversely impact outcomes in patients
with ADHF with congestion without a low output state [30,31]. 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 [30] and
ventricular [32] arrhythmias. Given these concerns, careful patient selection is
required for inotrope use. (See "Inotropic agents in heart failure with reduced ejection
fraction" and "Use of vasopressors and inotropes".)

Routine use of inotropes in patients hospitalized for HF was found to be harmful in

the OPTIME-CHF trial [30]. 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. Milrinone therapy was associated with significant
increases in hypotension requiring intervention and atrial arrhythmias, and 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".)

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 [17]. 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 [14].

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” [4,17]. 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 left
ventricular assist devices. (See "Intraaortic balloon pump
counterpulsation" and "Short-term mechanical circulatory assist devices".)

CONTINUATION OR INITIATION OF LONG-TERM THERAPY — The approach to

managing long-term therapy during hospitalization for acute heart failure (HF) differs
for HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction
(HFpEF).

Approach to long-term therapy for heart failure with preserved ejection

fraction — The general principles for treatment of HFpEF are control of systolic and
diastolic hypertension, control of heart rate (particularly in patients with atrial
fibrillation), control of pulmonary congestion and peripheral edema with diuresis (with
care to avoid hypotension and/or left ventricular outflow obstruction), and treatment
of associated conditions (eg, coronary artery disease). (See "Treatment and
prognosis of heart failure with preserved ejection fraction".)

For patients with HFpEF who are hemodynamically stable during an acute
decompensated HF (ADHF) episode, chronic antihypertensive therapy may be
continued with careful monitoring. However, some patients with acute HF have
severe hypertension that may require parental vasodilator therapy [33]. On the other
hand, some patients with small left ventricular cavities and/or left ventricular
hypertrophy are volume-sensitive and at risk for developing hypotension with
diuresis. After the patient is stabilized and prior to discharge, an oral medical regimen
should be instituted, including antihypertensive and diuretic therapy as needed.
(See "Treatment and prognosis of heart failure with preserved ejection fraction",
section on 'Treatment'.)

Approach to long-term therapy for heart failure with reduced ejection

fraction — Evidence-based pharmacologic therapy to reduce morbidity and mortality
for patients with chronic HFrEF includes an angiotensin converting enzyme (ACE)
inhibitor, single-agent angiotensin receptor blocker (ARB), or angiotensin receptor-
neprilysin inhibitor (ARNI); a beta blocker; and a mineralocorticoid receptor
antagonist (MRA). During an acute HF episode, management of these agents
depends upon whether the patient was already receiving these medications and
whether the patient has contraindications to therapy such as hemodynamic instability
or acute kidney injury. Once the patient is stable, evidence-based therapies are
carefully initiated, re-initiated, or titrated with arrangements for appropriate outpatient
follow-up. In stable patients, ACE inhibitor, ARB, or ARNI and beta blocker therapy
should be initiated prior to hospital discharge and MRA should be added prior to or
soon after discharge (as needed to allow appropriate monitoring of serum potassium
levels). (See "Overview of the therapy of heart failure with reduced ejection
fraction" and "Pharmacologic therapy of heart failure with reduced ejection fraction".)

ACE inhibitor, ARB, or ARNI — For patients with HFrEF, an ACE inhibitor (or ARB
if ACE inhibitor is not tolerated) or ARNI is a mainstay of chronic therapy. (See "Use
of angiotensin converting enzyme inhibitors in heart failure with reduced ejection
fraction" and "Use of angiotensin II receptor blocker in heart failure with reduced
ejection fraction" and "Use of angiotensin receptor-neprilysin inhibitor in heart failure
with reduced ejection fraction".)

Continued therapy — For patients who are already taking an ACE inhibitor, single-
agent ARB, or ARNI, we suggest that maintenance of oral therapy be cautiously
continued. However, the dose should be decreased or the drug discontinued if
hypotension, worsening renal function, or hyperkalemia is present.

With regard to hypotension, two additional points should be considered:

●Some patients with chronic HF and severe left ventricular systolic dysfunction
tolerate relatively low blood pressures (eg, systolic blood pressure 90 to 100
 mmHg). Such patients often tolerate chronic ACE inhibitor, ARB, or ARNI
therapy and may tolerate these drugs in the acute setting as well.

●Patients with acute pulmonary edema may initially be hypertensive due to high
catecholamine levels during the early period of distress. With initial therapy,
blood pressure may fall rapidly and patients may become relatively hypotensive,
particularly if they are aggressively diuresed. Thus, long-acting drugs, such as
ACE inhibitors, ARBs, or ARNI should be administered with caution or avoided
during the first few hours of hospitalization.

Initiation of therapy — For patients who are not already taking an ACE inhibitor,
single-agent ARB, or ARNI, we suggest notinitiating such therapy at the time of
presentation with an episode of ADHF.

Although some have advocated early use of intravenous ACE inhibitor in patients
with ADHF, we do not recommend this approach. There are limited data on the
safety and efficacy of initiating new ACE inhibitor (or ARB) therapy in the early phase
of therapy of ADHF (ie, the first 12 to 24 hours) [34].

Major concerns with early therapy include:

●Patients with ADHF may develop hypotension and/or worsening renal function
during initial therapy. Determining the pathogenesis of such complications is
more difficult if an ACE inhibitor or ARB has been given. Hypotension following
administration of these agents may be prolonged given the long effective half-
lives of these agents.

●The intravenous ACE inhibitor enalaprilat may have deleterious effects in

patients with an acute myocardial infarction (MI), especially when complicated
by HF or aggressive diuresis [35,36]. Thus, intravenous enalaprilat is
contraindicated in acute MI and not generally recommended in other patients
with ADHF, although it is potentially useful in certain situations [34,36]. Other
agents are available, if needed, to treat refractory hypertension.

Early initiation of oral ACE inhibitor (or single agent ARB or ARNI) therapy is
also not recommended (except for early oral ACE inhibitor use in those with acute
MI) and should be avoided in patients at high risk for hypotension (eg, low baseline
blood pressure or hyponatremia, which is a marker for increased activation of the
renin-angiotensin system and therefore increased dependence upon angiotensin II
for blood pressure maintenance). In addition, aggressive diuretic therapy typically
given for acute pulmonary edema may increase sensitivity to ACE inhibition or
angiotensin blockade, including risks of hypotension and renal dysfunction.
(See "Angiotensin converting enzyme inhibitors and receptor blockers in acute
myocardial infarction: Recommendations for use" and "Pathophysiology of heart
failure: Neurohumoral adaptations" and "Hyponatremia in patients with heart failure".)

An oral ACE inhibitor or ARB can usually be started 24 to 48 hours after

presentation, once the patient is hemodynamically stable. Initiation of these therapies
known to improve outcomes is recommended prior to hospital discharge. We reserve
use of the ARNI sacubitril-valsartan for selected patients with HFrEF who have
tolerated high doses of ACE inhibitor (or ARB) therapy (equivalent to at
least enalapril 10 mg twice daily) for at least four weeks. However, some experts
recommend sacubitril-valsartan as initial oral therapy (in place of ACE inhibitor or
single-agent ARB) once the patient is hemodynamically stable. (See "Use of
angiotensin converting enzyme inhibitors in heart failure with reduced ejection
fraction".)

Beta blocker — Beta blockers reduce mortality when used in the long-term
management of patients with HFrEF, but must be used cautiously in patients with
decompensated HFrEF because of the potential to worsen acute HF. (See "Use of
beta blockers in heart failure with reduced ejection fraction".)

Thus, in patients with acute decompensated HFrEF, we approach the use of beta
blockers in the following manner:

●For patients who are already taking a beta blocker, management depends
upon the severity of HF decompensation and hemodynamic instability:

•For patients with severe decompensation (eg, severe volume

overload and/or requiring inotropic support), we suggest withholding beta
blockers.

•For patients with moderate-to-severe decompensation or hypotension, we

suggest decreasing or withholding beta blocker therapy.

•For patients with mild decompensation without hypotension or evidence of

hypoperfusion, we suggest continuation of beta blocker as tolerated.

Support for continuation of beta blocker therapy with mild decompensation

comes from retrospective analyses of patients enrolled in randomized trials
[37,38] and reports from the OPTIMIZE-HF program and the Italian Survey on
Acute Heart Failure [39,40]. Withdrawal of beta blocker therapy was associated
with increased mortality, as compared with continuation of such therapy.
However, these retrospective analyses cannot definitively determine whether
the discontinuation was the cause of the worse outcome. While the increase in
mortality was only partially explained by greater clinical risk factors in the
patients withdrawn from beta blocker therapy, such analyses cannot account for
all factors. For more severely ill patients, halving of the dose of beta blockers or
discontinuation may be necessary.

●For patients who are not already taking a beta blocker, we suggest that a beta
blocker not be initiated at the time of presentation with an episode of ADHF.
Beta blockers are started at low doses and are generally started later than ACE
inhibitors or ARBs, when the patient is euvolemic, usually shortly before
discharge. Particular caution is indicated in patients who have required
inotropes during their hospitalization.
 A small randomized trial and a larger observational study found that initiation of
therapy prior to hospital discharge in stable patients improves long-term beta
blocker compliance without an increase in side effects or drug discontinuation,
so initiation prior to discharge is recommended in stable patients. (See "Use of
beta blockers in heart failure with reduced ejection fraction", section on 'Initiation
of therapy'.)

Ivabradine — Ivabradine reduces the risk of hospitalization in patients with chronic

HFrEF but has no proven role in acute HF.

●For patients who are already taking ivabradine, management depends upon
the severity of HF decompensation, heart rate, and hemodynamic instability. If
an increased heart rate appears necessary to maintain cardiac output, then we
suggest holding ivabradine in patients with severe decompensation.

●For patients who are not already taking ivabradine, we suggest that this agent
not be initiated at the time of presentation with an episode of ADHF or with initial
oral therapy that generally includes an angiotensin inhibitor and then a beta
blocker. We suggest ivabradine for patients with chronic HFrEF (with left
ventricular ejection fraction [LVEF] ≤35 percent) in sinus rhythm with a resting
heart rate ≥70 beats per minute (bpm) and who are either on a maximum
tolerated dose of beta blocker or have contraindication to beta blocker use.
Concurrent treatment should include ACE inhibitor (or ARB), and a
mineralocorticoid receptor blocker (if potassium can be appropriately
monitored). (See "Use of ivabradine in heart failure with reduced ejection
fraction", section on 'Selection of candidates for ivabradine therapy'.)

Mineralocorticoid receptor antagonist — In patients already taking an MRA, such

therapy can generally be continued during an episode of acute decompensation, with
appropriate monitoring of blood pressure, renal function, and electrolytes. For
patients not taking an MRA who have an indication for therapy, we favor initiation
prior to or soon after discharge (as needed to allow careful monitoring of serum
potassium levels). In patients in whom an ACE inhibitor or ARB was started or
uptitrated shortly prior to discharge, it is recommended that MRA initiation be delayed
until the first outpatient visit and evaluation of potassium.

Randomized trials have demonstrated that MRA therapy

(spironolactone or eplerenone) reduces mortality when included in long-term
management of selected patients with systolic HF who can be carefully monitored for
serum potassium and renal function. These include patients who have New York
Heart Association (NYHA) functional class II HF and an LVEF ≤30 percent; or NYHA
functional class III to IV HF and an LVEF ≤35 percent; and patients post-ST elevation
MI who are already receiving therapeutic doses of ACE inhibitor, have an LVEF ≤40
percent, and have either symptomatic HF or diabetes mellitus. The serum potassium
should be <5.0 meq/L and estimated glomerular filtration rate should be
≥30 mL/min per 1.73 m2. (See "Use of mineralocorticoid receptor antagonists in heart
failure with reduced ejection fraction", section on 'Our approach'.)
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 includes supplemental oxygen and assisted ventilation if

necessary and a loop diuretic for volume overload (table 1).

•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 acute respiratory failure in adults", section
on 'Cardiogenic pulmonary edema'.)

•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 mechanical
ventilation".)

•In patients with ADHF and fluid overload, we recommend that initial
therapy include a loop diuretic (administered intravenously) (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.)

●Vasodilators may be required to correct elevated filling pressures and/or LV

afterload in patients with ADHF. Indications for vasodilator therapy with close
hemodynamic monitoring in the setting of ADHF include the following
(see 'Approach to vasodilator therapy' above):
 •For patients with urgent need for afterload reduction (eg, 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".)

•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'.)

•We suggest vasodilator therapy as a component of therapy for patients

with refractory HF and low cardiac output (Grade 2C). (See "Management
of refractory heart failure with reduced ejection fraction", section on
'Approach to low cardiac output'.)

●For most patients hospitalized with ADHF, we recommend against treating

with nesiritide (Grade 1A). In carefully selected patients with appropriate
hemodynamics (including absence of hypotension or cardiogenic shock) who
remain symptomatic despite routine therapy, a trial of nesiritide may be helpful
as an alternative to other vasodilator therapy (nitroglycerin or nitroprusside).
Nesiritide has a longer effective half-life than nitroglycerin or nitroprusside, so
side effects such as hypotension may persist longer. (See "Nesiritide in the
treatment of acute decompensated heart failure", section on
'Use' and 'Nesiritide'above.)

●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 left
ventricular outflow obstruction are treated with beta blocker therapy and gentle
hydration if pulmonary edema is not present. (See 'Approach to
hypotension' above.)

●In patients with HFpEF, long-term therapy is based largely on associated

conditions (eg, hypertension or edema) since trial data are limited with no
established survival benefit from any specific therapy. Management of chronic
medications (such an antihypertensive agents) during an ADHF episode
depends upon the patient’s hemodynamic condition. (See 'Approach to long-
term therapy for heart failure with preserved ejection fraction' above
and "Treatment and prognosis of heart failure with preserved ejection fraction".)

●In patients with chronic HFrEF, the long-term use of angiotensin inhibitor
(angiotensin converting enzyme inhibitor, angiotensin II receptor blocker, or
angiotensin receptor-neprilysin inhibitor), beta blockers, and mineralocorticoid
receptor antagonist reduces mortality. Management of these agents during an
ADHF episode depends upon whether the patient was already taking these
medications and the patient’s hemodynamic condition during the acute episode.
 (See 'Approach to long-term therapy for heart failure with reduced ejection
fraction' above and "Overview of the therapy of heart failure with reduced
ejection fraction".)

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