Acute Heart Failure: Evaluation and Management

DynaMed Plus: Acute heart failure 2017-12-20, 10(11 PM
Acute heart failure

Overview and Recommendations
Background
Patients with acute heart failure have newly diagnosed heart failure or decompensation of chronic heart
failure.
Two major types of heart failure are heart failure with reduced ejection fraction or heart failure with
preserved ejection fraction.
Symptoms are due to hemodynamic abnormalities resulting in congestion (most common presentation)
and/or low cardiac output.
Complications of heart failure, particularly acute heart failure, include respiratory and/or renal failure.
Evaluation
Suspect heart failure in patients with symptoms including dyspnea and/or fatigue, and findings on exam
including jugular venous distension, hypotension, S3 heart sound, rales, and edema, leading to
unscheduled medical care or hospital admission.
Identify potential precipitating factors for acute heart failure including new or worsened left ventricular
dysfunction, noncompliance with medications and/or diet, volume overload, drug exposure,
arrhythmia, valvular disease, and/or uncontrolled hypertension (Strong recommendation).
Obtain initial testing including cardiac troponin testing, complete blood count, serum chemistries,
fasting lipid profile, liver function tests, and thyroid-stimulating hormone to identify precipitating and
complicating factors and to guide treatment (Strong recommendation).
Obtain B-type natriuretic peptide (BNP) or N-terminal pro-B-type natriuretic peptide (NT-proBNP)
level, especially if diagnosis is uncertain (Strong recommendation).
Higher levels increase the likelihood of a diagnosis of heart failure but may be elevated due to
other causes.
Obtain 12-lead electrocardiogram (ECG) to evaluate for possible acute coronary syndrome as a
potential cause of heart failure (Strong recommendation) or other causes of heart failure such as
arrhythmia.
Obtain a chest x-ray to evaluate for the presence of pulmonary edema, heart size, and detect underlying
lung disease as a possible noncardiac cause of symptoms (Strong recommendation).
Use transthoracic echocardiography to assess left and right ventricular systolic function, valve function,
left atrial size, identify other structural abnormalities, and to evaluate parameters of diastolic function
(Strong recommendation).
Consider radionuclide ventriculography to assess left ventricular ejection fraction and volume
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when transthoracic echocardiography is inadequate (Weak recommendation).

Differential diagnosis includes other causes of dyspnea such as asthma, COPD, pulmonary infections,
and pulmonary embolism
Management
Administer oxygen in patients with capillary oxygen saturation < 90% or partial pressure of oxygen in
arterial blood (PaO2) < 60 mm Hg (8 kilopascals [kPa]) (Strong recommendation).
Administer IV loop diuretics (such as furosemide 40-100 mg; initial IV dose should equal or exceed
chronic oral daily dose, given as intermittent bolus or continuous infusion) to treat symptoms of fluid
overload (Strong recommendation).
Use invasive hemodynamic monitoring with pulmonary artery catheter to guide therapy in patients
with suspected heart failure in whom fluid status cannot be determined from clinical assessment
(Strong recommendation)
For patients requiring additional measures to promote diuresis
Consider adding low-dose dopamine infusion to loop diuretic to promote diuresis and preserve
renal function and renal blood flow (Weak recommendation).
Consider ultrafiltration (Weak recommendation), though comparisons with diuresis have
inconsistent results including increased risk for serious adverse events.
For patients that have significant dyspnea despite supplemental oxygen and aggressive diuresis
Consider vasodilators (IV nitroglycerin, nitroprusside, or nesiritide) as adjunct to diuretics to
relieve dyspnea in absence of symptomatic hypotension (Weak recommendation).
Consider noninvasive positive pressure ventilation (Weak recommendation).
Consider IV opiates (for example, morphine sulfate ) in particularly distressed, anxious, or
restless patients to relieve symptoms and improve breathlessness (Weak recommendation).
For patients with borderline or low blood pressure with documented severe systolic dysfunction
Consider short-term, continuous IV inotropic support (such as dopamine, dobutamine, or
milrinone) (Weak recommendation).
See cardiogenic shock for management of patients who require inotropic support due to persistent
hypotension and/or reduced cardiac output.
Give venous thromboembolism prophylaxis with unfractionated heparin, low-molecular-weight
heparin, or fondaparinux for those patients being hospitalized unless risk for bleeding outweighs likely
benefits (Strong recommendation). Consider IMPROVE Combined Risk Calculator to predict in-
hospital risks.
Continue oral beta blockers and angiotensin-converting enzyme (ACE) inhibitors (or an angiotensin
receptor blocker [ARB]), or initiate after optimization of volume status and before hospital discharge
unless hemodynamically unstable (Strong recommendation).
Related Summaries
Heart failure (list of topics)
Heart failure with reduced ejection fraction (HFrEF) for information on chronic heart failure
Heart failure with preserved ejection fraction (HFpEF)
Heart failure screening and prevention
Natriuretic peptide and biomarkers testing for heart failure
Medicare/Joint Commission National Hospital Inpatient Quality Measures
General Information
Description
new or worsened symptoms of heart failure (dyspnea, fatigue, or edema) leading to unscheduled
medical care or hospital admission(1)
most commonly presents as exacerbation of symptoms in patients with established heart failure (HFrEF
or HFpEF) after a period of relative stability(1)
Also called
acute decompensated heart failure

acute heart failure syndrome
cardiogenic pulmonary edema
acute cardiogenic pulmonary edema
congestive heart failure
Definitions
Acute heart failure can either represent the first presentation of heart failure or decompensated heart
failure for patients with known underlying heart failure
American College of Cardiology Foundation/American Heart Association (ACCF/AHA) definitions of
heart failure classification(6)
heart failure with reduced ejection fraction (HFrEF)
ejection fraction ≤ 40%
also called systolic heart failure
most randomized trial evidence is specific to patients with HFrEF
heart failure with preserved ejection fraction (HFpEF)
typically ejection fraction ≥ 50%
also called diastolic heart failure
important to consider and exclude other potential noncardiac causes of symptoms
suggestive of heart failure
beyond symptom management with diuresis, and management of known predisposing
risks and comorbid conditions, no specific therapies yet proven to reduce mortality
subsets of HFpEF include
HFpEF, borderline
ejection fraction 41%-49%
intermediate group with characteristics, treatment patterns, and outcomes
similar to patients with HFrEF
treated according to guidelines for HFrEF
HFpEF, improved
ejection fraction > 40%
previously had HFrEF
treated according to guidelines for HFrEF
Types
American College of Cardiology Foundation/American Heart Association (ACCF/AHA) staging of

development of heart failure
ACCF/AHA Staging of Heart Failure:

At high risk for heart failure but without structural heart disease or symptoms of
Stage A
heart failure
Stage B Structural heart disease but without signs or symptoms of heart failure
Stage C Structural heart disease with prior or current symptoms of heart failure
Stage D Refractory heart failure requiring specialized interventions
Abbreviation: ACCF/AHA, American College of Cardiology/Foundation/American Heart
Association.
Reference - Circulation 2013 Oct 15;128(16):e240 PDF
New York Heart Association (NYHA) functional classification
NYHA Functional Classification:

NYHA Class Patient Symptoms
No limitation of physical activity
Ordinary physical activity does not cause
Class I (mild)
symptoms of heart failure (undue fatigue,
palpitations, and dyspnea)
Slight limitation of physical activity
Class II (mild) Comfortable at rest, but ordinary physical
activity results in symptoms of heart failure
Significant limitation of physical activity
Class III (moderate) Comfortable at rest, but less than ordinary
activity causes symptoms of heart failure
Unable to carry out any physical activity
Class IV (severe) without symptoms of heart failure or
symptoms of heart failure at rest
Abbreviation: NYHA, New York Heart Association.
Reference - Circulation 2013 Oct 15;128(16):e240 PDF
Epidemiology
Who is most affected
adults
children with heart failure have different comorbidities than adults in retrospective study of 5,610
children and 732,752 adults admitted with heart failure
compared to adults, children had higher rates of cardiac procedures (61.4% vs. 0.3%, p < 0.01)
and congenital heart disease (61% vs. 0.3%, p < 0.01)
Reference - BMC Cardiovasc Disord 2006 May 25;6:23 full-text
Incidence/Prevalence
acute decompensated heart failure is leading cause for hospital admission among patients > 65 years
old in Western countries(1)
in United States
primary diagnosis of heart failure in about 1 million hospital admissions per year
hospital admissions due to acute decompensated heart failure have tripled in last 30 years
Reference - Circulation 2012 Jan 3;125(1):e2
incidence and prevalence increases with age(6, 7)
age-adjusted incidence rate of heart failure hospitalization in United States appears higher in
African-Americans compared to Caucasians
based on retrospective record review
1,282 patients with incident heart failure hospitalizations or deaths in 4 United States
communities from 1987 to 2002 included
3.4 per 1,000 person-years for Caucasian women
6 per 1,000 person-years for Caucasian men
8.1 per 1,000 person-years for African-American women
9.1 per 1,000 person-years for African-American men
Reference - Am J Cardiol 2008 Apr 1;101(7):1016
age-adjusted incidence rate of first hospitalization for heart failure in Scotland
based on population study of 5.1 million people from 1986 to 2003
116,556 people (2.3%) had first hospital discharge for heart failure
Rate of First Hospitalization for Heart Failure:
1986 1994 2003
105 per
Men 124 per 100,000 162 per 100,000
100,000
101 per
Women 128 per 100,000 160 per 100,000
100,000
Reference - Circulation 2009 Feb 3;119(4):515
Likely risk factors

for risk factors for developing heart failure see Heart failure with reduced ejection fraction. risk factors
for developing acute heart failure are often similar for patients with HFrEF.
Possible risk factors

nonsteroidal anti-inflammatory drugs (NSAIDs)

prior heart failure diagnosis and use of nonsteroidal anti-inflammatory drugs (NSAIDs)
associated with higher risk for first hospitalization for heart failure
based on case-control study
1,396 patients with first hospital admission for nonfatal heart failure were compared to
5,000 controls (matched for age, sex, and calendar year)
greatest independent risk factor was prior clinical heart failure diagnosis (relative risk [RR]
7.3, 95% CI 6.1-8.8)
compared to patients not taking current NSAID, first hospitalization for heart failure
associated with
current NSAID use (adjusted RR 1.3, 95% CI 1.1-1.6)
current NSAID use with prior heart failure diagnosis (adjusted RR 8.6, 95% CI 5.3-
13.8)
Reference - Heart 2006 Nov;92(11):1610 full-text
current NSAID use associated with increased risk of hospital admission for heart failure
compared to past use
based on nested case control study
about 10 million new nonsteroidal anti-inflammatory drug (NSAID) users between 1999
and 2010 in Italy, Germany, United Kingdom, and the Netherlands were assessed
92,163 patients (mean age 76 years) admitted to hospital for heart failure were matched by
age, gender, and year of cohort entry to 8,246,403 controls
9.1% of cases and 2.5% of controls had history of heart failure diagnosis in the year prior
to starting NSAID treatment
current use of any NSAID (in previous 14 days) associated with increased risk of hospital
admission for heart failure compared to past use (> 183 days) (adjusted odds ratio 1.19,
95% CI 1.17-1.22)
consistent results for diclofenac, ibuprofen, indomethacin, ketorolac, naproxen,
nimesulide, piroxicam, etoricoxib, and rofecoxib
results were consistent regardless of history of heart failure or gender
association was dose dependent for diclofenac, etoricoxib, indomethacin, naproxen,
and rofecoxib (p < 0.005 for each)
Reference - BMJ 2016 Sep 28;354:i4857 full-text
NSAIDs appear to be associated with increased risk for relapse of heart failure, but not
associated with new onset of heart failure
based on cohort study
7,277 patients in Rotterdam study from 1991-1998 were evaluated
345 patients had incident heart failure during follow-up
among patients with prevalent heart failure, ≥ 1 prescription for NSAID since diagnosis of
heart failure associated with increased risk for heart failure relapse (adjusted relative risk
9.9, 95% CI 1.7-57)
current use of NSAIDs not associated with risk of incident heart failure
Reference - Arch Intern Med 2002 Feb 11;162(3):265
rofecoxib and possibly nonselective NSAIDs, but not celecoxib associated with increased
risk of hospitalizations for heart failure
based on retrospective cohort study
138,882 NSAID-naive patients > 66 years old who were started on rofecoxib (14,583
patients), celecoxib (18,908 patients), nonselective NSAIDs (5,391 patients), and 100,000
randomly selected non-NSAID users were evaluated

compared to non-NSAID users, increased risk of admission for heart failure in patients
taking rofecoxib (adjusted relative risk 1.8, 95% CI 1.5-2.2)
adjusted relative risk for heart failure admission compared to non-NSAID users was 1.8
for rofecoxib (95% CI 1.5-2.2), 1.4 for nonselective NSAID users (95% CI 1-1.9) and 1
for celecoxib users (95% CI 0.8-1.3)
study not funded by pharmaceutical industry
Reference - Lancet 2004 May 29;363(9423):1751, correction in Lancet 2004 Oct
2;364(9441):1218, commentary can be found in Lancet 2004 Oct 23;364(9444):1486,
summary can be found in Am Fam Physician 2005 Feb 15;71(4):790
glitazones associated with heart failure

BOXED WARNINGS include risk of heart failure for thiazolidinedione (glitazone) drug class
(level 2 [mid-level] evidence), and possible association with increased risk of myocardial
ischemic events with rosiglitazone (level 2 [mid-level] evidence)
rosiglitazone associated with increased risk of myocardial infarction, heart failure and death
compared with pioglitazone in patients > 54 years old with type 2 diabetes (level 2 [mid-level]
evidence)
see Glitazones for details
medications which may worsen heart failure include

anti-inflammatory medications - corticosteroids (case series), nonsteroidal anti-inflammatory
drugs (NSAIDs) (case series)
cardiovascular medications - class I and III antiarrhythmics (excluding amiodarone and
dofetilide; randomized trials), calcium channel blockers (randomized trials), minoxidil
(randomized trial)
diabetes medications - metformin (case series), thiazolidinediones (glitazones) (open-label trial),
dipeptidyl peptidase IV (DPP-4) inhibitors (gliptins)
hematologic medications - anagrelide (randomized trial), cilostazol (randomized trial)
neuropsychiatric medications - amphetamines (randomized trial), carbamazepine (anecdotal),
clozapine (case series), ergot alkaloids (case reports), pergolide (case reports), tricyclic
antidepressants (case reports)
miscellaneous - beta-2 agonists (case series), itraconazole (case series), licorice (open-label trial)
References - Arch Intern Med 2004 Apr 12;164(7):709, correction can be found in Arch Intern
Med 2004 Jul 12;164(13):1464, commentary can be found in Arch Intern Med 2005 Jan
10;165(1):118 , FDA Press Release 2016 Apr 5
medications associated with heart failure
itraconazole associated with 58 cases of heart failure (Lancet 2001 Jun 2;357(9270):1766)
FDA warns that use of DPP-4 inhibitors saxagliptin or alogliptin may be associated with
increased risk for heart failure, particularly in patients with preexisting heart or kidney disease
(FDA Press Release 2016 Apr 5)
trastuzumab - boxed warning includes risk for clinical and subclinical cardiac failure; incidence
highest in patients receiving concomitant anthracycline-containing chemotherapy regimens (FDA
DailyMed Mar 2016)
TNF inhibitors may be associated with new or worsening heart failure, but evidence inconsistent
(Biologic disease-modifying antirheumatic drugs (DMARDs) for rheumatoid arthritis for details)
for additional guidance on medications which may worsen or cause heart failure, see American Heart
Association (AHA) Scientific Statement on drugs that may cause or exacerbate heart failure
(Circulation 2016 Aug 9;134(6):e32 full text)
fine particulate air pollution associated with hospital admission rate

based on retrospective record review
daily time-series data collected 1999-2002 from 204 urban counties in United States with 11.5
Medicare enrollees living mean 6 miles from monitor for particulate matter 2.5 micrometers or
smaller in diameter
rate of hospital admissions for heart failure increased by 1.28% for every 10 mcg/m3 increase in
particles 2.5 micrometers or less
Reference - JAMA 2006 Mar 8;295(10):1127, commentary can be found in JAMA 2006 Oct
25;296(16):1966
placement of waist-high, custom-fit compression stockings temporally related to acute pulmonary
edema in case report of 75-year-old man 1 day after carotid endarterectomy, presumably due to fluid
shift overcoming cardiac reserve (Mayo Clin Proc 1999 May;74(5):478), commentary can be found in
Mayo Clin Proc 1999 Sep;74(9):946
Etiology and Pathogenesis

Causes of acute heart failure
left ventricular dysfunction(1)

acute myocarditis or progressive cardiomyopathy (with remodeling)
ischemic heart disease
acute myocardial infarction
tachyarrhythmia (such as atrial fibrillation or ventricular tachycardia)
bradyarrhythmia
stenotic or regurgitant valvular disease
constrictive pericarditis or acute tamponade
uncontrolled hypertension, hypertensive urgency or emergency(1, 7)
volume overload due to
excess dietary sodium(1, 7)
excess dietary fluid(6)
hepatic dysfunction(1)
renal insufficiency or bilateral renovascular disease may lead to fluid retention (BMJ 2003 Mar
1;326(7387):489 full-text)
high output state with increased metabolic demands(1)
intracardiac or extracardiac shunt
anemia
septicemia
inflammation or infection
thyroid disease
major surgery
pregnancy(7)
Paget's disease(7)
arteriovenous fistula(7)
review of high output heart failure can be found in QJM 2009 Apr;102(4):235 full-text
hormonal disturbances(7)
diabetic ketoacidosis (DKA)
adrenal insufficiency
pregnancy and peripartum related abnormalities
medication-related
noncompliance with heart failure medications such as diuretics or angiotensin-converting
enzyme (ACE) inhibitors(1, 7)
excess beta blockade(1)
cardiotoxic drugs (for example, daunorubicin)
nonsteroidal anti-inflammatory drugs (NSAIDs)(7)
corticosteroids(7)
negative inotropic agents(7)
review of drug-induced heart failure can be found in J Am Coll Cardiol 1999 Apr;33(5):1141
substance abuse (alcohol or stimulants)(1, 7)
infection (such as pneumonia, infective endocarditis, or sepsis)(7)
surgery and perioperative complications(7)
pulmonary-related(7)
acute exacerbation of chronic obstructive pulmonary disease (COPD)
pulmonary embolism (PE)
cerebrovascular injury(7)
acute mechanical-related(7)
complications of myocardial infarction (such as free wall rupture ,ventricular septal defect, and
acute mitral regurgitation)
chest trauma or cardiac intervention
acute dysfunction of heart valve (native or prosthetic) secondary to endocarditis, aortic
dissection, or thrombosis
causes for exacerbation of heart failure in prospective cohort study
768 patients with ejection fraction < 40% participating in 2 randomized trials over 43 weeks
evaluated
risk factors associated with worsening of heart failure status included
noncompliance with salt restriction (22% episodes)
other noncardiac causes (20%, especially pulmonary infectious processes)
use of antiarrhythmic agents in prior 48 hours (15%)
arrhythmias (13%)
calcium channel blockers (13%)
inappropriate reductions in heart failure therapy (10%)
factors commonly associated with worsening heart failure in other studies were not associated
with worsening heart failure in this patient population, including
medication noncompliance
myocardial ischemia
uncontrolled hypertension
arrhythmia
Reference - Arch Intern Med 2001 Oct 22;161(19):2337 full-text
Pathogenesis
new acute or exacerbation of chronic heart failure may be due to
hemodynamic dysregulation
volume overload conditions (for example, valvular regurgitation) may lead to increased
end-diastolic pressure and reduced systolic function
various conditions may affect contractility (for example, myocardial infarction, primary
myopathy) which may cause both pressure and volume overload
reduced cardiac output may result in dyspnea or edema
neurohormonal dysregulation
acutely reduced cardiac output leads to baroreceptor-mediated sympathetic activation,
causing increased heart rate, blood pressure, and vasoconstriction
this response acutely compensates for reduced cardiac output, then leads to myocardial
beta-receptor downregulation and decrease of myocardial contractility from normal stimuli
activation of renin-angiotensin-aldosterone system occurs with increased adrenergic tone
resulting increased production of angiotensin II causes stimulation of adrenal glands,
which
releases additional catecholamines which cause juxtaglomerular apparatus in kidney
to release renin, which in turn increases vascular tone and may cause pressure
overload on heart
releases aldosterone
elevated aldosterone levels and nonosmotic release of vasopressin decrease renal excretion
of sodium and water, which may lead to increased preload, edema, and dyspnea
Reference - Cardiol Clin 2014 Feb;32(1):9
most acute heart failure syndrome hospitalizations are caused due to volume overload than by low
cardiac output (Am J Med 2006 Dec;119(12 Suppl 1):S3)
elevated left ventricular filling pressures indicating hemodynamic congestion may be present for days
or weeks before presentation with clinical congestion, characterized by systemic and pulmonary
congestion which may result in hospital admission (Am J Med 2006 Dec;119(12 Suppl 1):S3)
see Heart failure with preserved ejection fraction for pathophysiology of diastolic dysfunction
see Cardiogenic shock for pathophysiology of cardiogenic shock
History and Physical

History
Chief concern (CC)
common signs and symptoms include(1, 3)

paroxysmal nocturnal dyspnea
orthopnea
dyspnea on exertion
fatigue and weight gain

cough
exercise intolerance
increasing abdominal girth
lower extremity edema
shortness of breath when bending forward ("bendopnea") (JACC Heart Fail 2014 Feb;2(1):24)
presenting symptoms may vary in severity, from worsening of peripheral edema to life-threatening
pulmonary edema or cardiogenic shock(1, 6, 7)
History of present illness (HPI)
patients with acute heart failure may present with new or worsening(1, 3, 5, 6)
dyspnea and fatigue, which may limit exercise tolerance
symptoms of peripheral and/or pulmonary edema due to fluid retention
onset of signs and symptoms vary(7)
may develop over weeks or months (for example, increasing breathlessness or edema due to
various causes)
may develop over minutes to hours if cause is an acute event (for example, in patients with acute
myocardial infarction, myocardial ischemia, arrhythmia such as atrial fibrillation)
ask about(5, 6)
severity and precipitants of symptoms
recent changes in dose, discontinuation of, or new medications for heart failure
dietary changes
presence of the following
chest pain
lightheadedness
palpitations
syncope
symptoms may rapidly improve with treatment (for example, dyspnea improvement following diuresis
in patients with pulmonary edema)(5, 6, 7)
additional information regarding presentation of acute heart failure
elevated systolic blood pressure (BP) in > 50%, with signs and symptoms typically developing
abruptly, with predominantly pulmonary vs. systemic congestion
normal systolic BP in > 40% with gradual development of signs and symptoms over days to
weeks, with significant systemic congestion
systolic BP < 90 mm Hg in < 8%, typically with signs of organ hypoperfusion and low cardiac
output
pulmonary edema in < 3% with rapid or gradual onset
cardiogenic shock in < 1% with rapid onset, typically complication of acute myocardial
infarction or fulminant myocarditis
"flash" pulmonary edema (incidence unclear) with abrupt onset due to severe systemic
hypertension
isolated heart failure, acute coronary syndromes, and post cardiac surgery heart failure (incidence
unclear) typicall have rapid or gradual onset
Reference - Circulation 2005 Dec 20;112(25):3958 full text
weight gain in prior week (in patients with heart failure) associated with hospitalization for
heart failure
based on nested case-control study
among 268 heart failure patients referred to home monitoring system, 134 patients hospitalized
for heart failure were matched to 134 patients not hospitalized for heart failure
compared to weight gain ≤ 2 lbs (0.91 kg) within prior week, risk for heart failure hospitalization
was higher with weight gain of
2-5 lbs (0.91-2.27 kg) (adjusted odds ratio [OR] 2.77, 95% CI 1.13-6.8)
5-10 lbs (2.27-4.54 kg) (adjusted OR 4.46, 95% CI 1.45-13.75)
> 10 lbs (4.54 kg) (adjusted OR 7.65, 95% CI 2.22-26.39)
Reference - Circulation 2007 Oct 2;116(14):1549
Medication history
ask about use of medications that may be causes or risk factors, including
cardiotoxic chemotherapy (for example, anthracyclines)(5, 6)
trastuzumab(6)
amphetamines/stimulants(1, 6)
negative inotropic drugs (for example, verapamil)(7)
medications that increase salt and fluid retention (for example, corticosteroids)(7)
ask about previous or current diuretic use
see possible risk factors for list of additional medications
Past medical history (PMH)
ask about conditions that may be causes or risk factors, including(3, 6)

known history of heart failure
myocardial infarction
coronary artery disease
dyslipidemia
diabetes mellitus
hypertension
chronic obstructive pulmonary disease (COPD) or other lung disease
cardiac valve dirsease
pulmonary embolism or pulmonary hypertension
sleep apnea
infection
recent surgery or trauma
ask about previous echocardiogram or cardiac catheterization and indication for test
Family history (FH)
ask about family history of(6)

sudden death
dilated cardiomyopathy
hypertrophic cardiomyopathy
syncope
pacemaker use
Social history (SH)
ask about potential causes or risk factors, including

significant smoking history(1, 3, 4, 5)
heavy alcohol consumption(1, 5, 6)
stimulants/amphetamine use(1, 6)
Physical
General physical
potential indicators of heart failure with reduced ejection fraction (systolic dysfunction)(4)
tachycardia (pulse > 90-100 beats/minute)
systolic blood pressure < 90 mm Hg
proportional pulse pressure < 33%
proportional pulse pressure = (systolic blood pressure - diastolic blood pressure)/systolic
blood pressure
proportional pulse pressure < 25% may indicate reduced cardiac index
potential indicators of heart failure with preserved ejection fraction (diastolic heart failure)(4)
diastolic blood pressure > 105 mm Hg
overall blood pressure ≥ 160/100 mm Hg
checking for orthostatic changes (supine and upright) in blood pressure and pulse may identify volume
depletion or excessive vasodilation(6)
check for low perfusion at rest (cold vs. warm) with narrow pulse pressure, cool extremities,
hypotension(6)
check peripheral pulses
pulsus alternans (alternating strong and weak palpable arterial pulses as a result of alternating left
ventricular stroke volumes) may be present with severe left ventricular dysfunction (J Am Soc
Echocardiogr 2007 Jul;20(7):905.e5)
elderly patients often present without typical findings (J Am Geriatr Soc 1997 Sep;45(9):1128),
commentary can be found in J Am Geriatr Soc 1998 Aug;46(8):1053
Blood pressure and pulse response to Valsalva maneuver
blood pressure response to Valsalva maneuver

procedure(3)
inflate and lock pressure cuff to 15 mm Hg above resting supine systolic blood pressure
(SBP) and Korotkoff sounds should not be audible at this point
patient performs sustained exhalation against closed glottis for ≥ 10 seconds (Valsalva)
normal response(3)
SBP rises 30-40 mm Hg above baseline for 1-3 seconds and Korotkoff sounds appear
(Phase 1)
SBP drops below baseline as venous return decreases and Korotkoff sounds disappear
(Phase 2)
when Valsalva is released (patient inhales) there is further drop in SBP with Korotkoff
sounds still absent (Phase 3)
SBP rises ≥ 15 mm Hg above baseline 3-15 seconds after release, Korotkoff sounds
reappear (Phase 4)
abnormalities described in heart failure(3)
phases 1-3 normal, but Korotkoff sounds do not reappear in phase 4 (absence overshoot
response)
Korotkoff sounds present in phases 2 and 3 but disappear in phase 4 (square-wave
response)
pulse response to Valsalva maneuver - during phase 2 (strain phase of maneuver)
development of tachycardia suggests normal cardiac filling pressures
no increase in heart rate suggests elevated filling pressures
Reference - J Am Soc Echocardiogr 2004 Jun;17(6):634
Skin
cyanosis or pallor may be seen in severe cases (Am Fam Physician 2012 Jun 15;85(12):1161)
Neck
jugular venous distention(3, 4, 5, 6)

elevated jugular venous pressure(1, 3, 4, 5)
jugular venous distension approximates right atrial pressure, add 5 cm to height above angle of
Louis (that is, junction of manubrium and body of sternum), normal is 6-8 cm H2O (Clinical
Methods third edition 1990 Chapter 19)
is the best indicator for identifying acute decompensated heart failure(1)
jugular venous distention has 55%-65% sensitivity and 74%-80% specificity for increased filling
pressure, based on review of 11 studies(4)
mismatch in right atrial pressure and pulmonary wedge pressure reported in 28% of 537
consecutive patients hospitalized with advanced heart failure (J Card Fail 2011 Jul;17(7):561)
may be present if tricuspid regurgitation present (Circulation 2009 May 26;119(20):2718)
anecdotal suggestion to use dorsal hand veins to estimate jugular venous pressure when jugular
venous pulses not visible (Cortlandt Forum 1997 Sep;10(9):146,115-37)
hepatojugular reflux reported to have 33% sensitivity and 94% specificity for heart failure in study of
51 patients presenting to emergency department with acute dyspnea (Chest 1990 Apr;97(4):772),
commentary can be found in BMJ 2004 Jul 24;329(7459):209 full-text
Cardiac
Palpation
normal apical impulse is located in fourth or fifth intercostal space(4)

apical impulse may be palpable in < 50% of patients but palpation with patient in 45 degrees left lateral
decubitus position or during expiration may increase yield(4)
abnormal apical impulse has 31%-36% sensitivity and 89%-95% specificity for ejection fraction <
40%, based on review of 12 studies assessing systolic dysfunction(4)
laterally displaced or enlarged point of maximal impulse suggests ventricular enlargement(6)
right ventricular heave suggests significant right ventricular dysfunction and/or pulmonary
hypertension(6)
Percussion
right parasternal area percussion may be used to estimate right ventricular and/or right atrial size
precordial percussion can be used to predict cardiomegaly on chest x-ray (Am J Med 1991
Oct;91(4):328 in ACP J Club 1992 Jan-Feb;116(1):20)
Auscultation
S3
third heart sound (S3, ventricular filling gallop)(1, 3, 6)

occurs due to left ventricular vibration with rapid early diastolic filling (elevated filling pressure or
reduced ventricular compliance)(4)
sound is low-pitched, may be faint or intermittent and should be listened for with bell of stethoscope
(usually is the only mid-diastolic heart sound)(4)
auscultation with patient in 45 degrees left lateral decubitus position increases yield(4)
S3 specific but not sensitive for acute decompensated heart failure
995 dyspneic patients > 40 years old were evaluated by acoustic cardiography
S3 on acoustic cardiography had low sensitivity (40%) but high specificity (88.5%) for
identifying acute decompensated heart failure
S3 did not predict 30-day or 90-day events
Reference - Ann Emerg Med 2009 Jun;53(6):748
S3 specific but not sensitive for left ventricular dysfunction
based on 2 cohort studies
100 patients having left-sided heart catheterization had blinded auscultation by 4 physicians
(attending, fellow, resident, and intern), phonocardiography, blood B-type natriuretic peptide
levels, echocardiography, and cardiac catheterization
S3 had low sensitivities (13%-52%) but high specificities (85%-95%) for identifying
patients with abnormal measures of left ventricular function
best test characteristics exhibited by phonocardiography and more experienced physicians
(attendings and fellows)
Reference - Arch Intern Med 2006 Mar 27;166(6):617, correction can be found in Arch
Intern Med 2006 Jun 12;166(11):1217, editorial can be found in Arch Intern Med 2006
Mar 27;166(6):603
prospective study of 90 adults undergoing nonemergent left heart catheterization

within 4 hours, patients had computerized heart sound phonocardiographic analysis for S3
and S4, cardiac catheterization for left ventricular end-diastolic pressure (LVEDP),
transthoracic echocardiography for left ventricular ejection fraction (LVEF), and blood
sampling for B-type natriuretic peptide (BNP)
S3 had
41% sensitivity and 92% specificity for LVEDP > 15 mm Hg
52% sensitivity and 87% specificity for LVEF < 50%
32% sensitivity and 92% specificity for BNP > 100 pg/mL
Reference - JAMA 2005 May 11;293(18):2238, commentary can be found in Evidence-
Based Medicine 2005 Nov-Dec;10(6):182
S4
fourth heart sound (S4, atrial gallop)(3)

S4 neither sensitive nor specific for left ventricular dysfunction
based on prospective cohort study
90 adults having nonemergent left-sided heart catheterization evaluated
within 4 hours, patients had computerized heart sound phonocardiographic analysis for S3 and
S4, cardiac catheterization for left ventricular end-diastolic pressure (LVEDP), transthoracic
echocardiography for left ventricular ejection fraction (LVEF), and blood sampling for B-type
natriuretic peptide (BNP)
S4 had
46% sensitivity and 80% specificity for LVEDP > 15 mm Hg
43% sensitivity and 72% specificity for LVEF < 50%
40% sensitivity and 78% specificity for BNP > 100 pg/mL
Reference - JAMA 2005 May 11;293(18):2238, commentary can be found in Evidence-Based
Medicine 2005 Nov-Dec;10(6):182
murmurs may suggest presence of valvular heart disease(6)
Lungs
check for congestion at rest (wet vs. dry), findings may include
wheezing(3, 5)
bibasilar rales(1, 3, 6)
check respiratory rate and for presence of pleural effusion(6)
Abdomen
hepatojugular reflux(3)
ascites(1, 5)
hepatomegaly(6)
pulsatile hepatomegaly in patients with elevated filling pressures(5)
ileus present in 14% of older heart failure patients in study of 109 patients (mean age 74 years)
admitted with heart failure compared to 3% of 114 controls admitted with hip fracture (J Am Geriatr
Soc 1999 Feb;47(2):258)
Extremities
edema (may also occur proximally in dependent areas of bed-bound patients)(1, 3)

Beau's lines - transverse nail ridging or depressions of nail plates
usually bilateral from temporary cessation of growth during severe systemic illness
picture can be found in N Engl J Med 1997 Jul 17;337(3):168
check for low perfusion at rest (cold vs. warm)(6)
Male genital exam
scrotal edema(5)
Diagnosis
Making the diagnosis
clinical suspicion based on signs and symptoms
acute decompensated heart failure unlikely unless history of heart failure or myocardial
ischemia(1)
signs and symptoms of acute decompensated heart failure often overlap with those of other
common medical conditions, no single finding is diagnostic(1)
signs and symptoms may include(5)
history
dyspnea
orthopnea
paroxysmal nocturnal dyspnea
fatigue
edema
abdominal swelling and pain
anorexia or early satiety
exam
elevated jugular venous pressure
edema or ascites
rales
wheezing
third heart sound (S3)
worsening of mitral or tricuspid regurgitation
enlarged and tender liver
hypoxia, tachypnea, or tachycardia
hepatojugular reflex
cool extremities
tests that may help confirm diagnosis include(1)

chest x-ray showing pulmonary venous congestion and interstitial edema
natriuretic peptides levels (such as B-type natriuretic peptide [BNP]) may rule out acute heart
failure or distinguish between cardiac and pulmonary causes of dyspnea
thoracic ultrasound showing B-lines (representing pulmonary congestion)
transthoracic echocardiography is diagnostic standard for identifying type of acute heart failure
systolic dysfunction based on low ejection fraction and absolute or relative impairment of
myocardial contractility
diastolic heart failure based on normal left ventricular volume and ejection fraction, and
abnormal left ventricular relaxation, filling, diastolic distensibility, or diastolic stiffness (see
Heart failure with preserved ejection fraction for further information)
Reference - Am Fam Physician 2004 Dec 1;70(11):2145
Differential diagnosis
other common causes for dyspnea include
asthma
chronic obstructive pulmonary disease (COPD)
arrhythmia
infection
interstitial lung disease
anemia
pulmonary embolism (PE)
see Dyspnea - approach to the patient for additional causes
other causes for peripheral edema
renal disease
acute renal failure
chronic kidney disease
hepatic disease
hypoproteinemia
venous insufficiency
immobility
pregnancy
endocrine disease
venous and/or lymphatic obstruction
drugs
other causes for pulmonary edema
noncardiogenic pulmonary edema (acute respiratory distress syndrome)
postobstructive pulmonary edema (Am Fam Physician 2000 Jul 15;62(2):401)
review of swimming-induced pulmonary edema: pathophysiology and risk reduction with sildenafil can
be found in Circulation 2016 Mar 8;133(10):988
Testing overview
consider common precipitating factors for acute heart failure during initial evaluation (thorough history
and physical exam), to guide appropriate therapy (ACCF/AHA Class I, Level C)(6)
electrocardiogram (ECG) and serum biomarkers, including cardiac troponin testing, recommended
promptly to identify acute coronary syndrome precipitating acute heart failure (ACCF/AHA Class I,
Level C)(6)
initial laboratory evaluation of patients presenting with acute heart failure should include (ACCF/AHA
Class I, Level C)(1, 5, 6)
serum electrolytes (including calcium and magnesium), blood urea nitrogen (BUN), serum
creatinine
random and fasting blood glucose
complete blood count
liver function tests
urinalysis
fasting lipid profile
thyroid-stimulating hormone (TSH)
blood tests useful for diagnosis of acutely decompensated heart failure, especially if diagnosis
uncertain include
B-type natriuretic peptide (BNP) (ACCF/AHA Class I, Level A; ESC Class I, Level A)
N-terminal pro-B-type natriuretic peptide (NT-proBNP) (ACCF/AHA Class I, Level A; ESC
Class I, Level A)
mid-regional pro A-type natriuretic peptide (MR-proANP) (ESC Class I, Level A)
other blood tests to consider for contributing factors or alternative diagnoses(1, 5)
troponin I
D-dimer
blood oxygenation
12-lead electrocardiogram (ACCF/AHA Class I, Level C; ESC Class I, Level C )(1, 6, 7)
chest x-ray (ACCF/AHA Class I, Level C; ESC Class I, Level C )(1, 6, 7)
transthoracic echocardiography (ACCF/AHA Class I, Level C)(1, 6)
immediate echocardiography recommended in hemodynamically unstable patients and early
echocardiography (within 48 hours) recommended in patients with unknown cardiac function or
structure (ESC Class I, Level C)(7)
consider radionuclide ventriculography to assess left ventricular ejection fraction and volume
when echocardiography is inadequate (ACCF/AHA Class IIa, Level C)
thoracic ultrasound may indicate pulmonary congestion by presence of B-lines and may use used to
rule out pneumothorax
coronary arteriography is reasonable for patients eligible for revascularization when ischemia may be
contributing to heart failure (ACCF/AHA Class IIa, Level C)
consider screening for other conditions in selected patients (ACCF/AHA Class IIa, Level C), including
hemochromatosis
HIV infection
rheumatologic diseases
amyloidosis
pheochromocytoma
Blood tests
Recommendations for blood tests
American College of Cardiology Foundation/American Heart Association (ACCF/AHA)

recommendations for testing(6)
initial recommended testing of patients presenting with heart failure includes blood tests for
(ACCF/AHA Class I, Level C)
serum electrolytes, calcium, magnesium
blood urea nitrogen (BUN), serum creatinine
glucose
fasting lipid profile
in patients with dyspnea, measurement of B-type natriuretic peptide (BNP) or N-terminal pro-B-
type natriuretic peptide (NT-proBNP) useful to support making diagnosis of heart failure,
especially if clinical uncertainty (ACCF/AHA Class I, Level A)
consider screening for other conditions in selected patients (ACCF/AHA Class IIa, Level C),
including
hemochromatosis
HIV infection
rheumatologic diseases
amyloidosis
pheochromocytoma
European Society of Cardiology recommendations for blood testing in patients with suspected acute
heart failure(7)
natriuretic peptide level measurement recommended in patients with acute dyspnea and
suspected acute heart failure to differentiate between cardiac and noncardiac causes of acute
dyspnea, such as any (ESC Class I, Level A)
brain natriuretic peptide (BNP) levels
N-terminal pro-B type natriuretic peptide (NT-proBNP) levels
mid-regional pro A-type natriuretic peptide (MR-proANP) levels
initial recommended testing of patients presenting with acute heart failure includes blood tests
for (ESC Class I, Level C)
cardiac troponin
blood urea nitrogen (BUN) (or urea)
creatinine
electrolytes (sodium and potassium)
glucose
Brain natriuretic peptide (BNP) testing
in patients presenting with acute dyspnea

B-type natriuretic peptide (BNP) or N-terminal pro-B-type natriuretic peptide (NT-proBNP)
levels useful for diagnosis of heart failure, especially if clinical uncertainty (ACCF/AHA Class I,
Level A) and for prognosis (ACCF/AHA Class I, Level A)
BNP testing appears useful for detection of heart failure in emergency department with cutoff <
100 pg/mL (< 100 ng/L) excluding heart failure and > 400 pg/mL possibly diagnosing heart
failure (level 2 [mid-level] evidence)
bedside BNP assay (Triage) appears modestly accurate for distinguishing cardiac from
noncardiac causes in patients with acute dyspnea; BNP < 50 pg/mL suggests dyspnea due to
heart failure is unlikely (level 2 [mid-level] evidence)
emergency department BNP testing may reduce hospital use in patients with acute dyspnea but
may not alter clinical outcomes in patients with severe dyspnea (level 2 [mid-level] evidence)
NT-proBNP testing appears highly sensitive for ruling out heart failure in emergency department
with cutoff < 450 pg/mL in patients aged < 50 years old, cutoff < 900 pg/mL in patients aged 50-
75 years old, and cutoff < 1,800 pg/mL in patients aged > 75 years old (level 2 [mid-level]
evidence)
elevated NT-proBNP levels associated with higher mortality in patients with acute dyspnea
rapid enzyme-linked immunosorbent assay (ELISA) for B-type natriuretic peptide (BNP) may be
more accurate than laboratory radioimmunosorbent assay (RIA) (level 2 [mid-level] evidence)
serial B-type natriuretic peptide (BNP) testing may not alter clinical outcomes in patients with
acute heart failure (level 2 [mid-level] evidence), but BNP level > 250 pg/mL at discharge
associated with higher rates of death or rehospitalization for heart failure at 6 months (level 2
[mid-level] evidence)
see Natriuretic peptide and biomarkers testing for heart failure for details
Cardiac troponin and other biomarker testing
Level C)(6)
consider other biomarkers for additional risk stratification in patients with acutely decompensated heart
failure including biomarkers of fibrosis (soluble ST2 or galectin-3) (ACCF/AHA Class IIb, Level A)(6)
myeloperoxidase levels did not predict acute decompensated heart failure in cohort of 412 patients with
acute dyspnea (Clin Chem 2009 Jan;55(1):59)
see also Natriuretic peptide and biomarkers testing for heart failure and Cardiac troponin testing for
details
Urinalysis
urinalysis recommended as part of initial laboratory evaluation of patients presenting with heart failure
(ACCF/AHA Class I, Level C)(6)
Imaging studies
Chest x-ray
patients with suspected or new-onset heart failure, or presenting with acute decompensated heart
failure, should have chest x-ray to assess (ACCF/AHA Class I, Level C)(6, 7)
heart size
pulmonary congestion (ESC Class I, Level C)

detection of alternative cardiac, pulmonary, and other diseases that may cause or contribute to
patient's symptoms (ESC Class I, Level C)
Pulmonary Edema Radiograph: This chest radiograph shows cardiomegaly and bilateral perihilar
alveolar infiltrates, consistent with a diagnosis of acute pulmonary edema due to heart failure. A
small left pleural effusion is seen, as well as fluid in the minor fissure, also consistent with heart
failure.
chest x-ray findings which may diagnose heart failure include interstitial edema and
cephalization
based on diagnostic cohort study
880 patients presenting to 7 teaching hospital emergency departments with chief complaint of
dyspnea (either sudden onset of new dyspnea or increase in severity of chronic dyspnea)
evaluated
blinded comparisons were made between chest x-ray findings, Triage brain natriuretic peptide
(BNP) test, and diagnosis made 30 days later by cardiologists (reference standard) reviewing all
available data
447 patients (51%) had final diagnosis of acute heart failure by reference standard
some chest x-ray findings could rule in heart failure due to high specificity
interstitial edema had 27% sensitivity, 98% specificity, positive likelihood ratio 12.67, and
negative likelihood ratio 0.72
cephalization had 41% sensitivity, 96% specificity, positive likelihood ratio 9.41, and
cardiomegaly had 79% sensitivity, 80% specificity, positive likelihood ratio 3.98, and
Reference - Am J Med 2004 Mar 15;116(6):363 in ACP J Club 2004 Sep-Oct;141(2):48,
summary can be found in Am Fam Physician 2004 Nov 15;80(10):2004

chest x-ray findings for prediction of heart failure in adults with acute dyspnea(3)
based on systematic review of 22 studies
likelihood ratios for chest x-ray findings
Pooled
Pooled Positive Negative
Chest X-ray Finding Number of Studies
Likelihood Ratio Likelihood
Ratio
Pulmonary venous
4 12 0.48
congestion
Interstitial edema 2 12 0.68
Alveolar edema 1 6 0.95
Cardiomegaly 6 3.3 0.33
Pleural effusions 2 3.2 0.81
findings which may suggest causes other than heart failure
Results:
Positive Likelihood Negative Likelihood
Chest X-ray Finding Number of Studies
Ratio Ratio
Pneumonia 1 0.5 1 (95% CI 1-1.1)
Hyperinflation 1 0.38 1.1 (95% CI 1-1.1)
finding of any edema (evaluated in 2 studies) not significant for positive or negative likelihood
ratios
absence of radiographic redistribution may rule out increased filling pressure
based on systematic review of 11 studies
fluid redistribution on chest x-ray had 10%-58% sensitivity and 79%-100% specificity for
increased filling pressure
Reference - JAMA 1997 Jun 4;277(21):1712
cardiothoracic ratio on chest x-ray may not accurately identify left ventricular ejection fraction
in patients with heart failure
7,476 patients with chronic heart failure evaluated
small to normal heart size consistent with diastolic dysfunction, but only weak negative
correlation found
Reference - Arch Intern Med 1998 Mar 9;158(5):501
cardiothoracic ratio did not differ between patients with normal and reduced ejection fraction
values in cohort study comparing heart failure patients (Am J Cardiol 2007 Jan 1;99(1):62)
Echocardiography
2-dimensional echocardiography with Doppler should be performed during initial evaluation of

patients presenting with heart failure to assess (ACCF/AHA Class I, Level C)(6)
ventricular function
ventricular size
ventricular wall thickness
ventricular wall motion

valve function
immediate echocardiography recommended in acute heart failure for evaluation of hemodynamically
unstable acute heart failure (ESC class I, Level C)(7)
immediate echocardiography mandatory in patients with suspected life-threatening structural or
functional cardiac abnormalities, such as any(7)
acute valvular regurgitation
mechanical complications
aortic dissection
early echocardiography (within 48 hours) recommended in acute heart failure evaluation if cardiac
function and structure unknown or may have changed since previous studies (ESC Class I, Level C)(7)
see Heart failure with preserved ejection fraction for information on echocardiography in patients with
diastolic dysfunction
repeat measurement of ejection fraction and measurement of severity of structural remodeling are
useful to provide information in patients with heart failure who (ACCF/AHA Class I, Level C)(6)
have significant change in clinical status
have experienced or recovered from clinical event
have received treatment, including guideline-directed medical therapy, that might have had
significant effect on cardiac function
may be candidates for device therapy
Doppler echocardiography may be more accurate than B-type natriuretic peptide (BNP) assay
for detecting heart failure in patients with acute dyspnea (level 2 [mid-level] evidence)
163 consecutive patients presenting to emergency department with acute, severe dyspnea had
blinded comparison of Doppler echocardiography and Triage BNP blood test
reference standard for diagnosis based on 2 cardiologists and 1 pulmonologist blinded to BNP
and Doppler results
115 (71%) patients had heart failure by reference standard
for detection of heart failure
BNP > 300 pg/mL had
sensitivity 88%
specificity 87%
positive likelihood ratio 6.77
Doppler echocardiography had
sensitivity 89%
specificity 93%
positive likelihood ratio 12.71
Reference - J Am Coll Cardiol 2002 Nov 20;40(10):1794 in ACP J Club 2003 Jul-Aug;139(1):21
restrictive pattern on emergency Doppler echocardiography may be sensitive and specific for
diagnosis of acute left ventricular heart failure in patients with acute dyspnea (level 2 [mid-level]
evidence)
based on convenience sample
145 patients with acute dyspnea had determination of Boston Clinical Criteria score for heart
failure, N-terminal prohormone brain natriuretic peptide (NT-proBNP), and emergency Doppler
echocardiography (EDecho) performed by emergency department physicians

reference standard was final diagnosis, established after reviewing all patient clinical data except
NT-proBNP and EDecho results
44% patients diagnosed with acute left ventricular heart failure by reference standard
median time needed to perform EDecho 4 minutes
Comparative Test Characteristics:
Positive Negative
Sensitivity Specificity Likelihood Likelihood
Ratio Ratio
Boston Clinical Criteria score ≥ 8 86% 51% 1.74 0.28
NT-proBNP ≥ 2,200 pg/mL 83% 70% 2.8 0.24
Left ventricular ejection fraction <
63% 76% 2.66 0.48
50%
Restrictive pattern (by analysis of
mitral flow) on EDecho (available 82% 90% 8.27 0.21
from only 125 patients)
Abbreviations: EDecho, emergency Doppler echocardiography; NT-proBNP, N-terminal
prohormone brain natriuretic peptide.
Reference - Acad Emerg Med 2010 Jan;17(1):18
B-type natriuretic peptide (BNP) testing may guide use of echocardiography in suspected heart
failure
based on systematic review and cost-effectiveness modeling
systematic review and individual patient data meta-analysis conducted for 9 studies of
symptomatic patients in primary care
optimal simplified rule derived from 1 cohort and validated in 8 other cohorts
simple clinical rule for patients with symptoms of suspected heart failure
refer directly to echocardiography if any of
history of myocardial infarction
basal lung crepitations
male with ankle edema
otherwise, check BNP test and refer for echocardiography if
BNP > 210-360 pg/mL (or NT-proBNP > 620-1,060 pg/mL) in female without ankle
edema
BNP > 130-220 pg/mL (or NT-proBNP > 390-660 pg/mL) in male without ankle
edema
BNP > 100-180 pg/mL (or NT-proBNP > 190-520 pg/mL) in female with ankle
edema
Reference - Health Technol Assess 2009 Jul;13(32):1 full-text
American College of Cardiology/American Heart Association/American Society of Echocardiography

(ACC/AHA/ASE) guideline on clinical application of echocardiography can be found in J Am Coll
Cardiol 2003 Sep 3;42(5):954 full-text, J Am Soc Echocardiogr 2003 Oct;16(10):1091, or in
Circulation 2003 Sep 2;108(9):1146 full-text
Thoracic ultrasound
consider thoracic ultrasound to confirm pulmonary congestion and pleural effusion in patients with
acute heart failure (ESC Class IIb, Level C)(7)
point-of-care lung ultrasound has high sensitivity and specificity for acute cardiogenic
pulmonary edema in patients with symptomatic acute dyspnea or clinical suspicion of congestive
heart failure (level 1 [likely reliable] evidence)
based on systematic review of diagnostic studies
systematic review of 7 studies evaluating point-of-care lung ultrasound showing B lines for
diagnosis of acute cardiogenic pulmonary edema in 1,075 patients presenting to hospital with
symptomatic acute dyspnea or with clinical suspicion of congestive heart failure
reference standard was final clinical diagnosis
performance of point-of-care lung ultrasound using B-lines for diagnosis of acute cardiogenic
pulmonary edema in analysis of all studies
sensitivity 94.1% (95% CI 81.3%-98.3%)
specificity 92.4% (95% CI 84.2%-96.4%)
positive likelihood ratio 12.4 (95% CI 5.7-26.8)
negative likelihood ratio 0.06 (95% CI 0.02-0.22)
no significant differences in overall sensitivity and specificity in subgroup analyses by study
type, patient population, and ultrasound protocol
Reference - Acad Emerg Med 2014 Aug;21(8):843, editorial can be found in Acad Emerg Med
2014 Aug;21(8):920
addition of bedside lung and cardiac ultrasound protocol to clinical exam appears to increase
specificity for detecting acute decompensated heart failure in adults presenting to emergency
department with dyspnea (level 2 [mid-level] evidence)
based on diagnostic cohort study with incomplete application of reference standard
99 patients (mean age 57 years) presenting to emergency department with dyspnea had clinical
exam and 12-view lung and cardiac ultrasound (LuCUS) protocol for heart failure assessment
initial diagnosis by treating clinician based on history, physical examination, and ECG
prior to LuCUS protocol
LuCUS performed by experienced physician sonographers
treating clinician revised diagnosis based on LuCUS results
LuCUS considered positive for acute heart failure if all of
either of ≥ 1 bilateral B-profile (≥ 3 B-lines in rib space) or any pleural effusion on lung
ultrasound
inferior vena cava maximal diameter ≥ 2 cm and < 50% collapse on cardiac ultrasound
either left ventricular ejection fraction < 45% or grade 2 or 3 diastolic dysfunction on
cardiac ultrasound
reference standard was final clinical diagnosis based on blinded chart review including lab and
imaging results, medications, and echocardiography results
unreported number of patients did not have comprehensive echocardiography or completed
echocardiography days later
LuCUS results may have been included on chart for some patients
36% had acute decompensated heart failure by reference standard
comparing performance of LuCUS protocol vs. initial clinical diagnosis for detection of acute
decompensated heart failure
sensitivity 83% vs. 94% (not significant)
specificity 83% vs. 44% (p < 0.05)

accuracy 83% vs. 63% (p < 0.05)
LuCUS protocol had positive predictive value 73% and negative predictive value 90%
Reference - Acad Emerg Med 2015 Feb;22(2):182
bedside thoracic ultrasound might predict heart failure in dyspneic adults in emergency
department (level 2 [mid-level] evidence)
based on prospective diagnostic cohort study in convenience sample without independent
validation
100 adults seeking emergency department care for shortness of breath were evaluated with 8-
zone thoracic ultrasound
positive thoracic ultrasound defined as ≥ 2 positive zones bilaterally (positive zone defined as
containing ≥ 3 B-lines)
reference standard for diagnosis of heart failure was clinical diagnosis by 2 physicians on
retrospective chart review
28% had clinical diagnosis of heart failure
for diagnosis of heart failure, positive thoracic ultrasound had
positive likelihood ratio 3.88 (95% CI 1.55-9.73)
negative likelihood ratio 0.5 (95% CI 0.3-0.82)
positive thoracic ultrasound in all 8 zones had 100% positive predictive value (but only occurred
in 9 patients)
Reference - Acad Emerg Med 2009 Mar;16(3):201
DynaMed commentary -- B-lines (also known as lung comets or comet tail artifacts) represent
hyperechoic reverberation artifacts indicative of pleural thickening and may be present when
alveoli and interstitia become edematous (such as in patients with heart failure)
Radionuclide ventriculography
radionuclide ventriculography can be performed to assess left ventricular ejection fraction and volume
when echocardiography is inadequate (ACCF/AHA Class IIa, Level C)(6)
American College of Cardiology/American Heart Association (ACC/AHA) and American Society for
Nuclear Cardiology (ASNC) guideline on use of cardiac radionuclide imaging can be found in
Circulation 2003 Sep 16;108(11):1404, summary can be found in Am Fam Physician 2004 Mar
1;69(5):1285
radionuclide ventriculography and echocardiography appear to have high correlation for assessing left
ventricular ejection fraction
radionuclide ventriculography and echocardiography have high correlation for assessment
of left ventricular ejection fraction in patients with prior myocardial infarction (level 1
[likely reliable] evidence)
based on diagnostic cohort study
86 patients (mean age 60.5 years) who had myocardial infarction 6 months prior had left
ventricular ejection fraction (LVEF) measured by radionuclide ventriculography (reference
standard) and echocardiography
significant left ventricular systolic dysfunction (LVSD) defined as LVEF < 40%
LVEF by reference standard
< 40% in 27 patients (31%)
40%-50% (borderline) in 17 patients (20%)
> 50% (normal) in 42 patients (49%)

echocardiography had high correlation with radionuclide ventriculography (correlation
coefficient 0.9) for assessment of LVEF at 6 months post myocardial infarction
for detecting significant LVSD, echocardiography had
negative predictive value 97.5%
positive predictive value 85%
Reference - Heart 2004 Dec;90(12):1422
radionuclide ventriculography and echocardiography may have good correlation for
assessment of left ventricular ejection fraction in patients with recent myocardial infarction
(level 2 [mid-level] evidence)
based on diagnostic cohort study with unclear blinding of reference standard and test under
investigation
93 patients (mean age 61 years) who had 95 episodes of myocardial infarction (MI) had
left ventricular ejection fraction (LVEF) measured by radionuclide ventriculography
(reference standard) and echocardiography at 48 hours and 10 days after MI
echocardiography had good correlation with radionuclide ventriculography (correlation
coefficient 0.82) for assessment of LVEF at 48 hours and 10 days post MI
Reference - J Am Coll Cardiol 1984 Feb;3(2 Pt 1):243
radionuclide ventriculography and echocardiography had good correlation (correlation
coefficient 0.81) for assessing left ventricular ejection fraction in 73 stable patients with various
diagnoses (8 with heart failure) (Am J Cardiol 1996 Apr 15;77(10):843)
Noninvasive imaging for myocardial ischemia and viability
noninvasive imaging to detect myocardial ischemia and viability is reasonable in patients presenting
with new-onset heart failure who have known coronary artery disease and no angina unless patient is
not eligible for revascularization (ACCF/AHA Class IIa, Level C)(6)
viability assessment is reasonable when planning revascularization in heart failure patients with
coronary artery disease (ACCF/AHA Class IIa, Level B)(6)
Coronary angiography
coronary arteriography is reasonable for patients eligible for revascularization when ischemia may be
contributing to heart failure (ACCF/AHA Class IIa, Level C)(6)
Magnetic resonance imaging
magnetic resonance imaging can be performed to assess left ventricular ejection fraction and volume
when echocardiography is inadequate (ACCF/AHA Class IIa, Level C)(6)
magnetic resonance imaging is reasonable when assessing myocardial infiltrative processes or scar
burden (ACCF/AHA Class IIa, Level B)(6)
review of cardiovascular magnetic resonance imaging can be found in CMAJ 2006 Oct
10;175(8):911 full-text
American College of Radiology (ACR) Appropriateness Criteria
American College of Radiology (ACR) Appropriateness Criteria for dyspnea: suspected cardiac origin
can be found at ACR 2010 PDF
Electrocardiography (ECG)
Level C)(6)
electrocardiogram (ECG) indicated for all patients with suspected heart failure
abnormal ECG has limited positive predictive value for heart failure, but completely normal
ECG makes heart failure with systolic function unlikely (< 10%)
common ECG abnormalities in heart failure and potential causes
sinus tachycardia - decompensated heart failure, anemia, fever, hyperthyroidism
sinus bradycardia - beta blocker, digoxin, ivabradine, verapamil, diltiazem, anti-
arrhythmic, hypothyroidism, sick sinus syndrome
atrial tachyarrhythmia - hyperthyroidism, infection, mitral valve disease, decompensated
heart failure, infarction
ventricular arrhythmia - ischemia, infarction, cardiomyopathy, myocarditis, hypokalemia,
hypomagnesemia, digitalis overdose
myocardial ischemia/infarction - coronary artery disease
atrioventricular block - infarction, drug toxicity, myocarditis, sarcoidosis, Lyme disease,
genetic cardiomyopathy (such as laminopathy, desminopathy)
Q waves - infarction, hypertrophic cardiomyopathy, left bundle branch block, preexcitation
QRS > 120 milliseconds with left bundle branch block morphology - electromechanical
dyssynchrony
left ventricular hypertrophy - hypertension, aortic valve disease, hypertrophic
cardiomyopathy
microvoltage - obesity, emphysema, pericardial effusion, amyloidosis
ambulatory ECG monitoring may be useful if
symptoms suggestive of arrhythmia or bradycardia, such as palpitations or syncope
atrial fibrillation, to monitor ventricular rate
Reference - Eur Heart J 2012 Jul;33(14):1787
possible predictors of heart failure in adults with acute dyspnea(3)
Systematic Review Results:
Pooled
Negative
ECG Finding Number of Studies Pooled Positive Likelihood Ratio
Likelihood
Ratio
Atrial fibrillation 5 3.8 0.79
New T-wave
1 3 0.83
changes
Any abnormal
2 2.2 0.64
finding
0.98
ST elevation 2 Not significant (borderline
significance)
0.95
ST depression 2 Not significant (borderline
significance)
Abbreviation: ECG, electrocardiogram.
Other diagnostic testing

most patients with acute decompensated heart failure have pulmonary capillary wedge pressure > 25
mm Hg(1)
findings on induced sputum may be associated with left ventricular dysfunction in patients with
dyspnea (level 2 [mid-level] evidence)
based on derivation cohort study without validation
46 breathless patients suspected of cardiac or respiratory disease and 9 healthy controls
underwent echocardiography followed within 72 hours by sputum induction with aerosol
hypertonic saline
Prussian blue stain performed to detect hemosiderin within macrophages which indicate
pulmonary capillary leakage
proportion of macrophages containing hemosiderin higher in 28 patients with left ventricular
dysfunction (median 17.9%) than other patients (p < 0.001)
hemosiderin-laden macrophages in induced sputum for left ventricular dysfunction had 80%
sensitivity, 94% specificity, 96% positive predictive value, and 80% negative predictive value
Reference - Lancet 1999 Sep 4;354(9181):833
Treatment
Treatment overview
General treatment of acute heart failure
high-flow oxygen recommended in patients with capillary oxygen saturation < 90% or partial pressure
of oxygen in arterial blood (PaO2) < 60 mm Hg (8 kilopascals [kPa]) (ESC Class I Level C)
fluid management
IV loop diuretics recommended if evidence of significant fluid overload (ACCF/AHA Class I,
Level B) to improve breathlessness and relieve congestion (ESC Class I, Level C)
for example, furosemide (Lasix) 40-100 mg IV bolus, double dose in 30 minutes if no
effect
increase dose or add second diuretic (for example, a thiazide) if inadequate to relieve
congestion (ACCF/AHA Class IIa, Level B)
monitor symptoms, urine output, renal function, and electrolytes during use of IV diuretics
(ESC Class I, Level C)
continuous infusion of loop diuretics appears no more effective than intermittent boluses
see Diuretics for heart failure for complete information
low-dose dopamine infusion may be considered in addition to loop diuretic therapy for
improvement of diuresis and to better preserve renal function and renal blood flow (ACCF/AHA
Class IIb, Level B)
vasodilators (IV nitroglycerin, nitroprusside, or nesiritide) may be considered as adjunct to
diuretics to relieve dyspnea in patients with acutely decompensated heart failure in absence of
symptomatic hypotension (ACCF/AHA Class IIb, Level A)
nesiritide (Natrecor) may not reduce mortality, rehospitalization, or dyspnea in patients
with acute decompensated heart failure (level 2 [mid-level] evidence) and increases risk
for hypotension
nitrates for acute heart failure syndrome have insufficient evidence for effects on clinical
outcomes
consider ultrafiltration for refractory congestion (ACCF/AHA Class IIa, Level C), but
comparisons with diuresis have inconsistent results including increased risk for serious adverse
events (level 2 [mid-level] evidence)
ventilatory support
consider noninvasive ventilation in patients with respiratory distress (respiratory rate > 25
breaths/minute, transcutaneous oxygen saturation < 90%) and start as early as possible to
improve breathlessness and reduce rate of mechanical endotracheal intubation (ESC Class IIa,
Level B)
use with caution in hypotensive patients as it may reduce blood pressure
monitor blood pressure regularly when treatment used
see Noninvasive positive pressure ventilation (NPPV) in adults for complete information
intubation recommended if unable to noninvasively manage respiratory failure leading to (ESC
Class I, Level C)
hypoxemia (partial pressure of oxygen in arterial blood < 60 mm Hg [8 kilopascal])
hypercapnia (partial pressure of carbon dioxide in arterial blood > 50 mm Hg [6.65
kilopascal])
acidosis (pH < 7.35)
IV opiates (for example, morphine) may be considered in patients with severe dyspnea and anxiety,
but nausea and hypopnea may occur (ESC Class IIb, Level B)
consider short-term, continuous IV inotropic support (such as dopamine, dobutamine, or milrinone) in
hospitalized patients with documented severe systolic dysfunction, low blood pressure, and
significantly depressed cardiac output (ACCF/AHA Class IIb, Level B)
monitor fluid intake and output, weight, serum electrolytes, blood urea nitrogen (BUN), and creatinine
daily during use of IV diuretics or active medication titration (ACCF/AHA Class I, Level C)
invasive hemodynamic monitoring
recommended to guide therapy if respiratory distress or clinical evidence of impaired perfusion
with inability to assess intracardiac filling pressures clinically (ACCF/AHA Class I, Level C)
pulmonary artery catheterization may increase adverse events (level 2 [mid-level] evidence) but
does not reduce mortality or length of hospitalization (level 1 [likely reliable] evidence)
during symptomatic exacerbation of heart failure requiring hospitalization in patients on chronic
maintenance treatment with guideline-directed medical therapy, continuation of guideline-directed
medical therapy recommended in absence of hemodynamic instability or contraindications
(ACCF/AHA Class I, Level B)(6)
see Cardiogenic shock and Acute coronary syndromes for emergency treatment in unstable patients
see Heart failure with preserved ejection fraction for treatment of patients with diastolic dysfunction
Treatment considerations after initial stabilization of acute heart failure
thromboembolism prophylaxis with unfractionated heparin, low-molecular-weight heparin, or

fondaparinux recommended unless high risk for bleeding (ACCF/AHA Class I, Level B, ACP Strong
recommendation, Moderate quality evidence, ACCP Grade 1B, level 2 [mid-level] evidence)
IMPROVE Combined Risk Calculator predicts in-hospital risks
see Deep vein thrombosis (DVT) prophylaxis for medical patients for complete information
start (or continue) oral beta blockers (ACCF/AHA Class I, Level B) after optimization of volume status
and successful discontinuation of IV diuretics, vasodilators, and inotropic agents; start at low dose and
only in stable patients
continuation of usual outpatient beta blocker regimen during hospitalization for decompensated
heart failure does not appear to worsen symptoms or increase mortality or length of hospital stay
beta blocker therapy during hospitalization for decompensated heart failure associated with
lower postdischarge mortality (level 2 [mid-level] evidence)
see Beta blockers for heart failure for complete information
start or continue angiotensin-converting enzyme (ACE) inhibitors (or angiotensin receptor blocker
[ARB]) in stable patients prior to hospital discharge (ACCF/AHA Class I, Level B)
see Angiotensin receptor blockers for heart failure for complete information
addition of aldosterone antagonist recommended in selected patients with New York Heart Association
(NYHA) class II-IV heart failure and left ventricular ejection fraction ≤ 35%, unless contraindicated, to
reduce morbidity and mortality (ACCF/AHA Class I, Level A)
see Heart failure with reduced ejection fraction for additional supportive care options.
Treatment setting
hospital-at-home care reported to be feasible in prospective study of 455 community-dwelling elderly

patients requiring hospitalization for pneumonia, heart failure exacerbation, chronic obstructive
pulmonary disease (COPD) exacerbation, or cellulitis (Ann Intern Med 2005 Dec 6;143(11):798),
editorial can be found in Ann Intern Med 2005 Dec 6;143(11):840, commentary can be found in Ann
Intern Med 2006 Mar 21;144(6):456
Treatment algorithm
European Society of Cardiology (ESC) management algorithm for patients with acute heart failure
based on clinical presentation during early phase(7)
in patients with congestion present
if perfusion adequate (also referred to as wet and warm patient)
for vascular type (fluid redistribution with hypertension predominating), options
include
vasodilator
diuretic
for cardiac type (fluid accumulation with congestion predominating), options include
diurectic
vasodilator
consider ultrafiltration if unresponsive to diuretic
if perfusion inadequate (also referred to as wet and cold patient)

if systolic blood pressure < 90 mm Hg, options include
inotropic support
consider vasopressors in refractory cases
diuretics when perfusion corrected
consider mechanical circulatory support if unresponsive to pharmacologic
therapy
if systolic blood pressure ≥ 90 mm Hg, options include
vasodilators
diuretics
consider inotropic support in refractory cases
in patients without congestion
if perfusion adequate (also referred to as dry and warm patient), adjust oral therapy
if perfusion inadequate (also referred to as dry and cold patient), consider fluid challenge
or inotropic agent if still hypoperfused after fluid challenge
see treatment overview for additional details
Fluid and electrolytes

monitor fluid intake and output, weight, serum electrolytes, blood urea nitrogen (BUN), and creatinine
daily during use of IV diuretics or active medication titration (ACCF/AHA Class I, Level C ; ESC
Class I, Level C )(6, 7)
consider fluid restriction (1.5-2 L/day) in patients with stage D heart failure, particularly in patients
with hyponatremia, to reduce congestive symptoms (ACCF/AHA Class IIa, Level C)(6)
aggressive sodium and fluid restriction does not affect weight loss or clinical stability at 3 days
compared with standard hospital diet in patients with acute decompensated heart failure (level 1
[likely reliable] evidence)
based on randomized trial
75 patients (69% male) hospitalized for ≤ 36 hours for acute decompensated heart failure with
systolic dysfunction randomized to fluid-restricted (≤ 800 mL/day) and sodium-restricted (≤ 800
mg/day) diet vs. standard hospital diet until seventh day of hospitalization or discharge if prior to
7 days
no significant difference in weight loss or clinical stability (improvement in clinical congestion
and cessation of all IV medications for heart failure) at 3-day assessment
no significant difference in hospital readmission within 30 days (29% with aggressive restriction
vs. 19% with control)
sodium- and fluid-restricted diet associated with increased perceived daily thirst (p = 0.01)
Reference - JAMA Intern Med 2013 Jun 24;173(12):1058, editorial can be found in JAMA Intern
Med 2013 Jun 24;173(12):1064
hypertonic saline plus high-dose furosemide and moderate sodium restriction may reduce
mortality and hospital readmission compared to high-dose furosemide and severe sodium
restriction for patients with advanced refractory heart failure (level 2 [mid-level] evidence)
based on 2-3 randomized trials by same authors without blinding of caregivers and confounded
treatment combinations
randomized trial with 1,771 patients
1,771 patients with refractory heart failure randomized to 1 of 2 groups
furosemide 250 mg IV plus hypertonic saline (150 mL of 1.4%-4.6% saline) twice

daily over 30 minutes for 6-12 days, and dietary sodium intake during treatment and
after discharge 120 mmol/day
furosemide 250 mg IV twice daily without hypertonic saline for 6-12 days, and
dietary sodium intake during treatment and after discharge 80 mmol/day
both groups had fluid intake 1,000 mL/day and were discharged on furosemide 50-125 mg
orally twice daily
mean follow-up 57 months
comparing hypertonic saline plus moderate sodium restriction vs. standard treatment with
severe sodium restriction
readmission for worsening heart failure in 18.5% vs. 34.2% (p < 0.001, NNT 7)
mortality 12.9% vs. 23.8% (p < 0.001, NNT 10)
Reference - Am J Med Sci 2011 Jul;342(1):27
randomized trial with 107 patients
107 patients aged 65-90 years (two-thirds male) with advanced refractory heart failure
were randomized to 1 of 2 groups
furosemide 500-1,000 mg IV plus hypertonic saline (150 mL of 1.4%-4.6% saline)
twice daily over 30 minutes for 6-12 days, and dietary sodium intake during
treatment and after discharge 120 mmol/day with fluid intake 1,000 mL/day
furosemide 500-1,000 mg IV twice daily without hypertonic saline for 6-12 days,
and dietary sodium intake during treatment and after discharge 80 mmol/day with
fluid intake 1,000 mL/day
inclusion criteria were
uncompensated New York Heart Association (NYHA) class IV heart failure of
varying etiology (62 ischemic, 26 hypertensive, 19 dilated) and ejection fraction <
35% despite maximal medical therapy
history of low urinary volume and low salt excretion despite adequate kidney
function and use of ≥ 1 diuretic for ≥ 2 weeks
comparing hypertonic saline plus moderate sodium restriction vs. standard treatment with
greater sodium restriction
readmission for worsening heart failure in 47% vs. 80% (p < 0.001, NNT 3)
mortality 45% vs. 87% (p < 0.001, NNT 3)
Reference - Am Heart J 2003 Mar;145(3):459
reduction in 30-day readmission rate with hypertonic saline reported in randomized trial of same
treatment combinations with 94 patients and same authors, unclear if this is duplication of the
same data (J Am Coll Cardiol 2005 Jun 21;45(12):1997)
DynaMed commentary -- meta-analysis by these authors (focusing on the sodium restriction
component of treatment) was retracted because 2 of the articles contained duplicate data and
original data was no longer available due to computer failure (Heart 2013 Jun;99(11):820)
Medications
Diuretics
Recommendations from professional organizations for diuretics
American College of Cardiology Foundation and American Heart Association (ACCF/AHA)

recommendations(6)
in hospitalized patients
promptly treat patients with significant fluid overload with IV loop diuretics to reduce
morbidity (ACCF/AHA Class I, Level B)
in patients already receiving loop diuretics (ACCF/AHA Class I, Level B)
initial IV dose should equal or exceed chronic oral daily dose, may be given as
intermittent boluses or continuous infusion
serially assess urine output and signs and symptoms of congestion; titrate diuretic
dose to relieve symptoms, reduce excess fluid volume, and avoid hypotension
monitor treatment effect with careful measurement of (ACCF/AHA Class I, Level C)
fluid intake and output, vital signs and body weight determined at same time every day
clinical signs and symptoms of systemic perfusion and congestion
during use of IV diuretics or active medication titration - daily serum electrolytes, blood
urea nitrogen, and creatinine
if diuresis inadequate to relieve congestion, consider intensification of diuresis with either of
higher doses of IV loop diuretics (ACCF/AHA Class IIa, Level B)
addition of second diuretic (such as thiazide) (ACCF/AHA Class IIa, Level B)
consider low-dose dopamine infusion in addition to loop diuretic therapy to improve diuresis and
better preserve renal function and renal blood flow (ACCF/AHA Class IIb, Level B)
European Society of Cardiology (ESC) recommendations(7)

IV loop diuretics recommended for hospitalized patients with signs and symptoms of fluid
overload to improve symptoms (ESC Class I, Level C)
regularly monitor symptoms, urine output, renal function, and electrolytes during use of IV
diuretics (ESC Class I, Level C)
diuretic dosing and administration
in patients with new-onset acute heart failure or chronic decompensated heart failure who
are not taking oral diuretics, IV furosemide (or equivalent) at initial dose 20-40 mg
recommended (ESC Class I, Level B)
in patients taking chronic oral diuretics, initial IV dose should be at least equivalent to oral
dose (ESC Class I, Level B)
give diuretic as either intermittent boluses or continuous infusion and adjust dose and
duration to patients' symptoms and clinical status (ESC Class I, Level B)
consider combination loop diuretic with either thiazide-type diuretic or spironolactone in patients
with resistant edema or insufficient symptomatic response (ESC Class IIb, Level C)
see Diuretics for heart failure for more information
General information and dosing for diuretics
mechanism of action - preload reduction

loop diuretics
no large trial has examined diuretics for acute decompensated heart failure, but loop diuretics are
generally considered first-line therapy with nonloop diuretics used adjunctively(1)
examples include
furosemide
oral dosing
usual initial dose 20-80 mg
may repeat same dose 6-8 hours after initial dose or increase dose by 20-40
mg increments and give no sooner than 6-8 hours after last dose until desired
response obtained
usual maximum dose 600 mg/day
IV dosing
initial bolus IV dose about twice usual daily dose, adjust dose based on urine
output
for acute pulmonary edema, consider 40 mg IV dose, and may give additional
80 mg IV dose 1 hour after initial dose
if diuretic resistance present, consider sequential nephron blockade or
continuous infusion at 5-30 mg per hour
bumetanide
oral dosing
usual initial total daily dose 0.5-2 mg
repeat dose at 4-5 hour intervals until desired response obtained
usual maximum 10 mg/day
IV dosing
usual initial dose 0.5-1 mg
repeat dose every 2-3 hours until desired response obtained
usual maximum dose 10 mg/day
if diuretic resistance present, consider sequential nephron blockade or
continuous infusion
loop diuretics produce significantly greater volume of diuresis then other classes of diuretics,
especially in setting of renal insufficiency, and are diuretics of choice for treatment of acute heart
failure(1)
loop diuretics should generally be used in combination with vasodilator and venodilator therapies
with careful monitoring to avoid overdiuresis(1)
see below for recommendations of loop diuretics in hospitalized patients
sequential nephron blockade with thiazide or thiazide-like diuretics
thiazide or thiazide-like diuretics may be added to loop diuretics for synergistic effect on
diuresis, known as "sequential nephron blockade" (J Am Coll Cardiol 2010 Nov 2;56(19):1527)
examples may include
metolazone (Zaroxolyn)
usual dose 2.5-10 mg once daily plus loop diuretic
for severe heart failure, may consider 2.5-5 mg once or twice daily plus a loop
diuretic
hydrochlorothiazide (HCTZ) 25-100 mg/day in 1-2 doses plus loop diuretic
IV chlorothiazide (Diuril) 500-1,000 mg once daily plus loop diuretic
potassium-sparing diuretics
may be useful in patients with fluid overload and hypokalemia
examples may include
amiloride (Midamor) 5 mg once daily initially, maximum 20 mg/day
triamterene (Dyrenium) 50-75 mg twice daily initially, maximum 200 mg/day
Efficacy of diuretics
IV furosemide within 60 minutes of arrival at emergency department associated with decreased

in-hospital mortality compared to later treatment within 24 hours in patients with acute heart
failure (level 2 [mid-level] evidence)
1,291 patients ≥ 20 years old (mean age 79 years) diagnosed with acute heart failure within 3
hours of first evaluation and treated with furosemide IV within 24 hours of arrival at emergency
department were assessed for all-cause mortality up to 30 days
exclusion criteria included IV medication before arrival at emergency department, heart
transplant, chronic hemo- or peritoneal dialysis, acute myocarditis, need for urgent
coronary revascularization, brain natriuretic peptide < 100 pg/mL, or N-terminal pro-B-
type natriuretic peptide < 300 pg/mL
481 patients had furosemide IV < 60 minutes after arriving at emergency department and
810 patients had furosemide IV ≥ 60 minutes after arrival
47% of < 60 minutes group and 58% of ≥ 60 minutes group presented at > 2 days after
symptom onset
median time to furosemide was 90 minutes
propensity score for likelihood of time point of treatment with furosemide was calculated for
each patient using multiple factors including arrival by ambulance, demographics, blood
pressure, heart rate, signs of congestion at baseline, chronic obstructive pulmonary disease, blood
chemistry profile values, and use of angiotensin-converting enzyme inhibitor or loop diuretic
propensity-matched analysis performed in 708 patients
in-hospital mortality was 2.3% in < 60 minutes group vs. 6% in ≥ 60 minutes group (p = 0.002)
IV furosemide treatment at < 60 minutes associated with
decreased in-hospital mortality
in overall analysis (adjusted odds ratio OR 0.39, 95% CI 0.2-0.76)
in propensity-matched analysis (adjusted OR 0.41, 95% CI 0.18-0.89)
nonsignificant decrease in 30-day mortality
in overall analysis (adjusted OR 0.56, 95% CI 0.13-1)
in propensity-matched analysis (adjusted OR 0.49, 95% CI 0.22-1.05)
Reference - REALITY-AHF (J Am Coll Cardiol 2017 Jun 27;69(25):3042)
continuous infusion and intermittent bolus of furosemide appear to have similar effect on patient
assessment of symptoms (level 2 [mid-level] evidence)
based on randomized trial with allocation concealment not stated
308 patients with acute decompensated heart failure on oral loop diuretic ≥ 1 month randomized
to furosemide in 1 of 4 groups for up to 72 hours
bolus low-dose IV every 12 hours
bolus high-dose IV every 12 hours
low-dose continuous infusion
high-dose continuous infusion
low-dose equivalent to previous oral dose, high-dose was 2.5 times previous oral dose
at 48 hours, treating physician could increase or decrease dose (with blinding maintained) or
switch patient to oral loop diuretic (open label)
no significant differences in patient's global assessment of symptoms or change in creatinine
level among any group

high-dose strategy associated with greater diuresis (greater weight loss, greater relief from
dyspnea) but also transient worsening in renal function
Reference - DOSE trial (N Engl J Med 2011 Mar 3;364(9):797 full-text), editorial can be found
in N Engl J Med 2011 Mar 3;364(9):877
continuous furosemide appears to have similar effect on creatinine levels and urine output as
bolus furosemide in patients hospitalized for heart failure (level 3 [lacking direct] evidence)
based on small randomized trial without clinical outcomes
41 patients hospitalized with heart failure and volume overload randomized to furosemide
delivered by bolus injection vs. continuous infusion
similar mean doses of furosemide over first 48 hours
no significant difference in creatinine change or urine output by hospital stay day 3 or discharge
Reference - Am J Cardiol 2010 Jun 15;105(12):1794
continuous infusion of loop diuretics may be safer and more effective than intermittent boluses
based on Cochrane review with limited evidence
systematic review of 8 randomized trials with 254 patients
urine output was greater with continuous infusion (based on 7 trials, weighted mean difference
271 mL/24 hours)
no differences in hypokalemia and hypomagnesemia but wide confidence intervals make this
finding unreliable
continuous infusion associated with less adverse effects of tinnitus and hearing loss
continuous infusion reduced hospital stay by mean 3.1 days in 1 trial
continuous infusion associated with lower all-cause mortality in 2 trials
Reference - Cochrane Database Syst Rev 2005 Jul 20;(3):CD003178 (review updated 2008 Sep
8)
reviews of diuretic therapy for acute heart failure can be found in

J Cardiovasc Med (Hagerstown) 2010 Aug;11(8):563
Am J Ther 2009 Jan-Feb;16(1):93
Curr Heart Fail Rep 2008 Sep;5(3):153
Low-dose dopamine to augment diuresis
dopamine is an endogenous hormone that has dose-dependent physiologic (renal and cardiac) effects(2)
2-5 mcg/kg/minute causes direct stimulation of beta-adrenergic receptors in the heart and
increase renal blood flow
American College of Cardiology Foundation/American Heart Association (ACCF/AHA) heart failure
guideline(6)
low-dose dopamine infusion may be considered in addition to loop diuretic therapy to improve
diuresis and better preserve renal function and renal blood flow (ACCF/AHA Class IIb, Level B)
Efficacy of low-dose dopamine to augment diuresis in patients with acute heart failure
low-dose dopamine associated with reduced risk for worsening markers of renal function in
patients with heart failure (level 3 [lacking direct] evidence)
based on nonclinical outcomes in systematic review of trials with methodologic limitations
systematic review of 7 studies (6 randomized controlled trials and 1 retrospective cohort)

evaluating use of low-dose dopamine (≤ 5 mcg/kg/minute) in 587 patients with heart
failure
6 studies compared addition of dopamine to a loop diuretic vs. loop diuretic alone
1 randomized trial compared dopamine plus human atrial natriuretic peptide (hANP)
vs. furosemide plus hANP
all but 1 trial had unclear allocation concealment; high-quality trial (ROSE trial) did not
have clinical outcomes
comparing dopamine use to no dopamine use, dopamine associated with
increased
estimated glomerular filtration rate (pooled mean difference 7.44 mL/min/1.73
m2, 95% CI 1.92-12.95 mL/min/1.73 m2) in analysis of 3 trials and 1 cohort
study with 306 patients
urine output (standardized mean difference 0.58, 95% CI 0.15-1.01) in
analysis of 6 trials and 1 cohort study with 580 patients, results limited by
significant heterogeneity
decreased
creatinine (pooled mean difference -0.36 mg/dL, 95% CI -0.64 to -0.08
mg/dL) in analysis of 4 trials and 1 cohort study with 326 patients, results
limited by significant heterogeneity
blood urea nitrogen (pooled mean difference -6.97 mg/dL, 95% CI -13.12 to
-0.81 mg/dL) in analysis of 3 trials and 1 cohort study with 302 patients,
results limited by significant heterogeneity
no significant differences in mortality or readmission rates
Reference - Int J Cardiol 2016 Aug 5;222:1003
low-dose dopamine plus low-dose furosemide may be as effective as high-dose furosemide
for diuresis and dyspnea reduction (level 2 [mid-level] evidence) and may reduce risk of
worsening renal function (level 3 [lacking direct] evidence) in patients with acute
based on small randomized trial
60 patients (mean age 76 years) with acute decompensated heart failure had furosemide 40
mg IV bolus and were randomized to 1 of 2 groups
low-dose dopamine plus low-dose furosemide (furosemide 5 mg/hour plus
dopamine 5 mcg/kg/minute continuous infusion for 8 hours)
high-dose furosemide (20 mg/hour continuous infusion for 8 hours)
no significant difference between groups in improvement in mean dyspnea score during
treatment
comparing low-dose furosemide plus low-dose dopamine vs. high-dose furosemide
mean hourly excreted urine volume during treatment 278 mL vs. 272 mL (not
significant)
worsening renal function (defined as increase in serum creatinine of > 0.3 mg/dL at
24 hours) in 6.7% vs. 30% (p = 0.042, NNT 5)
mean decrease in potassium at 24 hours 0.2 mEq/L (0.2 mmol/L) vs. 0.4 mEq/L (0.4
mmol/L) (p = 0.027)
length of stay 6.1 days vs. 5.3 days (not significant)
60-day all-cause mortality 10% vs. 10% (not significant)
60-day cardiovascular-related mortality 6.7% vs. 10% (not significant)
60-day all-cause rehospitalization 20% vs. 6.7% (not significant)

Reference - DAD-HF trial (J Card Fail 2010 Dec;16(12):922)
addition of low-dose dopamine or low-dose nesiritide to diuretic does not improve markers
of decongestion or renal function in patients with acute heart failure and renal dysfunction
(level 3 [lacking direct] evidence)
based on nonclinical outcomes from randomized trial
360 patients (median age 70 years, 73% men) hospitalized with acute heart failure and
renal dysfunction (estimated glomerular filtration rate 15-60 mL/minute/1.73 m2)
randomized within 24 hours of admission to diuretic therapy plus 1 of 3 interventions for
72 hours and followed up to 180 days
dopamine 2 mcg/kg/minute
nesiritide 0.005 mcg/kg/minute without bolus
placebo
diuretic therapy consisted of IV loop furosemide at 2.5 times total daily oral outpatient
dose (maximum 600 mg/day) or 80 mg/day if naive to prior diuretic treatment
median ejection fraction at baseline 33%
94% had data available for urinary volume (measure of decongestion) and 86% had data
available for serum cystatin C (marker of renal function) at 72 hours, but all patients
included in intention-to-treat analysis
comparing dopamine vs. nesiritide vs. placebo
72-hour cumulative urine volume 8,524 mL vs. 8,574 mL vs. 8,296 mL (no
significant differences in pairwise comparisons)
72-hour change in serum cystatin C 0.12 mg/L vs. 0.11 mg/L vs. 0.07 mg/L (no
significant differences in pairwise comparisons)
no significant differences among groups in mortality at 60 or 180 days or serious adverse
events at 60 days
Reference - ROSE trial (JAMA 2013 Dec 18;310(23):2533)
addition of low-dose dopamine to diuretic may increase urinary output in patients
with reduced ejection fraction (level 3 [lacking direct] evidence), but may decrease
urinary output and increase treatment failure in patients with preserved ejection
fraction (level 2 [mid-level] evidence)
based on post hoc subgroup analysis of ROSE trial
358 patients with baseline ejection fraction (EF) assessment were included
reduced EF (≤ 40%) in 62% (mean age 69 years, 80% men, mean body mass
index 30.1 kg/m2)
preserved EF in 38% (mean age 74 years, 63% men, mean body mass index
33 kg/m2)
treatment failure defined as development of cardiorenal syndrome type 1, worsening
or persistent heart failure requiring additional vasoactive agents, ultrafiltration, or
mechanical ventilation, or significant hypotension or tachycardia.
comparing dopamine vs. placebo
in patients with reduced EF
72-hour cumulative urine volume 8,703 mL vs. 7,650 mL (p = 0.029)
treatment failure in 29.6% vs. 37.3% (not significant)
death or rehospitalization for heart failure at 60 days in 22.9% vs.
27.8% (not significant)
weight change -8.9 lbs vs. -5.1 lbs (p = 0.016)

in patients with preserved EF
72-hour cumulative urine volume 7,300 mL vs. 8,750 mL (p = 0.01)
treatment failure in 29.5% vs. 10% (p = 0.033, NNH 5)
death or rehospitalization for heart failure at 60 days in 37.3% vs.16.9%
(p = 0.038, NNH 4)
weight change -6 lbs vs. +4.6 lbs (p = 0.006)
nesiritide associated with less weight loss than placebo in patients with preserved EF
(difference 3.2 lbs, p = 0.024) but not reduced EF, and no significant differences in
either EF subgroup in 72-hour cumulative urine volume or mortality or
rehospitalization for heart failure at 60 days
Reference - ROSE trial (Circ Heart Fail 2016 Aug;9(8))
see Dopamine for additional drug information
Vasodilators
Recommendations from professional organizations
European Society of Cardiology (ESC) recommendations for vasodilators(7)

IV vasodilators suggested for symptom relief in patients with acute heart failure and systolic
blood pressure > 90 mm Hg who do not have symptomatic hypotension (ESC Class IIa, Level B)
frequently monitor symptoms and blood pressure during use of IV vasodilators (ESC Class IIa,
Level B)
IV vasodilators suggested as initial therapy in patients with hypertensive acute heart failure to
improve symptoms and reduce congestion (ESC Class IIa, Level B)
dosing recommendations
IV nitroglycerin - start with 10-20 mcg/minute and increase up to 200 mcg/minute
IV isosorbide dinitrate - start with 1 mg/hour and increase up to 10 mg/hour (IV
formulation not available in United States as of August 11, 2017)
IV nitroprusside - start with 0.3 mcg/kg/minute and increase up to 5 mcg/kg/minute
IV nesiritide - bolus 2 mcg/kg plus infusion 0.01 mcg/kg/minute
Nitrates
Recommendations for nitrates
IV nitroglycerin or nitroprusside may be considered as adjunct to diuretic therapy for relief of dyspnea
in patients admitted with acutely decompensated heart failure in absence of symptomatic hypotension
(ACCF/AHA Class IIb, Level A)(6)
DynaMed commentary -- evidence cited in ACCF/AHA and ESC guidelines does not appear to clearly
support symptomatic or clinical benefit with nitrates
nitrates for acute heart failure syndrome have insufficient evidence for effects on clinical
outcomes
based on Cochrane review
systematic review of 4 randomized trials evaluating nitrates (isosorbide dinitrate, nitroglycerin)
in 634 adults with acute heart failure syndrome
no trials comparing nitrates to placebo reported outcomes for efficacy

comparing isosorbide dinitrate to furosemide in analyses of 2 trials with 52 adults
isosorbide dinitrate associated with decreased blood pressure
no significant differences in heart rate, cardiac index, and pulmonary artery occlusion
pressure
comparing nitroglycerine plus N-acetylcysteine vs. furosemide plus morphine, no significant
difference in dyspnea in 1 trial with 87 adults
comparing nitroglycerin vs. nesiritide, no significant difference in ischemic events in 1 trial with
347 adults
Reference - Cochrane Database Syst Rev 2013 Aug 6;(8):CD005151
Nitroglycerin
use of IV nitroglycerin in acute decompensated heart failure

nitric oxide-mediated vasodilatory effect can lead to beneficial hemodynamic effects
may reduce myocardial ischemia and mitral regurgitation
evidence limited to mostly hemodynamic evaluations, doses > 120 mcg/minute may be needed in
heart failure to achieve vasodilatory response
no significant improvement in symptoms in 1 randomized placebo-controlled trial
Reference - J Cardiovasc Pharmacol Ther 2004 Dec;9(4):227
nitroglycerin and nesiritide associated with reduced dyspnea and pulmonary capillary
wedge pressure compared to placebo but nesiritide improves hemodynamic function more
effectively than IV nitroglycerin (level 2 [mid-level] evidence)
based on randomized trial with inadequate power to establish similar efficacy for clinical
outcomes
489 inpatients with dyspnea at rest from decompensated heart failure randomized to
nesiritide vs. nitroglycerin vs. placebo IV for 3 hours, then nesiritide vs. nitroglycerin for
24 hours
nesiritide associated with greater reductions in pulmonary capillary wedge pressure
(PCWP) than nitroglycerin at 3 hours and at 24 hours
nitroglycerin associated with greater reductions in PCWP than placebo
both active drugs improved dyspnea compared to placebo, no differences between drugs in
dyspnea at 3 hours or at 24 hours
nesiritide less likely than nitroglycerin to cause headache (8% vs. 20%)
Reference - VMAC trial (JAMA 2002 Mar 27;287(12):1531), correction can be found in
JAMA 2002 Aug 7;288(5):577, editorial can be found in JAMA 2002 Mar
27;287(12):1578, commentary can be found in JAMA 2002 Aug 7;288(5):571
tachyphylaxis may develop, requiring incremental increases in dosing (Heart Fail Rev 2007
Jun;12(2):143)
Nitroprusside
nitroprusside is a short-acting arterial vasodilator(1)

IV nitroglycerin or nitroprusside may be considered as adjunct to diuretic therapy for relief of dyspnea
in patients admitted with acutely decompensated heart failure in absence of symptomatic hypotension
nitroprusside might reduce mortality if started late (but increase mortality if started early) in
patients with elevated left ventricular filling pressure following acute myocardial infarction (level
2 [mid-level] evidence)
based on subgroup analysis of randomized trial
812 men with presumed acute myocardial infarction and left ventricular filling pressure ≥ 12 mm
Hg were randomized to sodium nitroprusside vs. placebo via 48-hour infusion
comparing sodium nitroprusside vs. placebo
mortality at 21 days 11.5% vs. 10.4% (not significant)
mortality at 13 weeks 17% vs. 19% (not significant)
in subgroup of patients with treatment starting within 9 hours of onset of pain, mortality at
13 weeks 24.2% vs. 12.7% (p = 0.025, NNH 8)
in subgroup of patients with treatment starting after 9 hours of onset of pain, mortality at
13 weeks 14.4% vs. 22.3% (p = 0.04, NNT 13)
Reference - N Engl J Med 1982 May 13;306(19):1129
sodium nitroprusside may be associated with reduced mortality in patients with acute
decompensated heart failure (level 2 [mid-level] evidence)
175 patients admitted with acute decompensated heart failure with cardiac index ≤ 2.1
L/minute/m2 evaluated
78 patients (45%) were treated with sodium nitroprusside
comparing patients treated with sodium nitroprusside vs. controls
all-cause mortality 29% vs. 44% (p = 0.005, NNT 7)
rehospitalization rate 58% vs. 56% (not significant)
Reference - J Am Coll Cardiol 2008 Jul 15;52(3):200
nitroprusside therapy in patients with systolic heart failure and severe aortic stenosis reported to
significantly improve hemodynamic parameters (level 3 [lacking direct] evidence)
based on case series without clinical outcomes
25 patients with severe aortic stenosis (aortic valve area ≤ 1 cm2) and reduced ejection fraction
(≤ 35%) and cardiac index (≤ 2.2 L/minute/m2 Fick method) without systemic hypotension but
admitted to an intensive care unit for invasive hemodynamic monitoring received IV
nitroprusside therapy titrated to produce mean arterial pressure 60-70 mm Hg
after 24 hours
cardiac index improved from 1.6 to 2.52 L/minute/m2 (p < 0.001)
mean arterial pressure decreased from 81 to 69 mm Hg (p < 0.001)
pulmonary capillary wedge pressure decreased from 27 to 23 mm Hg (p = 0.004)
systemic vascular resistance decreased from 1,926 to 1,042 dyn·sec/cm5 (p < 0.001)
stroke volume increased from 32 to 54 mL (p < 0.001)
Reference - N Engl J Med 2003 May 1;348(18):1756, editorial can be found in N Engl J Med
2003 May 1;348(18):1735, commentary can be found in N Engl J Med 2003 Aug 21;340(8):811
review of nitroprusside in decompensated heart failure can be found in Curr Heart Fail Rep 2009
Sep;6(3):182
Reviews of nitrates in heart failure
review of nitrates in heart failure can be found in Cardiovasc Drugs Ther 1994 Jun;8(3):501
review of nitrate therapy in heart failure can be found in Cardiology 1991;79 Suppl 2:5
reviews of vasodilator therapy in the treatment of acute heart failure can be found in
Heart Fail Rev 2009 Dec;14(4):299 full-text
Crit Care Med 2008 Jan;36(1 Suppl):S95
Nesiritide
IV nesiritide may be considered as adjuvant to diuretic therapy for relief of dyspnea in patients
admitted with acutely decompensated heart failure in absence of symptomatic hypotension
prescribing information
brand name Natrecor
vasodilator, biosynthetic form of human B-type natriuretic peptide
FDA approved for acutely decompensated heart failure with dyspnea at rest or with minimal
activity (New York Heart Association Class IV symptoms)
manufacturer recommends restricting use to patients with acutely decompensated heart failure
and dyspnea at rest
some clinicians suggest role of nesiritide limited to patients who do not respond to nitroglycerin
and cannot be treated with nitroprusside
dosing
initial bolus 2 mcg/kg IV over 1 minute
initial infusion rate 0.01 mcg/kg/minute
titration in increments of 0.005 mg/kg/minute, at least 3 hours between dose increases
maximum dose 0.03 mcg/kg/minute
Pregnancy Category C
adverse effects may include hypotension, renal dysfunction, ventricular tachycardia, bradycardia
see also Nesiritide
efficacy for nesiritide in acute heart failure, has conflicting evidence for dyspnea as it might improve
dyspnea compared to placebo in 1 trial, appears similar to nitroglycerin for improving dyspnea in 1
trial, and appears to have no effect on dyspnea in 1 randomized trial
nesiritide may not increase or decrease mortality, rehospitalization, or dyspnea in patients
with acute decompensated heart failure (level 2 [mid-level] evidence) and increases risk for
hypotension
based on randomized trial with inadequate statistical power
7,141 patients with acute decompensated heart failure randomized to nesiritide vs. placebo
for 24-168 hours in addition to standard care
power calculation based on expected event rate of 11.4% with nesiritide and 14% with
placebo for composite of rehospitalization for heart failure or death due to any cause
though day 30
dyspnea end point was considered significant if p values were ≤ 0.005 at both 6 and 24
hours or if either of two p values was ≤ 0.0025
comparing nesiritide vs. placebo
rehospitalization for heart failure or death from any cause within 30 days in 9.4% vs.
death from any cause at 30 days in 3.6% vs. 4% (not significant)
markedly or moderately improved dyspnea at 6 hours in 44.5% vs. 42.1% (not
significant)
markedly or moderately improved dyspnea at 24 hours in 68.2% vs. 66.1% (not
significant)
worsening renal function (defined by > 25% decrease in estimated glomerular
filtration rate) in 31.4% vs. 29.5% (not significant)
hypotension in 26.6% vs. 15.3% (p < 0.001, NNH 8)
Reference - ASCEND-HF trial (N Engl J Med 2011 Jul 7;365(1):32 full-text), editorial can
be found in N Engl J Med 2011 Jul 7;365(1):81 (correction can be found in N Engl J Med
2011 Aug 25;365(8):773)
nesiritide improves hemodynamic function more effectively than IV nitroglycerin or
placebo (level 3 [lacking direct] evidence), but not clearly more effective than nitroglycerin
for symptom improvement (level 2 [mid-level] evidence)
based on randomized trial with inadequate power to establish similar efficacy for clinical
outcomes
489 inpatients with dyspnea at rest from decompensated heart failure randomized to
nesiritide vs. nitroglycerin vs. placebo IV for 3 hours, then nesiritide vs. nitroglycerin for
24 hours
nesiritide associated with greater reductions in pulmonary capillary wedge pressure
(PCWP) than nitroglycerin at 3 hours and at 24 hours
nitroglycerin associated with greater reductions in PCWP than placebo
both active drugs improved dyspnea compared to placebo, no differences between drugs in
dyspnea at 3 hours or at 24 hours
nesiritide less likely than nitroglycerin to cause headache (8% vs. 20%)
Reference - VMAC trial (JAMA 2002 Mar 27;287(12):1531), correction can be found in
JAMA 2002 Aug 7;288(5):577, editorial can be found in JAMA 2002 Mar
27;287(12):1578, commentary can be found in JAMA 2002 Aug 7;288(5):571
nesiritide may improve hemodynamic function and symptoms in patients with
decompensated heart failure (level 2 [mid-level] evidence)
based on small randomized placebo-controlled trial and larger open-label randomized trial
127 patients with Swan-Ganz catheter randomized to nesiritide (0.015 or 0.03
mcg/kg/minute) vs. placebo IV for 6 hours
comparing placebo vs. nesiritide 0.015 mcg/kg/minute vs. nesiritide 0.03 mcg/kg/minute
improvements in global clinical status in 14% vs. 60% (NNT 3) vs. 67% (NNT 2)
reduced dyspnea in 12% vs. 57% (NNT 3) vs. 53% (NNT 3)
reduced fatigue in 5% vs. 32% (NNT 4) vs. 38% (NNT 3)
305 patients without hemodynamic monitoring randomized to open-label nesiritide vs.
standard agents for up to 7 days
comparison trial found similar improvements in global clinical status, dyspnea and fatigue
Reference - N Engl J Med 2000 Jul 27;343(4):246, correction can be found in N Engl J
Med 2000 Nov 16;343(20):1504, commentary can be found in N Engl J Med 2005 Jul
14;353(2):113
study funded by drug manufacturer (correction in N Engl J Med 2000 Sep 21;343(12):896)
Inotropic agents
Recommendations from professional organizations for inotropic agents
American College of Cardiology Foundation/American Heart Association (ACCF/AHA) heart failure
guideline(6)
low-dose dopamine infusion may be considered in addition to loop diuretic therapy to improve
diuresis and better preserve renal function and renal blood flow (ACCF/AHA Class IIb, Level B)
temporary IV inotropic support (such as dopamine, dobutamine, or milrinone) recommended in
patients with cardiogenic shock (ACCF/AHA Class I, Level C)
to maintain systemic perfusion and preserve end-organ performance
until definitive therapy (such as coronary revascularization, mechanical circulatory
support, or heart transplantation) or resolution of the acute precipitating problem
short-term, continuous IV inotropic support may be reasonable in hospitalized patients with
documented severe systolic dysfunction, low blood pressure, and significantly depressed cardiac
output to maintain systemic perfusion and preserve end-organ performance (ACCF/AHA Class
IIb, Level B)
continuous IV inotropic support reasonable as "bridge therapy" while awaiting mechanical
circulatory support or cardiac transplantation in patients with stage D heart failure refractory to
guideline-directed medical therapy and device therapy (ACCF/AHA Class IIa, Level B)
long-term, continuous IV inotropic support may be considered as palliative therapy for symptom
control in select patients with stage D heart failure despite optimal guideline-directed medical
therapy and device therapy who are not eligible for either mechanical circulatory support or
cardiac transplantation (ACCF/AHA Class IIb, Level B)
use of IV inotropic agents is potentially harmful in hospitalized patients without documented
severe systolic dysfunction, low blood pressure, or impaired perfusion, and evidence of
significantly depressed cardiac output, with or without congestion (ACCF/AHA Class III Harm,
Level B)
short-term IV inotropic agents may be considered in patients with hypotension (systolic blood
pressure < 90 mm Hg) and/or symptoms/signs of hypoperfusion despite adequate filling status to
increase cardiac output, increase blood pressure, improve peripheral perfusion, and maintain end-
organ function (ESC Class IIb Level C)
IV levosimendan or phosophodiesterase III (PDE III) inhibitor may be considered to reverse
effect of beta blockade if beta blockade thought to be contributing to hypotension with
subsequent hypoperfusion (ESC Class IIb Level C)
inotropic agents not recommended due to safety concerns unless patient is symptomatically
hypotensive or hypoperfused (ESC Class III Level A)
monitor electrocardiogram and blood pressure when using inotropic agents and vasopressors due
to potential drug-induced arrhythmias, myocardial ischemia, and (in case of levosimendan and
PDE III inhibitors) hypotension (ESC Class I, Level C)
Dopamine
dopamine is an endogenous hormone that has dose-dependent physiologic (renal and cardiac) effects(2)
2-5 mcg/kg/minute causes direct stimulation of beta-adrenergic receptors in the heart
5-15 mcg/kg/minute stimulates alpha and beta adrenergic receptors leading to increased heart
rate and peripheral vasoconstriction
major side effect is tachycardia (more pronounced than with dobutamine)(2)
see Dopamine for additional drug information
Dobutamine
dobutamine is a synthetic catecholamine which acts mainly as beta1-receptor agonist(1)

rate of infusion used to increase cardiac output ranges from 2.5 to 15 mcg/kg/minute(2)
administration usually results in modest decrease in systemic vascular resistance and venous filling
pressures, but overall effect on blood pressure is variable(2)
see Dobutamine for additional drug information
Milrinone
milrinone inhibits phosphodiesterase III increasing cyclic adenosine monophosphate levels and cardiac
contractility and vasodilation(1)
milrinone has no apparent clinical benefit in patients with decompensated systolic heart failure
but increased hypotension and arrhythmias (level 2 [mid-level] evidence)
based on randomized trial with allocation concealment not stated
951 patients (at 78 different centers in United States) hospitalized for exacerbation of chronic
systolic heart failure but without systemic hypotension were randomized to milrinone 0.5
mcg/kg/minute vs. saline placebo by IV infusion for 48-72 hours
comparing milrinone vs. placebo
median days hospitalized for cardiovascular-related problems 6 vs. 7 (not significant)
in-hospital mortality 3.8% vs. 2.3% (not significant)
60-day mortality 10.3% vs. 8.9% (not significant)
combined outcome of death or readmission in 35% vs. 35.3% (not significant)
sustained hypotension required intervention in 10.7% vs. 3.2% (p < 0.001, NNH 13)
new atrial arrhythmias in 4.6% vs. 1.5% (p = 0.004, NNH 32)
Reference - OPTIME-CHF trial (JAMA 2002 Mar 27;287(12):1541 full-text), editorial can be
found in JAMA 2002 Mar 27;287(12):1578, full description of methods can be found in Am
Heart J 2000 Jan;139(1 Pt 1):15
milrinone dosing 0.125-0.75 mcg/kg/minute (bolus dose not recommended)(6)
role of milrinone limited
used for temporary symptomatic improvement or as bridge to cardiac transplantation
complications include tachyarrhythmia, hypotension, thrombocytopenia
Reference - Treat Guidel Med Lett 2002 Dec;1(4):19 TOC
other phosphodiesterase inhibitors include inamrinone and vesnarinone(1)
Digoxin
role of digoxin therapy for acute decompensated heart failure is poorly defined(1)
long-term therapy should not be discontinued during acute episodes of heart failure(1)
digoxin associated with decrease in 30-day all-cause hospital readmission in patients with acute
heart failure and ejection fraction < 45% (level 2 [mid-level] evidence)
921 patients (mean age 76 years and 56% women) with acute heart failure who received digoxin
were matched to 921 controls without digoxin
30-day all-cause hospital readmission in 17% with digoxin

compared to no digoxin, digoxin associated with decreased risk of
30-day all-cause hospital readmission in patients with ejection fraction < 45% (hazard ratio
[HR] 0.63, 95% CI 0.47-0.83)
12-month heart failure readmission in patients with ejection fraction < 45% (HR 0.63, 95%
CI 0.5-0.79)
12-month all-cause mortality overall (HR 0.83, 95% CI 0.7-0.98)
no significant association between digoxin use and
30-day all-cause hospital readmission in patients with ejection fraction ≥ 45%
30-day hospital readmission due to heart failure overall
Reference - Am J Med 2014 Jan;127(1):61
see also Digoxin
Levosimendan
levosimendan not available in the United States as of August 11, 2017)

binds to cardiac troponin C in calcium-dependent manner (sensitizes myofilaments to calcium)
producing positive inotropic effect in heart muscle independent of beta-adrenergic stimulation (JAMA
2007 May 2;297(17):1883 full-text)
IV levosimendan may be considered to reverse effect of beta-blockade if beta-blockage thought to be
contributing to hypotension with subsequent hypoperfusion (ESC Class IIb, Level C) (7)
levosimendan may or may not reduce mortality compared to dobutamine in patients with acute
decompensated heart failure, evidence inconsistent
based on 2 randomized trials with inconsistent results
levosimendan and dobutamine may have similar mortality in patients with decompensated
heart failure
1,327 patients with ejection fraction ≤ 30% hospitalized with acute decompensated heart
failure requiring inotropic support (inadequate alleviation of symptoms with standard
diuretic/vasodilator therapy) randomized to levosimendan vs. dobutamine
levosimendan 12 mcg/kg loading dose IV over 10 minutes, then 0.1 mcg/kg infusion
for 50 minutes, then 0.2 mcg/kg for ≤ 23 hours (for total maximum 24 hours therapy
as tolerated)
dobutamine 5 mcg/kg/minute, could be titrated up to 40 mcg/kg/minute, continued ≥
24 hours and tapered according to clinical status
placebo infusions used to maintain blinding
during 180 days of follow-up after study drug infusion
48 patients in levosimendan and 54 in dobutamine group received additional blinded
readministration of study drug
75 patients in levosimendan and 79 in dobutamine group received open-label
administration of additional inotropic medication (almost all patients received
dobutamine in both groups)
comparing levosimendan vs. dobutamine
all-cause mortality at 180 days 26% vs. 28% (95% CI for absolute difference -7.3%
to +3.6%)
all-cause mortality at 30 days 12% vs. 14% (not significant)
no significant differences in rates of improvement in dyspnea and overall global
assessment after 24 hours, or cardiovascular mortality at 180 days

treatment-emergency cardiac failure in 12.3% vs. 17% (p = 0.02, NNT 21)
atrial fibrillation in 9.1% vs. 6.1% (p = 0.05, NNH 33)
hypokalemia in 9.4% vs. 5.9% (p = 0.02, NNH 28)
headache in 8.3% vs. 4.7% (p = 0.01, NNH 27)
ventricular extrasystoles in 6.1% vs. 3.6% (p = 0.05, NNH 40)
Reference - SURVIVE trial (JAMA 2007 May 2;297(17):1883 full-text)
levosimendan may reduce mortality compared to dobutamine in patients with
203 patients with low output heart failure (ejection fraction < 35%, cardiac index < 2.5
L/minute/m2, and mean pulmonary capillary wedge pressure [PCWP] > 15 mm Hg)
judged to require inotropic support were randomized to levosimendan vs. dobutamine for
24 hours
levosimendan 24 mcg/kg over 10 minutes then 0.1 mcg/kg/minute
dobutamine 5 mcg/kg/minute with dose doubled at 2 hours if 30% increase in
cardiac index not achieved
4 patients who did not receive assigned drug appropriately included in intention-to-treat
analysis and classified as nonresponders
comparing levosimendan vs. dobutamine
mortality 8% vs. 17% (p = 0.049, NNT 11)
median days alive and out of hospital in first 180 days was 157 vs. 133 days (p =
0.027)
improvement in hemodynamic parameters (≥ 30% increase in cardiac output and ≤
25% decrease in PCWP) during first 24 hours in 28% vs. 15% (NNT 8)
improved dyspnea in 68% vs. 59% (not significant)
improved fatigue in 63% vs. 47% (not significant)
serious adverse events in 6 vs. 10 patients (no p value reported)
Reference - LIDO trial (Lancet 2002 Jul 20;360(9328):196)
Reviews of inotropic agents
reviews of inotropic therapy for acute heart failure can be found in Heart Fail Rev 2007 Jun;12(2):149,
Expert Opin Pharmacother 2006 Nov;7(16):2179
Beta blockers
initiation of beta blockers recommended after optimization of volume status and successful
discontinuation of IV diuretics, vasodilators, and inotropic agents (ACCF/AHA Class I, Level B)(6)
start at low dose and only in stable patients
extra caution should be used in patients who require inotropes during hospital course
see Beta blockers for heart failure for details
continuation of usual outpatient beta blocker regimen during hospitalization for decompensated
heart failure does not appear to worsen symptoms or increase mortality or length of hospital stay
based on randomized trial without intention-to-treat analysis and without blinding
169 adults (mean age 72 years) with left ventricular ejection fraction < 40% randomized to usual
beta blocker therapy vs. discontinuation upon hospital admission for decompensated heart failure
all patients had been receiving beta blocker therapy (bisoprolol, carvedilol, or atenolol) at stable
dose for ≥ 1 month prior to admission
147 (86.9%) analyzed
no significant differences between groups in
severity of dyspnea or general well-being at days 3 and 8
length of hospital stay
incidence of hospital readmission after 3 months
mortality at 3 months
Reference - B-CONVINCED trial (Eur Heart J 2009 Sep;30(18):2186 full-text), editorial can be
found in Eur Heart J 2009 Sep;30(18):2177 full-text
beta blocker initiation during hospitalization for decompensated heart failure associated with
lower postdischarge mortality, while beta blocker discontinuation associated with higher
postdischarge mortality (level 2 [mid-level] evidence)
among 5,791 patients from OPTIMIZE-HF registry admitted with heart failure to 91 hospitals in
United States (2003-2004), 5,117 had left ventricular function assessed and 2,720 had
documented left ventricular systolic dysfunction
2,373 patients with documented left ventricular systolic dysfunction and without documented
contraindications or intolerance to beta blockers were analyzed
1,350 (57%) had beta blockers before and during admission
632 (27%) newly started beta blockers
79 (3%) had beta blockers withdrawn
303 (13%) were not treated with beta blockers before or during admission
among patients with beta blocker use before admission, withdrawal of beta blockers associated
with
higher mortality at 60-90 days (24.4% vs. 8.7%, adjusted hazard ratio [HR] 2.34, 95% CI
1.2-4.55)
no significant difference in combined outcome of mortality or rehospitalization at 60-90
days (37.7% vs. 36.1%)
among patients not taking beta blocker on admission, new prescription of beta blocker associated
with
lower mortality at 60-90 days (4.5% vs. 13.8%, adjusted HR 0.41, 95% CI 0.22-0.78)
lower rate of mortality or rehospitalization at 60-90 days (27.5% vs. 43.2%, adjusted HR
0.61, 95% CI 0.44-0.83)
Reference - J Am Coll Cardiol 2008 Jul 15;52(3):190
Calcium channel blockers
guideline recommendations
European Society of Cardiology (ESC) recommends avoiding most calcium channel blockers
(except amlodipine or felodipine) due to potential to cause harm, including increase in
sympathetic tone(7)
American College of Cardiology and American Heart Association (ACCF/AHA) guidelines
calcium channel blockers are not recommended as routine treatment for patients with heart
failure with reduced ejection fraction (ACCF/AHA Class III, Level A)
avoid or withdraw most calcium channel blockers (except amlodipine) when possible in
patients with current or prior symptoms of heart failure with reduced ejection fraction as
they may adversely affect the patient's clinical status (ACCF/AHA Class III Harm, Level
B)
nondihydropyridine calcium channel blockers with negative inotropic effects may be
harmful in asymptomatic patients (stage B) with low left ventricular ejection fraction and
no symptoms of heart failure after myocardial infarction (ACCF/AHA Class III Harm,
Level C)
evidence supporting potential harm with using nondihydropyridine calcium channel blockers
diltiazem associated with increased risk for cardiac events in patients with post myocardial
infarction heart failure and pulmonary congestion (level 2 [mid-level] evidence)
based on randomized trial with unclear allocation concealment
2,466 patients (mean age 58 years) hospitalized with acute myocardial infarction in United
States and Canada were randomized to diltiazem 60 mg 4 times daily vs. placebo and
followed for mean 25 months
comparing diltiazem vs. placebo
all-cause death in 13.5% vs. 13.5%
death from cardiac cause in 10% vs. 10.3% (no p value reported)
cardiac events defined as cardiac mortality or recurrent nonfatal infarction
among 1,909 patients without pulmonary congestion on chest x-ray, diltiazem associated
with reduction in number of cardiac events (hazard ratio [HR] 0.77, 95% CI 0.61-0.98)
among 490 patients with pulmonary congestion on chest x-ray, diltiazem associated with
increased number of cardiac events (HR 1.41, 95% CI 1.01-1.96)
Reference - MDPIT trial N Engl J Med 1988 Aug 18;319(7):385
diltiazem associated with late or worsened heart failure in patients with left
ventricular ejection fraction < 40% (level 2 [mid-level] evidence)
based on post hoc secondary analysis of MDPIT trial above
among 623 patients with baseline ejection fraction < 40%, late new or worsened
heart failure in 21% of diltiazem group vs. 12% of placebo group (p = 0.004)
diltiazem-associated increase in frequency of late heart failure increased with greater
decrements in baseline ejection fraction
Reference - Circulation 1991 Jan;83(1):52
Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs)
for patients hospitalized for heart failure who are on chronic therapy, continuation of guideline-directed
medical therapy (including ACE inhibitor or ARB) recommended in absence of hemodynamic
instability or contraindications (ACCF/AHA Class I, Level B)(6)
captopril may produce greater hemodynamic improvements than nitroglycerin in severe heart
failure (level 3 [lacking direct] evidence)
based on randomized crossover trial without clinical outcomes
24 patients with severe heart failure randomized to captopril 25 mg vs. nitroglycerin 0.8 mg
sublingually in crossover trial
comparing captopril vs. nitroglycerin
increase in cardiac index +49% vs. +25% (p < 0.001)
increase in stroke volume index +53.5% vs. +26% (p < 0.001)
increase in stroke work index +55% vs. +28% (p < 0.001)
time to onset of change in hemodynamic parameters 12-19 minutes vs. 16-22 minutes (not
significant)
Reference - Int J Cardiol 1990 Jun;27(3):351
see Angiotensin receptor blockers for heart failure for further information
Aldosterone antagonists (potassium-sparing diuretics)
American College of Cardiology and American Heart Association (ACCF/AHA) guidelines

recommend aldosterone antagonists in selected patients(6)
clinical role is for patients with Stage C heart failure (structural heart disease plus symptoms)
and reduced left ventricular ejection fraction
recommendations are not specifically for use in acute heart failure
addition of aldosterone antagonist recommended in selected patients with New York Heart
Association (NYHA) class II-IV heart failure and left ventricular ejection fraction ≤ 35%, unless
contraindicated, to reduce morbidity and mortality (ACCF/AHA Class I, Level A)
selection criteria include
patients with NYHA class II heart failure should have history of cardiovascular
hospitalization or elevated plasma natriuretic peptide levels
maintain creatinine ≤ 2.5 mg/dL (221 mcmol/L) in men and ≤ 2 mg/dL (176.8
mcmol/L) in women, or (in elderly or patients with low muscle mass) estimated
glomerular filtration rate > 30 mL/minute/1.73 m2
maintain potassium < 5 mEq/L
monitor potassium, renal function, and diuretic dosing at initiation and follow closely to
minimize risk of hyperkalemia and renal insufficiency (typically at 2-3 days and 1 week,
then at least monthly for first 3 months, and every 3 months thereafter); cycle of
monitoring should repeat with any addition of or increase in dose of either angiotensin-
converting enzyme (ACE) inhibitor or angiotensin receptor blocker
risk for hyperkalemia increased with
serum creatinine > 1.6 mg/dL (141.4 mcmol/L), with progressive increased risk with
higher serum creatinine
concomitant use of higher doses of ACE inhibitors (captopril ≥ 75 mg/day, enalapril
or lisinopril ≥ 10 mg/day)
nonsteroidal anti-inflammatory drugs (NSAIDs)
potassium supplements
aldosterone antagonists not ordinarily started in patients with baseline serum potassium >
5 mEq/L
initial dose of spironolactone 12.5 mg or eplerenone 25 mg once daily recommended, dose
may then increase to spironolactone 25 mg or eplerenone 50 mg once daily if appropriate
instruct patients to stop aldosterone receptor antagonist during diarrhea, dehydration, or
while loop diuretic therapy is interrupted
avoid use of aldosterone receptor antagonists because of life-threatening hyperkalemia or renal
insufficiency if any of (ACCF/AHA Class III Harm, Level B)
serum creatinine > 2.5 mg/dL (221 mcmol/L) in men and > 2 mg/dL (176.8 mcmol/L) in
women (or estimated glomerular filtration rate < 30 mL/minute/1.73 m2)
potassium > 5 mEq/L
eplerenone (Inspra) reduces morbidity and mortality after acute myocardial infarction
complicated by heart failure (level 1 [likely reliable] evidence)
6,632 patients randomized to eplerenone (25 mg/day for 4 weeks, then up to 50 mg/day) vs.
placebo in addition to optimal medical therapy
inclusion criteria
acute myocardial infarction within 3-14 days
left ventricular dysfunction (ejection fraction < 40%)
heart failure (pulmonary congestion or third heart sound) and/or diabetes
10 patients excluded from analysis due to problems with data quality at 1 of 674 clinical sites in
37 countries
comparing eplerenone vs. placebo
mortality 14.4% vs. 16.7% (p = 0.008, NNT 44)
cardiovascular death or cardiovascular hospitalization in 26.7% vs. 30% (p = 0.002, NNT
31)
any death or hospitalization in 52.1% vs. 55.2% (p = 0.02, NNT 33)
sudden cardiac death in 4.9% vs. 6.1% (p = 0.03, NNT 84)
hospitalization for heart failure in 10.4% vs. 11.8% (p = 0.03, NNT 72)
serious hypokalemia with serum potassium < 3.5 mmol/L in 8.4% vs. 13.1% (NNT 21)
serious hyperkalemia with serum potassium > 6 mmol/L in 5.5% vs. 3.9% (NNH 62)
Reference - EPHESUS trial (N Engl J Med 2003 Apr 3;348(14):1309 full-text), correction can be
found in N Engl J Med 2003 May 29;348(22):2271, editorial can be found in N Engl J Med 2003
Apr 3;348(14):1380, commentary can be found in N Engl J Med 2003 Jul 3;349(1):88, J Fam
Pract 2003 Aug;52(8):598, CMAJ 2003 Sep 2;169(5):444 full-text, ACP J Club 2003 Sep-
Oct;139(2):34, Am Fam Physician 2003 Dec 1;68(11):2256
mortality benefits seen within first 30 days in EPHESUS trial (level 1 [likely reliable]
evidence)
based on secondary analysis of randomized trial
comparing eplerenone vs. placebo at 30 days
all-cause mortality 3.2% vs. 4.6% (p = 0.004, NNT 72)
cardiovascular mortality 3% vs. 4.4% (p = 0.003, NNT 72)
Reference - J Am Coll Cardiol 2005 Aug 2;46(3):425, commentary can be found in ACP J
Club 2006 Jan-Feb;144(1):15, Evid Based Med 2006 Feb;11(1):14, Rev Cardiovasc Med
2005 Fall;6(4):227
eplerenone associated with reduced BNP levels in patients with acute STEMI without prior heart
failure (level 3 [lacking direct] evidence)
based on nonclinical outcome from randomized trial
1,012 adults (mean age 58 years) with acute ST-elevation myocardial infarction (STEMI) and
without known prior heart failure were randomized to eplerenone once daily starting within 24
hours of symptom onset vs. placebo
eplerenone starting dose 25 mg increased to 50 mg on day 2 if serum potassium
concentration < 5 mmol/L
all patients received standard care
mean follow-up 10.5 months
brain natriuretic peptide (BNP) levels not assessed at baseline
5.1% discontinued trial due to adverse events without significant differences between groups, all
patients included in analyses

comparing eplerenone vs. placebo
elevated BNP levels at ≥ 1 month in 16% vs. 25.9% (p = 0.0003)
cardiovascular mortality 0.4% vs. 0.4% (not significant)
rehospitalization or extended hospital stay due to diagnosis of heart failure in 1.4% vs.
sustained ventricular tachycardia or ventricular fibrillation in 0% vs. 0.6% (not significant)
ejection fraction ≤ 40% at ≥ 1 month in 4% vs. 3.85% (not significant)
Reference - REMINDER trial (Eur Heart J 2014 Sep 7;35(34):2295)
see also Aldosterone antagonists for heart failure
Vasopressin antagonists
vasopressin antagonists (either V2-receptor selective or nonselective vasopressin antagonist) may be

considered in short term (ACCF/AHA Class IIb, Level B)(6)
for patients hospitalized with volume overload, including heart failure, who have persistent
severe hyponatremia and are at risk for or are having active cognitive symptoms despite water
restriction and maximization of guideline-directed medical therapy
used to improve serum sodium concentration in hypervolemic, hyponatremic states
tolvaptan (Samsca) is a vasopressin V2-receptor antagonist which produces loss of electrolytes-free
water (aquaresis) through inhibition of vasopressin in distal nephron (JAMA 2007 Mar
28;297(12):1332 full-text)
conivaptan (Vaprisol) is a nonselective vasopressin antagonist
tolvaptan may reduce fluid overload and dyspnea in patients with decompensated heart failure
but may not have long-term benefit (level 2 [mid-level] evidence)
based on 2 identical randomized trials without intention-to-treat analyses
4,133 adults with ejection fraction ≤ 40% hospitalized with acutely decompensated heart failure
received conventional therapy at discretion of attending physician and were randomized within
48 hours to tolvaptan 30 mg vs. placebo daily until end of long-term study (median 9.9 months)
postrandomization patients were assigned to trial A or trial B to meet regulatory requirement of 2
independent trials
total of 534 patients (13%) excluded from primary efficacy analysis
104 (2.5%) discontinued study medication before 7 days or hospital discharge
430 (10.4%) had missing data for ≥ 1 component of composite outcome
short-term outcomes comparing tolvaptan vs. placebo in both trials combined
greater weight loss after 1 and 7 days (generally 0.5-1 kg greater, p < 0.001 for difference
in each trial)
greater improvement in patient-assessed dyspnea after 1 day (p < 0.001 for each trial)
greater reduction in edema at day 7 (p = 0.07 for trial A, p = 0.02 for trial B)
no significant differences in patient assessed global clinical status, length of hospital stay,
or incidence of serious adverse events in either trial
long-term outcomes comparing tolvaptan vs. placebo among 3,227 patients (78%) who
completed long-term follow-up (median 9.9 months)
overall mortality 25.9% vs. 26.3% (not significant)
death from cardiovascular causes or hospitalization for heart failure in 42% vs. 40.2% (not
significant)
clinical worsening of heart failure (death, hospitalization or unscheduled visits) in 36.5%

vs. 35.8%
hypokalemia in 8% vs. 9.8% (p = 0.05, NNT 56)
thirst in 16% vs. 2.1% (p < 0.001, NNH 7)
dry mouth in 8.4% vs. 2.1% (p < 0.001, NNH 15)
cough in 5.7% vs. 7.6% (p = 0.02, NNT 53)
References - EVEREST trials
JAMA 2007 Mar 28;297(12):1332 full-text
JAMA 2007 Mar 28;297(12):1319 full-text
editorial can be found in JAMA 2007 Mar 28;297(12):1374
tolvaptan 30 mg/day may not improve dyspnea in first 24 hours despite appearing to reduce
body weight in patients with acute heart failure and volume overload (level 2 [mid-level]
evidence)
based on randomized trial without intention-to-treat analysis
250 adults (mean age 69 years) with acute heart failure and dyspnea, hospitalized in last 36
hours, and with ≥ 1 month history of heart failure treatment were randomized to tolvaptan 30
mg/ day vs. placebo for ≤ 7 days during hospitalization
all patients had extracellular volume expansion with ≥ 2 signs including jugular venous
distension, pitting edema, ascites, pulmonary congestion, and/or pulmonary rales
primary outcome was change in dyspnea score assessed at 8 and 16 hours with 7-point Likert
scale self-assessed dyspnea score (higher values indicating worse symptoms)
73% completed 3 day follow-up and were included in analysis
comparing tolvaptan vs. placebo
mean dsyspnea score at 8 hours 2.9 vs. 3 (not significant)
mean dyspnea score at 16 hours 2.7 vs. 2.7 (not significant)
mean reduction in body weight 3.54 kg vs. 2.41 kg (p = 0.006)
mean score on Likert scale 1.8 vs. 2.2 (p = 0.01) on day 3
Reference - J Am Coll Cardiol 2017 Mar 21;69(11):1409
mineralocorticoid receptor antagonist use at discharge not associated with increased all-cause
mortality in patients with acute heart failure with or without concomitant diabetes (level 2 [mid-
level] evidence)
based on retrospective cohort analysis from randomized trial
1,998 patients admitted to hospital with acute heart failure (ejection fraction ≤ 40%) from
placebo group of EVEREST trial who were followed for median 9.9 months were assessed
750 patients had concomitant diabetes
59.2% of patients with diabetes and 62.5% of patients without diabetes were prescribed
mineralocorticoid receptor antagonist (MRA) at discharge
comparing MRA use to no MRA use at discharge, no significant differences in all-cause
mortality or composite outcome of cardiovascular mortality or heart failure hospitalization,
regardless of diabetes status
Reference - Am J Cardiol 2014 Sep 1;114(5):743
Antiarrhythmic therapy (dofetilide)
dofetilide is a class III antiarrhythmic drug that selectively inhibits myocardial potassium uptake and
prolongs refractory period, has no negative inotropic effects, and does not affect cardiac conduction (N
Engl J Med 1999 Sep 16;341(12):857)
dofetilide therapy in patients with advanced systolic heart failure reduces incidence of atrial
fibrillation and hospitalizations for decompensated heart failure but does not reduce mortality
and increases serious arrhythmias (level 1 [likely reliable] evidence)
1,518 consecutive patients with New York Heart Association (NYHA) Class III or IV heart
failure and ejection fraction ≤ 35% admitted with decompensated heart failure at 34 hospitals in
Denmark randomized to dofetilide vs. placebo and followed for median 18 months
dofetilide dosing
initially 500 mcg twice daily for patients without, and 250 mcg twice daily for patients
with atrial fibrillation
after 280 patients enrolled dosing based on creatinine clearance (changed based on data
from other ongoing trials)
comparing dofetilide vs. placebo
hospitalization for decompensated heart failure 30% vs. 38% (p < 0.001, NNT 13)
percentage of patients with improvement in NYHA Class 35% vs. 30% (not significant)
mortality 41% vs. 42% (not significant)
QT prolongation requiring medication discontinuation 2% vs. 0.4% (p = 0.05)
torsade de pointes reported in 3% of patients vs. 0% (p < 0.05, NNH 33)
at 1 month, comparing dofetilide vs. placebo
among 391 patients with atrial fibrillation at baseline, conversion to sinus rhythm in 12%
vs. 1% (p = 0.05)
among 1,090 patients in sinus rhythm at baseline, atrial fibrillation developed in 2% vs.
7% (p < 0.001, NNT 20)
Reference - DIAMOND-CHF trial (N Engl J Med 1999 Sep 16;341(12):857 full-text) (full
description of methods can be found in Clin Cardiol 1997 Aug;20(8):704), commentary can be
found in N Engl J Med 2000 Jan 27;342(4):289
editorialist suggests role for dofetilide in attempts to restore sinus rhythm as a reasonable
alternative to amiodarone in patients with adequate renal function and no additional risk factors
for torsade de pointes, monitoring patients in hospital for at least 3 days after initiation of therapy
recommended, routine prophylaxis with antiarrhythmic drugs in patients with heart failure not
currently warranted (N Engl J Med 1999 Sep 16;341(12):910)
dofetilide therapy does not reduce mortality despite reduction in atrial fibrillation in patients
with recent myocardial infarction and systolic heart failure (level 1 [likely reliable] evidence)
1,510 consecutive patients admitted with myocardial infarction ≤ 7 days and ejection fraction ≤
35% at 34 hospitals in Denmark randomized to dofetilide vs. placebo and followed for median
18 months
dofetilide dosing
initially 500 mcg twice daily for patients without, and 250 mcg twice daily for patients
with atrial fibrillation
after 189 patients enrolled dosing based on creatinine clearance (changed based on data
from other ongoing trials)
comparing dofetilide vs. placebo
overall mortality 31% vs. 32% (not significant)
QT prolongation in 2.5% vs. 0.4% (p < 0.05, NNH 47)
torsade de pointes reported in 1% vs. 0% (p = 0.05)
1 death reported in dofetilide-treated patient who developed torsade de points
subgroup analysis comparing dofetilide vs. placebo

among 115 patients with atrial fibrillation or flutter at baseline, conversion to sinus rhythm
in 42% vs. 13% (p = 0.002, NNT 4) at study endpoint
among 1,395 patients without atrial fibrillation or flutter at baseline, conversion to sinus
rhythm in 0.7% vs. 1.9% at 1 year (p = 0.09)
Reference - DIAMOND-MI study (Lancet 2000 Dec 16;356(9247):2052)
review of dofetilide can be found in Expert Rev Cardiovasc Ther 2007 Jan;5(1):9
Morphine
morphine(1)
is a venodilator and a weak arterial vasodilator
suppresses feeling of air hunger
typical dose 2-4 mg IV
recommendations from professional organizations

in patients with severe dyspnea, opiates may be considered to relieve dyspnea and anxiety but
nausea and hypopnea may occur (ESC Class IIb, Level B)(7)
do not routinely offer opiates to patients with acute heart failure (NICE Acute Heart failure:
diagnosis and mangement 2014 Oct)
monitoring
alertness and ventilatory effort should be monitored frequently
have naloxone (Narcan) available in case of respiratory depression
Reference - Eur Heart J 2012 Jul;33(14):1787
morphine may be associated with increased mortality in patients with acute decompensated
heart failure, but patients given morphine more likely to be more severely ill and have active
coronary ischemia (level 2 [mid-level] evidence)
based on 2 retrospective cohort studies
147,362 hospitalizations for acute decompensated heart failure in ADHERE registry included
20,782 (14%) received morphine
at initial presentation, patients receiving morphine had higher rates of dyspnea at rest,
congestion on chest x-ray, rales, and elevated troponin
comparing in-hospital treatment patients treated with vs. without morphine
mortality 13% vs. 2.4% (p < 0.001, even after risk adjustment and exclusion of
ventilated patients)
mechanical ventilation in 15.4% vs. 2.8% (p < 0.001)
median hospital stay 5.6 vs. 4.2 days (p < 0.001)
Reference - Emerg Med J 2008 Apr;25(4):205 , commentary can be found in Emerg Med J
2009 Mar;26(3):230
2,336 patients with acute decompensated heart failure included
218 patients (9%) were treated with IV morphine
patients treated with morphine were more likely to have acute coronary syndrome,
diabetes mellitus, dyslipidemia, and higher heart rate
in-hospital mortality 11.5% in patients treated with morphine vs. 5% patients not treated
with morphine (p = 0.02 in multivariable analysis but not significant in propensity score
analysis)
Reference - Acute Card Care 2011 Jun;13(2):76
IV opiates may not be associated with reduced dyspnea in patients with cardiogenic pulmonary
edema (level 2 [mid-level] evidence)
1,052 patients (51.4% of whom received IV opiates) with cardiogenic pulmonary edema
included
opiates not associated with improvement in breathlessness as measured by visual analog scale
compared to no opiates
mortality 10.4% with opiates vs. 8.8% with no opiates (not significant)
Reference - QJM 2010 Aug;103(8):573 full-text
Inhaled bronchodilators
inhaled bronchodilator use associated with increased need for mechanical ventilation and IV
vasodilators in patients with acute decompensated heart failure and no history of chronic
obstructive pulmonary disease (COPD) (level 2 [mid-level] evidence)
based on cohort of 10,978 patients (mean age 73 years) treated in emergency departments for
acute decompensated heart failure
66.5% had no history of COPD
inhaled bronchodilator given to
14.3% patients without COPD
34.7% of patients with COPD
comparing bronchodilator vs. no bronchodilator
in patients without COPD
IV vasodilators in 28.4% vs. 16.9% (adjusted odds ratio [OR] 1.4, 95% CI 1.18-
1.67, NNH 8)
mechanical ventilation in 6% vs. 2.4% (adjusted OR 1.69, 95% CI 1.21-2.37, NNH
27)
in hospital mortality 3.4% vs. 2.6% (not significant)
in patients with COPD
in hospital mortality 2.7% vs. 3.5% (not significant)
IV vasodilators in 19.4% vs. 18.6% (not significant)
mechanical ventilation in 4.5% vs. 4.1% (not significant)
Reference - Ann Emerg Med 2008 Jan;51(1):25, editorial can be found in Ann Emerg Med 2008
Jan;51(1):35
DynaMed commentary -- study does not establish causal relationship, bronchodilator use in
patient without COPD may have been used more frequently in sicker patients or be a marker for
diagnostic uncertainty
Medications in development
ularitide
ularitide is a chemically synthesized analogue of urodilatin (a naturally occurring vasodilator) (N
Engl J Med 2017 May 18;376(20):1956)
ularitide does not improve heart failure symptoms within 48 hours (level 1 [likely reliable]
evidence) and may not reduce cardiovascular mortality in patients with acute heart failure
based on randomized trial with wide confidence interval for cardiovascular mortality
2,157 adults (mean age 68 years) with acute heart failure were randomized to ularitide 15
ng/kg/minute IV vs. placebo for 48 hours
all patients had dyspnea at rest that had worsened during previous week, BNP > 500
pg/mL or N-terminal pro-BNP > 2,000 pg/mL, evidence of heart failure on chest x-
ray, and could start study drug within 12 hours after initial evaluation
patients with dyspnea at rest for ≥ 2 hours after administration of furosemide 40 mg
IV (or equivalent) and systolic blood pressure 116-180 mm Hg were eligible for
randomization
coprimary outcomes were improvement in heart failure symptoms (patient global
assessment on 7-level Likert scale) during first 48 hours and cardiovascular death at
follow-up
median follow-up 15 months
comparing ularitide vs. placebo
improvement in heart failure symptoms within 48 hours in 48.6% vs. 47.5% (not
significant)
cardiovascular death in 21.7% vs. 21% (hazard ratio 1.03, 96% CI 0.85-1.25), not
significant but CI includes possibility of benefit or harm
median decrease in N-terminal pro-BNP at 48 hours 3,816 pg/mL vs. 2,595 pg/mL
(p < 0.001)
rehospitalization for heart failure ≤ 30 days after index hospital discharge in 7.1%
vs. 7% (not significant)
17% of randomized patients were judged ineligible after randomization (reasons for
ineligibility not specified)
in post hoc analysis excluding ineligible patients
no significant differences between groups in cardiovascular death (cardiovascular
death in 20.7% with ularitide vs. 20.8% with placebo)
improvement in heart failure symptoms at 48 hours in 48.2% with ularitide vs.
44.4% with placebo (p = 0.035, NNT 27)
most common adverse effect of ularitide was hypotension (22.4% had hypotension with
ularitide vs. 10.1% with placebo, no p value reported)
Reference - TRUE-AHF (N Engl J Med 2017 May 18;376(20):1956 full-text), editorial
can be found in N Engl J Med 2017 May 18;376(20):1987
tezosentan
tezosentan is a short-acting endothelin-receptor antagonist (endothelins are powerful
vasoconstrictors) (JAMA 2007 Nov 7;298(17):2009 full-text)
tezosentan does not appear to improve dyspnea in patients with acute heart failure despite
improvements in some hemodynamic parameters (level 2 [mid-level] evidence)
based on 2 independent, identical randomized trials without intention-to-treat analysis
1,448 patients hospitalized ≤ 24 hours for acute heart failure randomized to tezosentan 5
mg/hour IV for 30 minutes then 1 mg/hour for 24-72 hours vs. placebo
1,435 patients (mean age 70 years, 60% male) received assigned treatment and were
analyzed
no significant differences in improvement in dyspnea or rates of death, worsening heart
failure, major cardiovascular events, or combined outcomes at days 7 and 30
significant improvement (decrease) in pulmonary artery pressure and peripheral vascular

resistance recorded at various points in the trials, but hypotension more frequent with
tezosentan (22.7% vs. 14.5%, p < 0.001, NNH 12) and more frequently led to drug
discontinuation (8.3% vs. 4.7%, p = 0.003, NNH 27)
Reference - VERITAS-1 and VERITAS-2 trials (JAMA 2007 Nov 7;298(17):2009 full-
text)
relaxin
relaxin is naturally occurring peptide known to promote vasodilation and increased renal blood
flow during pregnancy (Lancet 2009 Apr 25;373(9673):1429)
serelaxin reduces dyspnea at 5 days and mortality at 180 days in patients with acute heart
failure (level 1 [likely reliable] evidence)
1,161 patients (mean age 72 years) hospitalized for acute heart failure within past 16 hours
randomized to serelaxin (recombinant human relaxin-2) 30 mcg/kg/day IV continuously
vs. placebo for 48 hours in addition to standard care
all patients had dyspnea at rest or upon minimum exertion, congestion on chest radiograph,
mild-to-moderate renal insufficiency, and systolic blood pressure > 125 mm Hg at baseline
comparing serelaxin vs. placebo
moderate-to-marked improvement in dyspnea at 6, 12, and 24 hours (assessed by 7-
level Likert scale) in 27% vs. 26% (not significant)
mean length of hospital stay 9.6 days vs. 10.5 days (p = 0.04)
mean days out of hospital at 60 days 48.3 days vs. 47.7 days (not significant)
cardiovascular death or readmission for heart failure or renal failure at 60 days in
13.2% vs. 13% (not significant)
cardiovascular mortality at 180 days 6.1% vs. 9.6% (p = 0.028, NNT 29)
all-cause mortality at 180 days 7.3% vs. 11.3% (p = 0.02, NNT 25)
serelaxin associated with greater improvement in dyspnea during days 1-5 (p = 0.007)
Reference - RELAX-AHF trial (Lancet 2013 Jan 5;381(9860):29), editorial can be found
in Lancet 2013 Jan 5;381(9860):5
no significant association between effect of serelaxin on dyspnea severity and any baseline
characteristics evaluated in prespecified secondary analysis of RELAX-AHF trial (Eur
Heart J 2013 Oct;34(40):3128 full-text)
serelaxin appears to have similar efficacy in patients with and without preserved
ejection fraction (level 2 [mid-level] evidence)
based on secondary post hoc analysis of randomized trial RELAX-AHF trial
1,091 patients with left ventricle ejection fraction (LVEF) measurements were
analyzed
281 (26%) had LVEF ≥ 50% (preserved ejection fraction)
patients with preserved ejection fraction were older and more likely to be female
no significant differences in effect of serelaxin on dyspnea severity comparing
patients with vs. without preserved ejection fractions
Reference - Eur Heart J 2014 Apr;35(16):1041
review of serelaxin can be found in Heart 2016 Jan 15;102(2):95
omecamtiv mecarbil
omecamtiv mecarbil is selective cardiac myosin activator that increases stroke volume by
prolonging myocardial systole duration without changing myocardial contraction speed (J Am
Coll Cardiol 2016 Mar 29;67(12):1444)
high-dose IV omecamtiv mecarbil may improve dyspnea at 48 hours in patients

hospitalized with acute heart failure (level 2 [mid-level] evidence)
based on randomized trial with methodologic limitations
613 patients (mean age 66 years) hospitalized with acute heart failure were randomized to
omecamtiv mecarbil (126 mg vs. 252 mg vs. 338 mg) vs. placebo 504 mL as continuous
IV infusion for 48 hours
patients were enrolled in 3 consecutive cohorts (each with matching placebo group)
targeting mean 48-hour plasma concentrations of 115 ng/mL (low-dose), 230 ng/mL
(medium-dose), and 310 ng/mL (high-dose)
enrollment was paused between cohorts to allow safety data review by independent
data monitoring committee and was resumed after committee approval
all patients had history of chronic heart failure, left ventricular ejection fraction ≤
40%, dyspnea, and elevated plasma levels of B-type natriuretic peptides
rates of hospitalization for acute heart failure in previous 12 months, presence of comorbid
paroxysmal atrial fibrillation or flutter, use of diuretics and beta blockers, and kidney
function were significantly different among individual placebo groups at baseline
dyspnea relief at 48 hours in
42% with low-dose omecamtiv mecarbil vs. 41% with placebo (not significant)
47% with medium-dose omecamtiv mecarbil vs. 46% placebo (not significant)
51% with high-dose omecamtiv mecarbil vs. 37% with placebo (p = 0.034, NNT 8)
no significant differences in median length of hospital stay or 30-day survival among
groups
Reference - ATOMIC-AHF trial (J Am Coll Cardiol 2016 Mar 29;67(12):1444 full-text)
DynaMed commentary – omecamtiv mecarbil not FDA approved for treatment of heart
failure as of April 2016
Venous thromboembolism (VTE) prophylaxis for medical patients
Anticoagulant prophylaxis for medical patients
thromboembolic prophylaxis (such as low molecular weight heparin) recommended to reduce risk of
deep venous thromboembolism and pulmonary embolism in patients not already receiving
anticoagulation if no contraindications (ESC Class I, Level B)(7)
anticoagulant prophylaxis for medical patients
assess thromboembolism and bleeding risk in medical patients prior to starting prophylaxis
against venous thromboembolism (VTE) (ACP Strong recommendation, Moderate quality
evidence)
IMPROVE Combined Risk Calculator predicts in-hospital risks
if low risk of thrombosis, do not use pharmacologic prophylaxis or mechanical prophylaxis
(ACCP Grade 1B)
guidelines recommend if risk of thrombosis outweighs risk of bleeding
patient admitted to hospital with decompensated heart failure should receive venous
thromboembolism prophylaxis with anticoagulant medication if risk-benefit ratio is
favorable (ACCF/AHA Class I, Level B)(6)
heparin or related medication is recommended for medical patients unless risk for bleeding
outweighs likely benefits (ACP Strong recommendation, Moderate quality evidence)
if increased risk for thrombosis and not at high risk for bleeding, anticoagulant prophylaxis
recommended with low-molecular-weight heparin (LMWH), low-dose unfractionated
heparin 2-3 times/day, or fondaparinux (ACCP Grade 1B)
heparin for venous thromboembolism (VTE) prophylaxis in hospitalized medical patients may
reduce risk for pulmonary embolism but increase risk for bleeding and does not appear to affect
mortality (level 2 [mid-level] evidence); LMWH and unfractionated heparin may have similar
outcomes (level 2 [mid-level] evidence)
fondaparinux (Arixtra) may prevent symptomatic and asymptomatic VTE in bedridden hospital
patients with acute medical illness (level 2 [mid-level] evidence)
see Venous thromboembolism (VTE) prophylaxis for medical patients for details
Mechanical thromboprophylaxis
guidelines differ regarding use of mechanical thromboprophylaxis

American College of Chest Physicians (ACCP) suggests graduated compression stockings or
intermittent pneumatic compression if risk factors for VTE and high risk for bleeding (ACCP
Grade 2C)
American College of Physicians (ACP) does not recommend use of graduated compression
stockings for thromboprophylaxis (ACP Strong recommendation, Moderate quality evidence) but
considers intermittent pneumatic compression a reasonable option for patients at high risk of
bleeding or in whom heparin is contraindicated
intermittent pneumatic compression may be as effective as pharmacological thromboprophylaxis
with a decreased risk of bleeding for the prevention of venous thromboembolism in hospitalized
patients (level 2 [mid-level] evidence), but no substantial evidence supports use of graduated
compression stockings
see Venous thromboembolism (VTE) prophylaxis for medical patients for details
Oxygen
oxygen recommended in patients with transcutaneous oxygen saturation < 90% or partial pressure of
oxygen in arterial blood (PaO2) < 60 mm Hg (8 kilopascals [kPa]) (ESC Class I, Level C)(7)
oxygen should not be used routinely in nonhypoxemic patients since it causes reduction in cardiac
output and vasoconstriction(5, 7)
Other management
Ultrafiltration
ultrafiltration may be considered for patients with(6)

obvious volume overload to alleviate congestive symptoms and fluid weight (ACCF/AHA Class
IIb, Level B)
refractory congestion not responding to medical therapy (ACCF/AHA Class IIb, Level C)
ultrafiltration may decrease rehospitalization at 30 days, but may not decrease rehospitalization
at 90 days and may increase risk for serious adverse events compared to adjustable IV loop
diuretics in patients with acute decompensated heart failure (level 2 [mid-level] evidence)
based on randomized trial with without adjustment for multiple comparisons

224 patients (mean age 67 years) hospitalized with acute decompensated heart failure were
randomized to adjustable ultrafiltration (AUF) vs. adjustable IV loop diuretics (ALD)
AUF (with mean fluid-removal rate of 138 mL/hour) used for mean 80 hours
ALD (with mean daily furosemide-equivalent IV loop diuretic dose 271 mg) used for
mean 100 hours
trial terminated early due to slow accrual, and no adjustments made for multiple comparisons of
prespecified secondary outcomes
heart failure event defined as heart failure hospitalization or unscheduled outpatient or
emergency room treatment with IV loop diuretics or ultrafiltration
adverse events of special interest defined as central line bloodstream infection, symptomatic
hypotension requiring intervention, bleeding requiring transfusion, drop in hemoglobin > 3 g/dL
(30 g/L), or acute coronary syndrome
comparing adjustable filtration vs. adjustable IV loop diuretics
cardiovascular rehospitalization at 30 days in 14.3% vs. 25% (p = 0.037, NNT 10)
heart failure rehospitalization
at 30 days in 9.5% vs. 20.4% (p = 0.034, NNT 10)
at 90 days in 25.7% vs. 36.1% (not significant)
adverse events
of special interest in 31% vs. 17% (p = 0.018, NNH 7)
serious, and considered related to study therapy in 14.6% vs. 5.4% (p = 0.026, NNH
10)
all cause death at 90 days in 15% vs. 13% (not significant)
estimated days to first heart failure event 62 vs. 34 (not significant)
no significant differences between groups for changes in serum creatinine up to 90 days after
randomization
Reference - AVOID HF trial JACC Heart Fail 2016 Feb;4(2):95
ultrafiltration may increase serious adverse events compared to stepped pharmacologic therapy
in patients with acute decompensated heart failure, worsening renal function, and persistent
congestion (level 2 [mid-level] evidence)
based on randomized trial without blinding
188 patients (median age 68 years) hospitalized with acute decompensated heart failure,
worsened renal function, and persistent congestion randomized to ultrafiltration vs. stepped
pharmacologic therapy and followed for 60 days
ultrafiltration (with fluid-removal rate of 200 mL/hour) used for median 40 hours
stepped pharmacologic therapy (consisting of IV diuretics) used for median 92 hours
worsened renal function defined as serum creatinine increase of ≥ 0.3 mg/dL (26.5 mcmol/L)
within 12 weeks prior to or 10 days after hospital admission for heart failure
comparing ultrafiltration vs. stepped pharmacologic therapy
mean change in serum creatinine at 96 hours +0.23 mg/dL (+20.3 mcmol/L) vs. -0.04
mg/dL (-3.5 mcmol/L) (p = 0.003)
mean change in weight at 96 hours -5.7 kg (-12.6 lb) vs. -5.5 kg (-12.1 lb) (not significant)
serious adverse events in 72% vs. 57% (p = 0.03, NNH 6)
heart failure in 33% vs. 30%
renal failure in 18% vs. 15%
pneumonia or other respiratory disorder in 11% vs. 6%
anemia or thrombocytopenia in 9% vs. 5%
sepsis, bacteremia, or cellulitis in 9% vs. 4%

gastrointestinal bleeding in 7% vs. 3%
catheter-site bleeding in 2% vs. 0%
all-cause mortality 17% vs. 13.8% (not significant)
heart failure-related hospitalization in 26% vs. 26% (not significant)
Reference - CARRESS-HF trial (N Engl J Med 2012 Dec 13;367(24):2296), editorial can be
found in N Engl J Med 2012 Dec 13;367(24):2351
ultrafiltration associated with hyponatremia for up to 30 days compared to stepped
pharmacologic therapy, but no significant differences in serum sodium levels after 30 days
and treatment-induced hyponatremia may not increase adverse events (level 2 [mid-level]
evidence)
based on cohort analysis of data from CARRESS-HF trial
all patients had serum sodium concentration analyzed
at baseline, mean serum sodium levels were 136.6 mEq/L in ultrafiltration group vs. 137.8
mEq/L in stepped pharmacologic therapy group (p = 0.03)
treatment-induced hyponatremia defined as normonatremia at admission (≥ 135 mEq/L)
with decrease during hospitalization to < 135 mEq/L
comparing ultrafiltration vs. stepped pharmacologic therapy
serum sodium concentration at 7 days 134.2 mEq/L vs. 137.1 mEq/L (p < 0.001)
serum sodium concentration at 30 days 136.6 mEq/L vs. 137.6 mEq/L (p = 0.08)
serum sodium concentration at 60 days 137.5 mEq/L vs. 138 mEq/L (not significant)
treatment-induced hyponatremia in 47% vs. 22% (p = 0.002, NNH 4)
any hyponatremia at hospital discharge associated with increased risk for composite
adverse events (all-cause death, rehospitalization, or unscheduled hospital visit) compared
to no hyponatremia, but no increased risk with treatment-induced hyponatremia compared
to no hyponatremia
Reference - Circ Heart Fail 2017 Feb;10(2):e003603, correction can be found in Circ Heart
Fail. 2017 Mar;10(3):e000016
ultrafiltration as alternative to diuresis for decompensated heart failure may reduce
rehospitalization rate (level 2 [mid-level] evidence)
200 patients hospitalized for heart failure with ≥ 2 signs of hypervolemia were randomized to
ultrafiltration vs. IV diuretics
comparing ultrafiltration vs. diuretics
rehospitalization rate at 90 days 18% vs. 32% (p = 0.037, NNT 8)
mean number of rehospitalization days per patient at 90 days 1.4 vs. 3.8 days (p = 0.022)
mean weight loss at 48 hours 5 kg vs. 3.1 kg (p = 0.001)
mean net fluid loss at 48 hours 4.6 L vs. 3.3 L (p = 0.001)
unscheduled visit rate at 90 days 21% vs. 44% (p = 0.009, NNT 5)
Reference - UNLOAD trial (J Am Coll Cardiol 2007 Feb 13;49(6):675)
ultrafiltration reported to increase fluid loss and weight loss in heart failure with volume
overload (level 3 [lacking direct] evidence)
based on randomized trial without clinical outcomes
40 patients with heart failure and evidence of volume overload were randomized to single 8-hour
session of ultrafiltration vs. usual care alone
ultrafiltration successful in 18 of 20 patients
comparing ultrafiltration vs. usual care
fluid removal over 24 hours was 4,650 mL vs. 2,838 mL (p = 0.001)

weight loss at 24 hours 2.5 kg vs. 1.86 kg (not significant)
Reference - J Am Coll Cardiol 2005 Dec 6;46(11):2043
review of ultrafiltration therapy for heart failure: balancing likely benefits against possible risks can be
found in Clin J Am Soc Nephrol 2016 Aug 8;11(8):1463
Noninvasive ventilation
noninvasive positive pressure ventilation (NPPV) refers to provision of ventilatory support through
upper airway via mask or similar device without artificial endotracheal airway
positive pressure ventilation reduces preload (increased intrathoracic pressure and decreased venous
return)(1)
European Society of Cardiology (ESC) recommendations for noninvasive ventilation (ESC Class IIa,
Level B)(7)
consider noninvasive ventilation (for example, continuous positive airway pressure) in patients
with respiratory distress (respiratory rate > 25 breaths/minute, transcutaneous oxygen saturation
< 90%) and start as early as possible to improve breathlessness and reduce rate of mechanical
endotracheal intubation
use noninvasive positive pressure ventilation with caution in hypotensive patients and monitor
blood pressure regularly due to potential to reduce blood pressure
British Thoracic Society (BTS) recommendations for noninvasive ventilation
continuous positive airway pressure (CPAP) shown to be effective for patients with cardiogenic
pulmonary edema who remain hypoxic despite maximal medical treatment (BTS Grade B)
reserve NPPV for patients not responding to CPAP
Reference - BTS noninvasive ventilation in acute respiratory failure (Thorax 2002
Mar;57(3):192 PDF), commentary can be found in Emerg Med J 2002 Sep;19(5):435 PDF,
Thorax 2002 Nov;57(11):1002 PDF
noninvasive ventilation may improve respiratory distress but effect on mortality or need for
intubation unclear (level 2 [mid-level] evidence)
based on inconsistent findings in 1 large randomized trial and 7 systematic reviews
noninvasive ventilation may improve respiratory distress but may not improve mortality
compared to standard oxygen therapy (level 2 [mid-level] evidence)
based on randomized trial with wide confidence intervals and differences in dyspnea score
that may not be clinically important (largest trial in Cochrane review below)
1,156 patients (mean age 78 years) with acute cardiogenic pulmonary edema randomized
to 1 of 3 groups
supplemental oxygen via variable-delivery oxygen mask with reservoir to maintain
oxygen saturations > 92%
continuous positive airway pressure (CPAP) started at 5 cm H2O and increased to
maximum of 15 cm H2O
NPPV started at inspiratory positive airway pressure of 8 cm H2O (maximum of 20
cm H2O) and expiratory positive airway pressure of 4 cm H2O (maximum of 10 cm
H2O)
87 patients excluded after randomized due to ineligibility or previous recruitment
mean duration of therapy 2.2 hours for CPAP and 2 hours for NIPPV
dyspnea score rated 0-10 (10 signifying maximal breathlessness), mean dyspnea score at
baseline 8.9
comparing noninvasive ventilation (CPAP or NIPPV) vs. oxygen
7-day mortality 9.5% vs. 9.8% (not significant, 95% CI for absolute difference
-3.6% to +4.7%)
30-day mortality 15.2% vs. 16.4% (not significant, 95% CI for absolute difference
-5.9% to +5.1%)
intubation within 7 days in 2.9% vs. 2.8% (not significant)
admission to critical care unit in 45.2% vs. 40.5% (p = 0.15)
myocardial infarction in 51.9% vs. 50.5% (not significant)
mean length of hospital stay 11.4 vs. 10.5 days (p = 0.1)
mean change in dyspnea score at 1 hour 4.6 vs. 3.9 (p = 0.008)
no significant differences comparing CPAP vs. NIPPV in any clinical outcome
Reference - Three Interventions in Cardiogenic Pulmonary Oedema (3CPO) trial (N Engl J
Med 2008 Jul 10;359(2):142), commentary can be found in N Engl J Med 2008 Nov
6;359(19):2068, ACP J Club 2008 Dec 16;149(6):9, cost-effectiveness analysis can be
found in Health Technol Assess 2009 Jul;13(33):1
noninvasive ventilation may reduce mortality and need for intubation in patients with
acute cardiogenic pulmonary edema (level 2 [mid-level] evidence)
based on 6 systematic reviews of randomized trials (most with methodologic limitations)
Cochrane review of 32 randomized or quasi-randomized trials evaluating noninvasive
positive pressure ventilation (NPPV) in 2,916 adults with acute or acute-on-chronic
cardiogenic pulmonary edema
NPPV included continuous positive airway pressure or bilevel NPPV
most trials had ≥ 1 limitation including
unclear or inadequate allocation concealment
unclear or lack of blinding
lack of intention-to-treat analysis
subgroup analysis
comparing NPPV plus standard medical care to standard medical care alone
NPPV associated with
decreased hospital or 7-day mortality in analysis of 21 trials with 2,263
adults
risk ratio (RR) 0.72 (95% CI 0.55-0.94)
NNT 14-105 with 16% in-hospital or 7-day mortality in standard
medical care group
decreased endotracheal intubation in analysis of 22 trials with 1,261
adults
RR 0.52 (95% CI 0.36-0.75)
NNT 7-16 with endotracheal intubation in 25% of standard
medical care group
shorter intensive care unit stay (mean difference -0.89 days, 95% CI
-1.33 to -0.45 days) in analysis of 6 trials with 222 adults
no significant differences in length of hospital stay or incidence of acute
myocardial infarction during or after NPPV
Reference - Cochrane Database Syst Rev 2013 May 31;(5):CD005351
systematic review of 31 randomized trials evaluating CPAP and/or bilevel positive airway
pressure (BiPAP) in 2,887 patients (aged 51-92 years) with acute cardiogenic pulmonary
edema
standard care was oxygen, diuretics, nitrates and supportive care
comparing CPAP vs. standard therapy (15 trials)
CPAP associated with
reduced in-hospital mortality overall in analysis of 13 trials with 1,369
patients
risk ratio (RR) 0.64 (95% CI 0.44-0.92)
NNT 12-84 assuming 15% mortality in standard therapy groups
nonsignificantly reduced in-hospital mortality in analysis restricted to
trials with ≥ 50% patients with cardiogenic pulmonary edema due to
acute myocardial infarction or ischemia (RR 0.43 95% CI 0.17-1.07)
reduced need for intubation in analysis of 15 trials with 1,505 patients
RR 0.44 (95% CI 0.32-0.6)
NNT 10-17 assuming intubation in 15% of standard therapy
groups
no significant difference in mortality in analysis restricted to trials with ≤ 10%
patients with acute myocardial infarction or ischemia (includes 3CPO trial
summarized above)
no significant difference in incidence of new myocardial infarction in analysis
of 4 trials with 825 patients
comparing BiPAP vs. standard therapy (10 trials)
BiPAP associated with
nonsignificantly reduced in-hospital mortality in analysis restricted to
trials with ≥ 50% patients with cardiogenic pulmonary edema due to
acute myocardial infarction or ischemia (RR 0.43 95% CI 0.17-1.07)
reduced need for intubation in analysis of 10 trials with 1,153 patients
RR 0.54 (95% CI 0.33-0.86)
NNT 10-48 assuming intubation in 15% of standard therapy
groups
no significant difference in mortality in analysis of 9 trials with 1,091 patients
no significant difference in incidence of new MI in analysis of 6 trials with
1,001 patients
no significant differences in mortality, intubation, or new myocardial infarction in
trials comparing CPAP vs. BiPAP (16 trials)
Reference - Ann Intern Med 2010 May 4;152(9):590, correction can be found in
Ann Intern Med 2010 Jul 6;153(1):67
similar results reported in systematic review of 15 randomized trials comparing
noninvasive ventilation vs. conventional oxygen therapy or another noninvasive
ventilation modality in patients with acute cardiogenic pulmonary edema (JAMA 2005
Dec 28;294(24):3124)
similar results reported in systematic review of 17 randomized trials (Crit Care
2006;10(2):R69 full-text)
similar results reported in systematic review of 23 randomized trials (Lancet 2006 Apr
8;367(9517):1155)
similar results reported in systematic review of 11 randomized trials (Ann Emerg Med
2006 Sep;48(3):260)
similar results reported in systematic review of 17 randomized trials (Crit Care Med 2015
Apr;43(4):880), editorial can be found in Crit Care Med 2015 Apr;43(4):927
monitor clinical status of patient, arterial blood gases, and oxygen saturation
clinical improvement and patient stability are most important factors for determining timing of NPPV
withdrawal
see Noninvasive positive pressure ventilation (NPPV) in adults for details
Intubation
intubation recommended if unable to noninvasively manage respiratory failure leading to (ESC Class I,
Level C)(7)
hypoxemia (partial pressure of oxygen in arterial blood < 60 mm Hg [8 kilopascal])
hypercapnia (partial pressure of carbon dioxide in arterial blood > 50 mm Hg [6.65 kilopascal])
acidosis (pH < 7.35)
Invasive hemodynamic monitoring
American College of Cardiology Foundations and American Heart Association (ACCF/AHA)

recommendations(6)
perform invasive hemodynamic monitoring with pulmonary artery catheter to guide therapy in
patients who have respiratory distress or clinical evidence of impaired perfusion in whom
adequacy or excess of intracardiac filling pressures cannot be determined from clinical
assessment (ACCF/AHA Class I, Level C)
invasive hemodynamic monitoring may be useful for carefully selected patients with acute heart
failure with persistent symptoms despite empiric adjustment of standard therapies if any of
(ACCF/AHA Class IIa, Level C)
fluid status, perfusion, or systemic or pulmonary vascular resistances is uncertain
systolic blood pressure remains low or is associated with symptoms despite initial therapy
renal function worsens with therapy
parenteral vasoactive agents are needed
consideration for mechanical circulatory support or transplantation
routine use of invasive hemodynamic monitoring NOT recommended in normotensive patients
with acute decompensated heart failure and congestion with symptomatic response to diuretics
and vasodilators (ACCF/AHA Class III No Benefit, Level B)
intra-arterial line suggested in patients with hypotension and persistent symptoms despite
treatment (ESC Class IIa, Level C)
consider pulmonary artery catheter in patients with symptoms refractory to pharmacologic
therapy, particularly in patients with hypotension and hypoperfusion (ESC Class IIb, Level C)
pulmonary artery catheterization may increase adverse events (level 2 [mid-level] evidence) and
does not reduce mortality or length of hospitalization (level 1 [likely reliable] evidence)
433 patients with severe symptomatic recurrent heart failure at 26 sites randomized to therapy
guided by clinical assessment and pulmonary artery catheter vs. guided by clinical assessment
alone
comparing pulmonary artery catheter vs. control group
mean total days hospitalized 8.7 vs. 8.3
mortality within 30 days 4.7% vs. 5%
mortality within 6 months 20% vs. 17%
at least 1 adverse event in 21.9% vs. 11.5% (p = 0.04, NNH 9)
pulmonary artery catheter infection in 1.9% vs. 0% (p = 0.03, NNH 52)
Reference - JAMA 2005 Oct 5;294(13):1625, editorial can be found in JAMA 2005 Oct
5;294(13):1693, commentary can be found in JAMA 2006 Mar 8;295(10):1121
Discharge and follow-up

recommendations(6)
use of performance improvement systems and/or evidence-based systems of care recommended
in hospital and early postdischarge outpatient setting to identify appropriate heart failure patients
for guideline-directed medical therapy, provide clinicians with useful reminders, and assess
clinical response (ACCF/AHA Class I, Level B)
issues to address throughout hospitalization, before discharge, at first postdischarge visit, and in
subsequent follow-up visits, include (ACCF/AHA Class I, Level B)
initiation of guideline-directed medical therapy if not previously established and not
contraindicated
precipitant causes of heart failure
barriers to optimal care transitions and limitations in postdischarge support
assessment of volume status and supine/upright hypotension with adjustment of therapy as
appropriate
titration and optimization of chronic oral heart failure therapy
assessment of renal function and electrolytes
assessment and management of comorbid conditions
reinforcement of heart failure education, self-care, emergency plans, and need for
adherence
consideration for palliative or hospice care in selected patients
multidisciplinary heart failure disease-management programs are recommended for patients at
high risk for hospital readmission (ACCF/AHA Class I, Level B)
to facilitate implementation of guideline-directed medical therapy
to address different barriers to behavioral change
to reduce risk of subsequent rehospitalization for heart failure
reasonable to schedule early telephone follow-up (within 3 days) and early follow-up visit
(within 7-14 days) after discharge (ACCF/AHA Class IIa, Level B)
reasonable to use clinical risk prediction tools and/or biomarkers to identify patients at higher
risk for postdischarge clinical events (ACCF/AHA Class IIa, Level B)
discharge from hospital with higher rate of early follow-up (within 7 days) associated with
reduced risk of readmission within 30-days (level 2 [mid-level] evidence)
30,136 patients ≥ 65 years old hospitalized with heart failure and discharged to home from
hospitals participating in quality improvement program were analyzed
median length of stay was 4 days, and 21.3% of patients were readmitted within 30 days
at hospital level, median percentage of patients who had early follow-up (within 7 days) after
discharge was 38.3%
30-day readmission rates per quartile of early follow-up
23.3% for patients in first (lowest) quartile
20.5% for patients in second quartile (risk-adjusted hazard ratio [HR] 0.85, 95% CI 0.78-
0.93 vs. lowest quartile)
20.5% for patients in third quartile (risk-adjusted HR 0.87, 95% CI 0.78-0.96 vs. lowest
quartile)
20.9% for patients in fourth quartile (risk-adjusted HR 0.91, 95% CI 0.83-1 vs. lowest
quartile)
Reference - JAMA 2010 May 5;303(17):1716
Complications and Prognosis

General complications
respiratory failure with need for mechanical ventilation(7)

cardiac arrhythmias(5,7)
end-organ damage
heart failure-related myopathy (Eur Heart J 1999 Aug;20(16):1191 PDF)
hypoxic liver injury (Mayo Clin Proc 2006 Sep;81(9):1232)
venous congestion associated with worsening renal function in patients with advanced
145 patients admitted with advanced decompensated heart failure and treated with
intensive medical therapy guided by pulmonary artery catheter evaluated
worsening renal function
developed in 40%
associated with greater central venous pressure on admission (p < 0.001)
associated with greater central venous pressure after intensive medical therapy (p =
0.04)
occurred less frequently with central venous pressure < 8 mm Hg (p = 0.01)
Reference - J Am Coll Cardiol 2009 Feb 17;53(7):589 full-text, editorial can be found in J
Am Coll Cardiol 2009 Feb 17;53(7):597, commentary can be found in J Am Coll Cardiol
2009 Aug 11;54(7):661
Cardiorenal syndrome
reported to occur in about 35% of patients admitted to hospital with acute decompensated heart failure
cardiorenal syndrome associated with increased mortality
generally defined as pathophysiologic disorder of heart and kidneys in which acute or chronic
dysfunction of 1 organ has ability to initiate and perpetuate acute or chronic dysfunction in the
other, but no consensus of precise definition
proposed classification includes the following subtypes
type 1 - acute worsening of cardiac function (for example, decompensation of chronic
heart failure or cardiogenic shock) causing acute kidney injury

type 2 - chronic abnormality in cardiac function (for example, chronic heart failure)
causing progressive chronic kidney disease
type 3 - acute worsening of renal function (for example, acute kidney failure or
glomerulonephritis) causing acute cardiac dysfunction (for example, heart failure,
arrhythmia)
type 4 - chronic kidney disease (for example, chronic glomerular disease) causing
decreased cardiac function, cardiac hypertrophy, and/or increased risk of adverse
cardiovascular events
type 5 - systemic condition (for example, sepsis, diabetes) causing both cardiac and renal
dysfunction
most often refers to acute kidney injury in setting of acute on chronic decompensated heart
failure (cardiorenal syndrome type 1)
References - Cardiovasc Hematol Disord Drug Targets 2014;14(3):170, J Am Coll Cardiol 2008
Nov 4;52(19):1527 full-text , Cardiorenal Med 2014 Dec;4(3-4):176 full-text , Nephrol Dial
Transplant 2010 Jun;25(6):1777 full-text
has unclear pathophysiology, but thought to involve several mechanisms that may include
complex bidirectional neurohormonal and hemodynamic interactions between the heart and
kidney possibly involving
chronic sodium and volume balance
inflammation via tumor necrosis factor alpha
nitric oxide metabolism
oxidative injury
neurohormonal activation that may include effects mediated through
renin-angiotensin-aldosterone system (RAAS)
sympathetic nervous system
endothelin
arginine vasopressin
neurohormonal activation that may influence
cardiac afterload and/or contractility which may affect cardiac output
volume status
sympathetic nervous system activation
oxidative stress and decrease in cardiac output and renal blood flow, which may result in
kidney dysfunction
kidney dysfunction that may result in factors that may cause cardiac dysfunction, including
increase in sympathetic nervous system activity
oxidative stress
increase in RAAS
treatment of cardiorenal syndrome
no consensus for specific treatment modalities
treatment individualized based on underlying pathophysiologic processes
general treatment considerations may include
type 1
accurate assessment of volume status
treatment of intravascular volume overload with diuretics and consideration of
ultrafiltration in diuretic-resistant patients
mobilization of fluid in third spaces including use of compression therapy and
removal of ascites
in the absence of volume overload consider combination of vasodilator
therapy and positive inotropic agents
for refractory patients consider mechanical circulatory support or eligibility
for cardiac transplantation
type 2
use of medications that improve the natural history of chronic heart failure
(for example, angiotensin converting enzyme inhibitors and beta blockers)
optimal management of sodium and extracellular fluid volume via use of low-
sodium diet and diuretics
avoidance of nephrotoxic agents (for example, iodinated contrast media,
nonsteroidal anti-inflammatory drugs)
type 3 - avoidance of hypervolemia
type 4 - evidence-based therapies which may reduce progression of chronic kidney
disease
type 5 - treatment of the primary illness (for example, sepsis, diabetes)
References - Nephrol Dial Transplant 2010 Jun;25(6):1777 full-text , Cardiorenal Med
2014 Dec;4(3-4):176 full-text
randomized trials in patients with cardiorenal syndrome include CARRESS-HF and ROSE
trials
review of acute decompensated heart failure and cardiorenal syndrome can be found in Crit Care Med
2008 Jan;36(1 Suppl):S75
Prognosis
Prediction rules
multivariable risk scores(6)

validated multivariable risk scores can be useful to estimate subsequent risk of mortality in
ambulatory or hospitalized patients with heart failure (ACCF/AHA Class IIa, Level B)
risk scores for patients with acutely decompensated heart failure include
ADHERE Classification and Regression Tree (CART) Model (JAMA 2005 Feb
2;293(5):572), commentary can be found in JAMA 2005 May 25;293(20):2467, ACP J
Club 2005 Jul-Aug;143(1):25
American Heart Association Get With The Guidelines Score (Circ Cardiovasc Qual
Outcomes 2010 Jan;3(1):25 full-text poster PDF)
EFFECT Risk Score (JAMA 2003 Nov 19;290(19):2581), commentary can be found in
ACP J Club 2004 May-Jun;140(3):80 online calculator can be found at Canadian
Cardiovascular Outcomes Research Team
ESCAPE Risk Model and Discharge Score (J Am Coll Cardiol 2010 Mar 2;55(9):872)
OPTIMIZE HF Risk-Prediction Nomogram (Circ Heart Fail 2011 Sep;4(5):628 full-text)
ADHERE risk tree validated for predicting in-hospital mortality
based on cohort of 65,275 hospital records of adults presenting to United States hospitals with
acutely decompensated heart failure, retrospective derivation cohort of 33,046 hospitalization
episodes from 2001 to 2003, and prospective validation cohort of 32,229 hospitalization episodes
from March to July 2003
in patients with blood urea nitrogen (BUN) < 43 mg/dL (30.7 mmol/L)
if systolic blood pressure 115 mm Hg or higher, in-hospital mortality 2.14% in derivation
cohort, and 2.31% in validation cohort
if systolic blood pressure < 115 mm Hg, in-hospital mortality 5.49% in derivation cohort,
and 5.67% in validation cohort
in patients with BUN 43 mg/dL (30.7 mmol/L) or higher
if systolic blood pressure 115 mm Hg or higher, in-hospital mortality 6.41% in derivation
cohort, and 5.63% in validation cohort
if systolic blood pressure < 115 mm Hg
if serum creatinine < 2.75 mg/dL (243.1 mcmol/L), in-hospital mortality 12.42% in
derivation cohort, and 13.23% in validation cohort
if serum creatinine 2.75 mg/dL (243.1 mcmol/L) or higher, in-hospital mortality
21.94% in derivation cohort, and 19.76% in validation cohort
Reference - JAMA 2005 Feb 2;293(5):572, commentary can be found in JAMA 2005 May
25;293(20):2467, ACP J Club 2005 Jul-Aug;143(1):25, summary can be found in Am Fam
Physician 2007 Apr 15;75(8):1231 full-text
alternative validated predictive index (EFFECT rule) for mortality after hospital admission for
heart failure
online calculator can be found at Canadian Cardiovascular Outcomes Research Team
derived from Enhanced Feedback For Effective Cardiology Treatment (EFFECT) study
details of predictive index
based on retrospective cohort of 4,031 community-dwelling patients presenting to
Canadian hospitals with heart failure, derivation cohort of 2,624 patients from 1999 to
2001, and validation cohort of 1,407 patients from 1997 to 1999
score derived from factors easily determined within hours of hospital admission
score derivation varies slightly for 30-day prediction and 1-year prediction
1 point for each year of age
systolic blood pressure (in mm Hg) for 30-day score is -60 points if 180 or higher,
-55 points if 160-179, -50 points if 140-159, -45 points if 120-139, -40 points if 100-
119, -35 points if 90-99, - 30 points if < 90; subtract 10 more points for 1-year score
add 1 point for each mg/dL (0.714 mmol/L) units of blood urea nitrogen (BUN) up
to maximum 60
add 10 points if sodium < 136 mEq/L
add 10 points if cerebrovascular disease
dementia adds 20 points for 30-day score, 15 points for 1-year score
add 10 points if chronic obstructive pulmonary disease (COPD)
hepatic cirrhosis adds 25 points for 30-day score, 35 points for 1-year score
add 15 points if cancer
hemoglobin < 10 g/dL adds 10 points to 1-year score (not used in 30-day score)
mortality rates predicted by scores
score 60 or less predicts 0.4%-0.6% mortality at 30 days and 2.7%-7.8% mortality at
1 year
score 61-90 predicts 3.4%-4.2% mortality at 30 days and 12.9%-14.4% mortality at
1 year
score 91-120 predicts 12.2%-13.7% mortality at 30 days and 30.2%-32.5% mortality
at 1 year
score 121-150 predicts 26%-32.7% mortality at 30 days and 55.5%-59.3% mortality
at 1 year
score > 150 predicts 50%-59% mortality at 30 days and 74.7%-78.8% mortality at 1
year
Reference - JAMA 2003 Nov 19;290(19):2581, commentary can be found in ACP J Club
2004 May-Jun;140(3):80, summary can be found in Am Fam Physician 2007 Apr
15;75(8):1231 full-text
addition of Barthel Index to EFFECT rule appears to improve prediction of 30-day mortality in
elderly patients with acute heart failure in emergency department (level 2 [mid-level] evidence)
based on validation cohort study with limited data regarding performance
1,065 elderly patients (mean age 80 years) with acute heart failure in emergency department
were evaluated for prediction of mortality at 30 days using
Barthel Index (severe if ≤ 60 points, not severe if > 60 points)
EFFECT rule (high-to-very-high risk if > 120 points, intermediate risk if 91-120 points,
and low-to-very-low risk if ≤ 90 points)
combination of Barthel Index and EFFECT rule
30-day mortality 5.1%
combination of Barthel Index and EFFECT rule associated with greater discrimination for
prediction of 30-day mortality (p = 0.02)
Reference - J Am Geriatr Soc 2012 Mar;60(3):493
Ottawa Heart Failure Risk Scale predicts serious adverse events within 30 days of emergency
department index visit in patients with acute heart failure (level 1 [likely reliable] evidence)
based on prognostic cohort study
1,100 patients (mean age 77 years) with acute heart failure in emergency department were
evaluated for prediction of serious adverse events (SAE) at 30 days using Ottawa Heart Failure
Risk Scale (OHFRS)
Ottawa score risk categories for SAE within 14 days (range 0-15 points)
0 points = low risk
1 or 2 points = medium risk
3 or 4 points = high risk
≥ 5 points = very high risk
serious adverse events defined as death from any cause ≤ 30 days from index emergency
department visit, or any of the following at ≤ 14 days from initial visit
admission to monitored hospital unit (such as intensive care)
endotracheal intubation or noninvasive ventilation requirement after admission
myocardial infarction
major procedure (unplanned percutaneous coronary intervention, coronary artery bypass
graft, other cardiac surgery, or new hemodialysis)
relapse and hospital readmission (in patients discharged after initial emergency department
visit)
serious adverse events at ≤ 30 days from index emergency department visit in 15.5%
comparing OHFRS with threshold > 1 point vs. actual practice for predicting serious adverse
events
overall
sensitivity 91.8% vs. 71.8% (overall)
specificity 24.9% vs. 45.5% (overall)
among patients with B-type natriuretic peptide measurements (62.1%)
sensitivity 95.8% vs. 69.8%
specificity 13.6% vs. 41.1%

Reference - Acad Emerg Med 2017 Mar;24(3):316
Brigham and Women’s Hospital (BWH) prediction rule may predict risk for major
complications of death (level 2 [mid-level] evidence)
based on derivation cohort study without validation
435 patients admitted nonelectively with heart failure 1993-1994 were analyzed
77 (18%) had major complication or death
4 risk factors for major complication or death were
initial systolic blood pressure ≤ 90 mm Hg
respiratory rate > 30 breaths/minute on hospital admission
serum sodium level ≤ 135 mmol/L (135 mEq/L)
ST-T wave changes on initial electrocardiogram (ECG) not known to be old or attributable
to digoxin
risk for major complication or death
if 0 risk factors 6%
if 1 risk factor 17%
no patient had 4 risk factors
Reference - Arch Intern Med 1996 Sep 9;156(16):1814
4 prediction rules (ADHERE tree, ADHERE logistic regression, EFFECT rule, BWH rule) all
predicted in-hospital and 30-day mortality rates in retrospective cohort of 33,533 adults admitted for
heart failure from emergency department to Pennsylvania hospitals in 1999 (Ann Emerg Med 2007
Aug;50(2):127)
Mortality risk
1-year mortality 35.8% following hospitalization for heart failure in older patients (level 2 [mid-
level] evidence)
patients ≥ 65 years old on Medicare who survived hospitalization for heart failure, acute
myocardial infarction, or pneumonia were followed for up to 1 year
972,339 patients had 1,462,453 hospitalizations for heart failure
1-year mortality 35.8%
compared to general Medicare population, patients with heart failure had increased mortality
at 30 days (adjusted standardized incidence ratio 17.8, 95% CI 17.7-18)
at 1 year (adjusted standardized incidence ratio 6.3, 95% CI 6.3-6.3)
Reference - BMJ 2015 Feb 5;350:h411 full-text
reported mortality risk following heart failure in 1,206 incident heart failure hospitalizations in United
States
10.4% at 30 days
22% at 1 year
42.3% at 5 years
Reference - Am J Cardiol 2008 Apr 1;101(7):1016
high mortality after hospitalization for heart failure
high 5-year mortality reported after hospitalization for acute heart failure
2,445 Worcester, Massachusetts area residents discharged from 11 area hospitals after
confirmed acute heart failure in 2000 and followed to 2005
mean age 76 years, about 75% had prior diagnosis of heart failure
mortality was 37.3% at 1 year and 78.5% at 5 years
Reference - Arch Intern Med 2007 Mar 12;167(5):490
high mortality reported in cohort of patients with first hospitalization for heart failure
38,702 consecutive patients with first-time admissions for heart failure evaluated
30-day case fatality was 11.6%, ranging from 2.3% among younger patients without
comorbidity to 23.8% among older patients with comorbidity
1-year case fatality was 33.1%, ranging from 7.6% among younger patients without
comorbidity to 60.7% among older patients with comorbidity
Reference - Arch Intern Med 2002 Aug 12/26;162(15):1689, commentary can be found in
Arch Intern Med 2003 Mar 24;163(6):737
survival following first hospitalization improving since 1986 for heart failure in Scotland
based on population study of 5.1 million people from 1986 to 2003
116,556 people (2.3%) had first hospital discharge for heart failure
median survival comparing 1986 vs. 2003
1.33 vs. 2.34 years in men
1.32 vs. 1.79 years in women
Reference - Circulation 2009 Feb 3;119(4):515
risk factors for mortality include low blood pressure (< 120 mm Hg), precipitating ischemia, and
based on cohort study (OPTIMIZE-HF study)
48,612 patients hospitalized with acute heart failure (51% had preserved left ventricular ejection
fraction) at 259 United States hospitals
1,834 in-hospital deaths (3.8%) occurred
29,814 (61.3%) had ≥ 1 precipitating factor
pneumonia/respiratory process (15.3%)
ischemia (14.7%)
arrhythmia (13.5%)
in-hospital mortality rates stratified by systolic blood pressure at admission
7.2% if < 120 mm Hg
3.6% if 120-139 mm Hg
2.5% if 140-161 mm Hg
1.7% if > 161 mm Hg
increased in-hospital mortality significantly associated with
pneumonia
ischemia
postdischarge mortality (60-90 days) evaluated in 5,791 patients
postdischarge mortality rates stratified by systolic blood pressure at admission
14% if < 120 mm Hg
8.4% if 120-139 mm Hg
6% if 140-161 mm Hg
5.4% if > 161 mm Hg
increased 60-90 day mortality significantly associated with
ischemia
References
JAMA 2006 Nov 8;296(18):2217, editorial can be found in JAMA 2006 Nov
8;296(18):2259, commentary can be found in JAMA 2007 Feb 28;297(8):807
Arch Intern Med 2008 Apr 28;168(8):847
in patients with acute decompensated heart failure, Chronic Kidney Disease Epidemiology
Collaboration (CKD-EPI) creatinine equation and Modification of Diet in Renal Disease
(MDRD) study equation may have similar performance for prediction of all-cause mortality
1,805 patients (mean age 80 years) with acute decompensated heart failure (58% with preserved
ejection fraction) were analyzed
mean estimated glomerular filtration rate (GFR) 51 mL/minute/1.73 m2 with CKD-EPI equation
vs. 55 mL/minute/1.73 m2 with MDRD-4 equation (p < 0.001)
1-year all-cause mortality 23.7%
decreased estimated GFR by CKD-EPI and MDRD equations each associated with increased risk
of all-cause mortality in both patients with preserved and reduced ejection fractions (p < 0.001
for each)
no significant differences between equations in predictive performance for all-cause mortality
Reference - RICA study (Int J Clin Pract 2015 Aug;69(8):829)
lower systolic blood pressure associated with increased risk of all-cause mortality and
cardiovascular hospitalization in patients with acute heart failure
2,061 patients admitted to hospital with acute heart failure (ejection fraction ≤ 40%) from
placebo group of EVEREST trial were followed for median 9.9 months
all-cause mortality by baseline systolic blood pressure (SBP) (p < 0.001 for trend)
38.9% of 537 patients with SBP 82-105 mm Hg
22% of 523 patients with SBP 120-130 mm Hg
cardiovascular hospitalization by baseline SBP (p < 0.001 for trend)
49.9% with SBP 82-105 mm Hg
43.3% with SBP 106-119 mm Hg
32.8% with SBP 120-130 mm Hg
29.7% with SBP 131-202 mm Hg
Reference - Am Heart J 2013 Feb;165(2):216
in-hospital hypotensive episode associated with increased mortality in patients with acute
based on cohort analysis of data from ASCEND-HF trial
7,141 patients with acute decompensated heart failure who were randomized to nesiritide vs.
placebo were assessed
21.8% had episode of in-hospital hypotension, of whom 73.1% were symptomatic and 26.9%
were asymptomatic
compared to patients without hypotension, in-hospital hypotensive episode associated with
increased 30-day mortality (adjusted hazard ratio 2.03, 95% CI 1.57-2.61)

factors associated with increased risk of in-hospital hypotensive episode included
randomization to nesiritide (odds ratio [OR] 1.98, 95% CI 1.76-2.23)
chronic metolazone therapy (OR 1.74, 95% CI 1.17-2.6)
temperature > 36.4 degrees C (> 97.5 degrees F) (OR per 1 degree C increase 1.38, 95%
CI 1.12-1.72)
baseline orthopnea (OR 1.31, 95% CI 1.13-1.52)
baseline S3 gallop (OR 1.21, 95% CI 1.06-1.4)
increased age (OR per 10 years over age 60 years 1.15, 95% CI 1.07-1.22)
heart rate ≤ 75 beats per minute (OR per 5-beat decrease 1.1, 95% CI 1.04-1.17)
Reference - Circ Heart Fail 2014 Nov;7(6):918
lower total serum cholesterol and triglyceride levels each associated with increased mortality in
patients hospitalized for worsening heart failure
based on prognostic cohort study
3,957 patients hospitalized for worsening heart failure with ejection fractions ≤ 40% from
randomized trial comparing oral tolvaptan vs. placebo were stratified to quartiles for baseline
total cholesterol and triglyceride levels
baseline total cholesterol and triglyceride levels measured within 48 hours of hospital
admission
samples collected were not required to be fasting
median duration of follow-up was 9.9 months
low serum total cholesterol significantly associated with increased all-cause mortality and
composite of cardiovascular mortality or hospitalization for heart failure
low baseline triglyceride levels significantly associated with increased all-cause mortality
Reference - Am J Cardiol 2013 Feb 15;111(4):574
chronic kidney disease and anemia associated with increased in-hospital mortality in 955 patients
hospitalized with heart failure (BMC Nephrology 2006 Mar 6;7:3 full-text)
COPD associated with increased 5-year mortality in cohort of 799 patients hospitalized with first
episode of heart failure in France (Am J Cardiol 2008 Feb 1;101(3):353)
cardiogenic pulmonary edema requiring mechanical ventilation associated with high mortality,
but relatively good functional status in survivors at 3 months
79 patients > 75 years old with cardiogenic pulmonary edema requiring mechanical ventilation
evaluated
26.6% in-hospital mortality
58 survivors were followed for mean 23 months
among survivors, 69% survival at 1 year and at 3 months 87% lived at home, 82% able to bathe
themselves, 62% could walk at least 1 block, and 61% could climb 1 flight of stairs
Reference - Crit Care Med 2001 Apr;29(4):891
elevated brain natriuretic peptide (BNP) levels may predict death and readmission after heart
failure exacerbation
203 patients ≥ 65 years old admitted due to cardiogenic pulmonary edema with B-type natriuretic
peptide (BNP) > 100 pg/mL evaluated
31 (15.3%) died and 44 (21.7%) readmitted for heart failure in 6 months after discharge
mean BNP levels in patients with death or readmission were > 1,000 pg/mL at initial
admission and almost 800 pg/mL at initial discharge

mean BNP levels in patients without death or readmission were about 600 pg/mL at initial
admission and about 300 pg/mL at initial discharge
Reference - Am J Geriatr Cardiol 2006 Jul-Aug;15(4):202
elevated BNP levels associated with poorer prognosis (death and readmission within 30 days) in
cohort of 72 patients hospitalized for heart failure exacerbation (J Am Coll Cardiol 2001
Feb;37(2):386
see Natriuretic peptide and biomarkers testing for heart failure for further details
positive cardiac troponin test associated with in-hospital mortality in patients with acute
67,924 patients from ADHERE registry from 2001 to 2004 with acute decompensated heart
failure and serum creatinine level < 2 mg/dL (177 mcmol/L) had troponin level measured at time
of hospitalization
positive troponin test defined as cardiac troponin I level ≥ 1 mcg/L or cardiac troponin T level ≥
0.1 mcg/L
positive troponin test in 4,240 (6.2%) patients
in-hospital mortality 8% in patients with positive troponin test vs. 2.7% in patients with negative
troponin test (p < 0.001)
Reference - N Engl J Med 2008 May 15;358(20):2117 full-text
decreased relative lymphocyte count during hospitalization for heart failure associated with
increased risk of mortality or rehospitalization for heart failure within 100 days of discharge
based on cohort analysis of data from randomized trial
3,717 patients from EVEREST trial who were hospitalized for worsening heart failure with
ejection fraction ≤ 40% and complete blood counts within 48 hours of admission were evaluated
972 deaths and 1,515 cardiovascular deaths or heart failure hospitalizations occurred during
median 9.9 months follow-up
relative lymphocyte count = total number of lymphocytes ÷ total number of leukocytes × 100%
mean relative lymphocyte count 21.7% in overall analysis
24.9% had low relative lymphocyte count (< 15.4%)
within 100 days of discharge, decreased relative lymphocyte count during hospitalization
associated with increased risk of
all-cause mortality (adjusted hazard ratio 1.31, 95% CI 1.14-1.15 per 10% decrease)
cardiovascular mortality or heart failure hospitalization (adjusted hazard ratio 1.14, 95%
CI 1.04-1.25 per 10% decrease)
Reference - Circ Heart Fail 2012 Nov;5(6):750 full-text
in hospitalized heart failure patients with ejection fraction ≤ 40%, anemia at discharge but not
at admission may increase risk of death and short-term rehospitalization for heart failure
3,731 adults from EVEREST trial hospitalized for worsening heart failure with ejection fraction
≤ 40% were assessed for anemia at admission and/or discharge or day 7
anemia defined as hemoglobin < 12 g/dL for women and < 13 g/dL for men
34% had anemia at admission and 26% had anemia at discharge
compared to no anemia
anemia at discharge associated with increased risk of
all-cause mortality (adjusted hazard ratio 1.3, 95% CI 1.05-1.6)

short-term (≤ 100 days) cardiovascular mortality or rehospitalization for heart failure
(adjusted hazard ratio 1.73, 95% CI 1.37-2.18)
no significant differences in all-cause mortality or short-term cardiovascular mortality or
rehospitalization for heart failure with anemia at admission
no significant difference in long-term (> 100 days) cardiovascular mortality or
rehospitalization for heart failure with any anemia
Reference - Circ Heart Fail 2014 May;7(3):401
higher serum uric acid levels may be associated with increased mortality in patients
hospitalized for heart failure with reduced ejection fraction who have estimated glomerular
filtration rate ≥ 30 mL/minute/1.73 m2
3,955 adults from EVEREST trial hospitalized for worsening heart failure with ejection
fraction ≤ 40% were assessed for baseline serum uric acid levels
mean serum uric acid level 9.1 mg/dL
during median 9.9-month follow-up
all-cause mortality 26.3%
cardiovascular mortality or heart failure hospitalization in 40.7%
in analysis of 3,533 patients with baseline estimated glomerular filtration rate ≥ 30
mL/minute/1.73 m2, each 5 mg/dL increase in serum uric acid associated with increased
risk of
all-cause mortality (adjusted hazard ratio 1.44, 95% CI 1.22-1.69)
cardiovascular mortality or heart failure hospitalization (adjusted hazard ratio 1.44,
95% CI 1.26-1.64)
no significant association between serum uric acid levels and mortality in patients with
baseline estimated glomerular filtration rate < 30 mL/minute/1.73 m2
Reference - Am J Cardiol 2014 Dec 1;114(11):1713
in patients with heart failure, persistently elevated jugular venous pressure and third heart
sound are each associated with increased risk for heart failure hospitalization or death
2,569 patients with presence or history of symptomatic heart failure randomized to enalapril vs.
placebo
in retrospective analysis of physical exam findings at study entry, elevated jugular venous
pressure and third heart sound were each associated with increased risks for
hospitalization for heart failure
death or hospitalization for heart failure
death from pump failure
Reference - N Engl J Med 2001 Aug 23;345(8):574
elevated admission blood glucose levels associated with increased mortality in hospital and at 60
days, but not at 6 months or 1 year
1,122 patients without diabetes admitted with acute heart failure or acute exacerbation of chronic
heart failure evaluated
each 18 mg/dL (1 mmol/L) increase in admission glucose level associated with increased risk for
in-hospital mortality (adjusted odds ratio 1.31, 95% CI 1.1-1.57)
60-day mortality (adjusted hazard ratio 1.12, 95% CI 1.01-1.25)

Reference - Arch Intern Med 2006 Aug 14-28;166(15):1613, commentary can be found in Am
Fam Physician 2006 Dec 1;74(11):1960
persistent hyponatremia associated with increased 6-month mortality and rehospitalization rate
433 hospitalized adult patients with heart failure evaluated
hyponatremia defined as serum sodium ≤ 134 mEq/L
hyponatremia present in 23.8% of patients and persistent hyponatremia (present throughout
hospital course) in 16.4% of patients
compared to normonatremic patients, patients with persistent hyponatremia had increased risk of
all-cause mortality at 6 months (adjusted hazard ratio [HR] 1.82, 95% CI 1.03-3.22)
heart failure rehospitalization (adjusted HR 1.52, 95% CI 1.05-2.22)
Reference - Arch Intern Med 2007 Oct 8;167(18):1998
Readmission risk
The Centers for Medicare and Medicaid Services (CMS) financially penalizes hospitals for
readmissions and hospitalizations believed to be avoidable(6)
clinical risk scores reportedly do not perform well to estimate risk of hospital readmission(6)
to help avoid unnecessary readmissions for heart failure, the following are recommended for all heart
failure patients(6)
medication reconciliation
careful transitions between care settings
improved communication between clinicians and nurses
consistent documentation are encouraged for all heart failure patients
1-year readmission rate 67.4% following hospitalization for heart failure in older patients (level
2 [mid-level] evidence)
patients ≥ 65 years old on Medicare who survived hospitalization for heart failure, acute
myocardial infarction, or pneumonia were followed for up to 1 year
972,339 patients had 1,462,453 hospitalizations for heart failure
1-year readmission rate 67.4%
compared to general Medicare population, patients with heart failure had increased risk of
readmission
at 30 days (adjusted standardized incidence ratio 15.8, 95% CI 15.7-15.9)
at 1 year (adjusted standardized incidence ratio 3.5, 95% CI 3.5-3.5)
Reference - BMJ 2015 Feb 5;350:h411 full-text
statistical models for predicting patient readmission risk after heart failure are inconsistent
based on systematic review of studies limited by heterogeneity
systematic review of 117 studies of risk factors or prediction models for readmission after heart
failure hospitalization in adults
0 studies had models comparing hospital readmission rates
5 (4.3%) studies had models to predict patients' risk of readmission
112 (95.7%) studies evaluated patient characteristics associated with readmission
studies had significant heterogeneity including multiple data sources, varied definitions for case
identification, outcomes, and time periods

few patient characteristics consistently associated with readmission
2 studies reported modest model discrimination of readmission risk in patients
Reference - Arch Intern Med 2008 Jul 14;168(13):1371
diuretic response and hemoconcentration after hospitalization for acute heart failure may have
modest discrimination between low and high risk for hospital readmission (level 2 [mid-level]
evidence)
based on posthoc analysis of 2 randomized trials serving as independent derivation (PROTECT)
and validation (EVEREST) cohorts
derivation cohort included 1,180 patients (mean age 70 years, 68% male) with mild-moderate
renal dysfunction and acute heart failure
validation cohort included 1,776 patients (mean age 65 years, 74% male) with reduced ejection
fraction hospitalized for worsening heart failure
diuretic response defined as weight change per 40 mg of furosemide or equivalent on day 4 after
admission
poor response is above median
good response is below median
hemoconcentration defined as an increase in hemoglobin at discharge or day 7 after admission,
whichever came first
poor response is below median
good response is above median
readmission rate in 21.1% of derivation cohort and 11.8% in validation cohort
60-day readmission rate by response category in derivation and validation cohorts
Response Category Derivation Cohort Validation Cohort
good diuretic response
11% for 321 patients 9% for 480 patients
good hemoconcentration
good diuretic response
poor hemoconcentration
poor diuretic response
good hemoconcentration
poor diuretic response
poor hemoconcentration
patients in validation cohort had lower prevalence of comorbidities than derivation cohort
Reference - Circ Heart Fail 2016 Jun;9(6):e002845
Prevention and Screening

Prevention
heart failure prevention refers to detection and management of asymptomatic patients at risk for
developing heart failure before first clinical episode of heart failure occurs
risk scores derived from clinical risk factors that identify asymptomatic patients
ABC Heart Failure Risk Score has moderate discrimination in predicting 5-year risk of
developing heart failure in older adults (level 1 [likely reliable] evidence)
Framingham Heart Failure Risk Score has fair discrimination in predicting 10-year risk of
developing heart failure in patients aged 45-64 years (level 1 [likely reliable] evidence)
screening for underlying structural heart disease
natriuretic peptide testing
does not appear useful for general population screening
pro-brain natriuretic peptide (pro-BNP) may be useful for ruling out left ventricular
ejection fraction < 40% (level 2 [mid-level] evidence)
N-terminal pro-brain natriuretic peptide (NT-proBNP) may be useful for ruling out
ventricular dysfunction in patients with stable coronary artery disease and no history of
heart failure (level 2 [mid-level] evidence)
echocardiography
routine regular population screening for asymptomatic reduced left ventricular ejection
fraction (LVEF) is not recommended
imaging modality of choice that can distinguish Stage A and Stage B heart failure
echocardiographic evaluation indicated for patients at high risk for reduced LVEF who
have any
strong family history of cardiomyopathy
long-standing hypertension
previous myocardial infarction
cardiotoxic therapies
≥ 2 risk factors for developing heart failure (Stage A heart failure)
chronic right ventricular pacing to detect asymptomatic left ventricular dysfunction
echocardiographic screening for structural and valvular heart disease in the general
population not associated with decreased risk of death, myocardial infarction, or stroke
Guidelines on genetic screening strategies
screening recommended in first-degree relatives of patients with hypertrophic
cardiomyopathy (ACCF/AHA Class I, Level B)
ongoing screening is not indicated in genotype negative relatives in families with
hypertrophic cardiomyopathy (ACCF/AHA Class III, Level B)
management strategies for asymptotic heart failure include
early detection and risk-reduction strategies to delay progression or potentially reverse treatable
causes (Stage A)
treatment of structural heart disease (Stage B)
American College of Cardiology Foundation and American Heart Association (ACCF/AHA)
recommendations for prevention of symptomatic heart failure
in patients with Stage A heart failure
control hypertension (systolic and diastolic blood pressure) and lipid disorders
(ACCF/AHA Class I, Level A)
control or avoid other contributory factors such as obesity, diabetes, tobacco use, and
known cardiotoxic drugs (such as alcohol) (ACCF/AHA Class I, Level C)
in patients with Stage B heart failure
all recommendations and treatment for patients with Stage A heart failure generally apply
to patients with Stage B heart failure

in all patients with recent or remote history of ST-elevation myocardial infarction (STEMI)
or acute coronary syndrome and reduced ejection fraction(1)
use angiotensin-converting enzyme (ACE) inhibitors to prevent symptomatic heart
failure and reduce mortality; angiotensin receptor blockers (ARBs) are appropriate
unless contraindicated in patients intolerant of ACE inhibitors (ACCF/AHA Class I,
Level A)
use evidence-based beta blockers (such as carvedilol) to reduce mortality
(ACCF/AHA Class I, Level B)
use statins to prevent symptomatic heart failure and cardiovascular events
(ACCF/AHA Class I, Level A)
nondihydropyridine calcium channel blockers with negative inotropic effects may be
harmful in asymptomatic patients with low left ventricular ejection fraction and no
symptoms of heart failure after myocardial infarction (ACCF/AHA Class III Harm,
Level C)
in all patients with reduced ejection fraction, even without history of myocardial
infarction(1)
use ACE inhibitors to prevent symptomatic heart failure (ACCF/AHA Class I, Level
A)
use beta blockers to prevent symptomatic heart failure (ACCF/AHA Class I, Level
C)
European Society of Cardiology recommendations for prevention of symptomatic heart failure
in patients without structural heart disease (Stage A heart failure)
treatment of hypertension recommended to prevent or delay onset of heart failure and
prolong life (ESC Class I, Level A)
treatment with statins recommended in patients with or at high-risk of coronary artery
disease, whether or not they have left ventricular systolic dysfunction, to prevent or delay
onset of heart failure and prolong life (ESC Class I, Level A)
counseling and treatment for smoking cessation and alcohol intake reduction
recommended in patients who smoke or consume excess alcohol to prevent or delay onset
of heart failure (ESC Class I, Level C)
treatment of other risk factors of heart failure (including obesity and dysglycemia)
suggested to prevent or delay onset of heart failure (ESC Class IIa, Level C)
empagliflozin suggested in patients with type 2 diabetes should be considered to prevent or
delay onset of heart failure and prolong life (ESC Class IIa, Level B)
ACE inhibitors suggested in patients with stable coronary artery disease, even if they do
not have left ventricular systolic dysfunction, to prevent or delay onset of heart failure
(ESC Class IIa, Level A)
in patients with asymptomatic structural heart disease (Stage B heart failure)
all recommendations and treatment for patients with Stage A heart failure generally apply
to patients with Stage B heart failure
ACE inhibitors recommended in patients with
asymptomatic left ventricular systolic dysfunction and history of myocardial
infarction to prevent or delay onset of heart failure and prolong life (ESC Class I,
Level A)
asymptomatic left ventricular systolic dysfunction without history of myocardial
infarction to prevent or delay onset of heart failure (ESC Class I, Level B)
beta-blocker recommended in patients with asymptomatic left ventricular systolic

dysfunction and history of myocardial infarction to prevent or delay onset of heart failure
or prolong life (ESC Class I, Level B)
implantable cardioverter defibrillator recommended to prevent sudden death and prolong
life in patients with (ESC Class I, Level B)
asymptomatic left ventricular systolic dysfunction (left ventricular ejection fraction
≤ 30%) of ischemic origin, who are ≥ 40 days after acute myocardial infarction
asymptomatic non-ischemic dilated cardiomyopathy (left ventricular ejection
fraction ≤ 30%) who receive optimal medical therapy
strategies for prevention of heart failure include
lifestyle modification
advise patients to
cease smoking and remain abstinent
modify lifestyle
lose weight
exercise regularly
dietary measures associated with lower incidence of heart failure
greater fish consumption, but not fried fish (level 2 [mid-level] evidence)
whole grain breakfast cereals (level 2 [mid-level] evidence)
moderate alcohol consumption (definitions vary across studies but generally
approximately 1-4 drinks/day) (level 2 [mid-level] evidence)
vaccinations
influenza vaccination of older persons associated with reduced hospitalization for
heart failure (level 2 [mid-level] evidence)
pneummococcal vaccination may be indicated for adults ≥ 65 years old, and adults
aged 19-64 years with specific indications
medications that may reduce incidence of heart failure in patients with Stage A heart failure include
antihypertensive medications
angiotensin-converting enzyme (ACE) inhibitors
angiotensin receptor blockers (ARBs)
beta blockers
diuretics
statins
calcium channel blockers may not be as effective as other antihypertensive medications in preventing
heart failure in patients with hypertension (level 2 [mid-level] evidence)
medications that appear to reduce left ventricular hypertrophy in patients with Stage B heart failure
include (level 3 [lacking direct] evidence)
ramipril
telmisartan
high-dose metoprolol
see Heart failure screening and prevention for details

dobutamine use with postoperative hemodynamic optimization may reduce risk of postoperative
pulmonary edema in high-risk patients (level 2 [mid-level] evidence)
50 elderly patients with coexisting pathologies having major elective surgery had pulmonary
artery catheter-guided hemodynamic optimization during operation and 24 hours postoperatively

to achieve supranormal oxygen delivery index > 600 mL/minute/m2
hemodynamic optimization randomized to fluids and dobutamine vs. fluids alone
comparing fluids and dobutamine vs. fluids alone
cardiovascular complications in 4 patients (16%) vs. 13 patients (52%) (p < 0.05, NNT 3),
primarily due to 3 (12%) vs. 10 (40%) patients having acute heart failure or pulmonary
edema (NNT 4)
28-day mortality 8% vs. 20% (not significant)
60-day mortality 8% vs. 28% (not significant)
Reference - Crit Care 2006;10(3):R72 full-text
Quality Improvement
Medicare/Joint Commission National Hospital Inpatient Quality Measures
Emergency Department (ED) measures

ED-1 Median Time from ED Arrival to ED Departure for Admitted ED Patients
ED-1a - overall rate
ED-1b - reporting measure
ED-1c - psychiatric/mental health patients
measured as time (in minutes) from emergency department (ED) arrival to ED departure
for patients admitted to facility from ED
ED-2 Admit Decision Time to ED Departure Time for Admitted Patients
ED-2a - overall rate
ED-2b - reporting measure
ED-2c - psychiatric/mental health patients
measured as time (in minutes) from admit decision time to time of departure from
emergency department (ED) for ED patients admitted to inpatient status
see Medicare/Joint Commission National Hospital Inpatient Quality Measures for additional
information
Physician Quality Reporting System Quality Measures
5. Heart Failure: Angiotensin-Converting Enzyme (ACE) Inhibitor or Angiotensin Receptor Blocker

(ARB) Therapy for Left Ventricular Systolic Dysfunction (LVSD)
Percentage of patients ≥ 18 years old with a diagnosis of heart failure with a current or prior left
ventricular ejection fraction (LVEF) < 40% who were prescribed ACE inhibitor or ARB therapy
either within a 12-month period when seen in the outpatient setting or at each hospital discharge
American College of Physicians (ACP) supports this measure (ACP Performance Measure
Review 2014 Jul 26 PDF)
8. Heart Failure: Beta blocker Therapy for Left Ventricular Systolic Dysfunction
Percentage of patients ≥ 18 years old with a diagnosis of heart failure with a current or prior left
ventricular ejection fraction (LVEF) < 40% who were prescribed beta blocker therapy either
within a 12-month period when seen in the outpatient setting or at each hospital discharge
American College of Physicians (ACP) supports this measure (ACP Performance Measure
Review 2014 Jul 26 PDF)
see Physician Quality Reporting System Quality Measures for additional information
Quality and Outcomes Framework Indicators

HF1. Contractor establishes and maintains a register of patients with heart failure
HF2. Percentage of patients with diagnosis of heart failure diagnosed on or after 1 April 2006 which
have been confirmed by echocardiogram or specialist assessment 3 months before or 12 months after
entering on to the register
HF3. Percentage of patients with current diagnosis of heart failure due to left ventricular systolic
dysfunction who are currently treated with angiotensin-converting enzyme (ACE) inhibitor or
angiotensin receptor blocker (ARB)
HF4. Percentage of patients with current diagnosis of heart failure due to left ventricular systolic
dysfunction and currently treated with angiotensin-converting enzyme (ACE) inhibitor or angiotensin
receptor blocker (ARB) who are additionally currently treated with beta blocker licensed for heart
failure
see Quality and Outcomes Framework Indicators for additional information
Quality improvement evidence

heart failure performance measures not generally associated with mortality or rehospitalization
within 60-90 days
5,791 patients hospitalized with heart failure at 91 hospitals in United States 2003-2004
evaluated
American College of Cardiology and American Heart Association (ACC/AHA) performance
measures are
discharge instructions or educational materials addressing activity level, diet, discharge
medications, follow-up appointment, weight monitoring, and what to do if symptoms
worsen
evaluation of left ventricular systolic function
angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB)
prescription if left ventricular systolic dysfunction and no contraindications
smoking cessation advice or counseling during hospital stay, if history of smoking
warfarin prescription if chronic or recurrent atrial fibrillation and no contraindications
attainment of performance measures (among eligible patients) in 5,791 patients in follow-up
cohort vs. 48,612 patients in overall registry
66% vs. 54% received discharge instructions
89% vs. 87% had evaluation of left ventricular systolic function
83% vs. 83% had ACE inhibitor or angiotensin receptor blocker
72% vs. 62% had smoking cessation counseling
53% vs. 52% had warfarin for atrial fibrillation

84% vs. 83% had beta blocker at discharge (not a current performance measure)
at 60-90 days, 8.6% mortality and 36.2% mortality or rehospitalization
only performance measures which retained significant associations with mortality, and mortality
or rehospitalization, after adjustment for risk were
ACE inhibitor or angiotensin receptor blocker for left ventricular dysfunction
beta blocker at discharge
Reference - JAMA 2007 Jan 3;297(1):61, commentary can be found in JAMA 2007 Apr
11;297(14):1547
Guidelines and Resources

Guidelines
International guidelines
National Academy of Clinical Biochemistry/International Federation of Clinical Chemistry and

Laboratory Medicine (NACB/IFCC) Committee for standardization of markers of cardiac damage
laboratory medicine practice guidelines on
analytical issues for biomarkers of heart failure can be found in Clin Biochem 2008 Mar;41(4-
5):222, Circulation 2007 Jul 31;116(5):e95 full-text
clinical utilization of cardiac biomarker testing in heart failure can be found in Clin Biochem
2008 Mar;41(4-5):210, Circulation 2007 Jul 31;116(5):e99 full-text
United States guidelines
American College of Cardiology Foundation/American Heart Association (ACCF/AHA) 2013

guideline on management of heart failure
American College of Cardiology/American Heart Association/Heart Failure Society of America
(ACC/AHA/HFSA) focused update of the 2013 ACCF/AHA guideline on the management of
heart failure can be found in J Card Fail 2017 Aug;23(8):628 full-text
ACC/AHA/HFSA focused update on new pharmacological therapy can be found in Circulation
2016 Sep 27;134(13):e282 or in J Am Coll Cardiol 2016 Sep 27;68(13):1476
original guideline can be found in J Am Coll Cardiol 2013 Oct 15;62(16):e147 full-text or in
Circulation 2013 Oct 15;128(16):e240 full-text, executive summary can be found in Circulation
2013 Oct 15;128(16):1810
American College of Emergency Physicians (ACEP) clinical policy on evaluation and management of
adult patients presenting to emergency department with acute heart failure syndromes can be found in
Ann Emerg Med 2007 May;49(5):627 full-text
Heart Failure Society of America (HFSA) 2010 practice guideline on comprehensive heart failure can
be found in J Card Fail 2010 Jun;16(6):e1, commentary can be found in J Card Fail 2011 Jan;17(1):1
HFSA 2010 guideline section on

evaluation and management of patients with acute decompensated heart failure can be found in J
Card Fail 2010 Jun;16(6):e134 or at National Guideline Clearinghouse 2010 Dec 20:23908
Institute for Clinical Systems Improvement (ICSI) guideline on heart failure in adults can be found at
National Guideline Clearinghouse 2010 Aug 30:15528
Academy of Nutrition and Dietetics (AND) evidence-based nutrition practice guideline on heart failure
can be found at AND
American Society of Echocardiography/American College of Emergency Physicians (ASE/ACEP)

consensus statement on focused cardiac ultrasound in emergent setting can be found in J Am Soc
Echocardiogr 2010 Dec;23(12):1225
American College of Cardiology/American Heart Association/American Society of Echocardiography

(ACC/AHA/ASE) guideline on clinical application of echocardiography can be found in J Am Coll
Cardiol 2003 Sep 3;42(5):954 full-text, J Am Soc Echocardiogr 2003 Oct;16(10):1091, or in
Circulation 2003 Sep 2;108(9):1146 full-text
American College of Chest Physicians (ACCP) Evidence-Based Clinical Practice Guidelines on

Antithrombotic Therapy and Prevention of Thrombosis (Ninth Edition) recommendations on
prevention of venous thromboembolism in nonsurgical patients can be found in Chest 2012 Feb;141(2
Suppl):e195S full-text, commentary can be found in Chest 2012 Jul;142(1):265 full-text
American College of Physicians (ACP) clinical practice guideline on venous thromboembolism

prophylaxis in hospitalized patients can be found in Ann Intern Med 2011 Nov 1;155(9):625, editorial
can be found in Ann Intern Med 2011 Nov 1;155(9):638
United Kingdom guidelines
National Institute for Health and Care Excellence (NICE) guideline on diagnosing and managing acute
heart failure in adults can be found at NICE 2014 Oct:CG187 PDF or at National Guideline
Clearinghouse 2015 Mar 9:48752, summary can be found in BMJ 2014 Oct 8;349:g5695
National Institute for Health and Care Excellence (NICE) guidance on ivabradine for treatment of
chronic heart failure can be found at NICE 2012 Nov:TA267 PDF or at National Guideline
Clearinghouse 2013 Mar 11:39220
Canadian guidelines
Canadian Cardiovascular Society (CCS) heart failure companion can be found in Can J Cardiol 2016
Mar;32(3):296 PDF
Canadian Cardiovascular Society (CCS) consensus conference recommendations on heart failure
2012 update (focus on acute and chronic heart failure) can be found in Can J Cardiol 2013
Feb;29(2):168
2011 update (focus on sleep apnea, renal dysfunction, mechanical circulatory support, and
palliative care) can be found in Can J Cardiol 2011 May-Jun;27(3):319, commentary can be
found in Can J Cardiol 2011 Nov;27(6):871
2010 update (heart failure in ethnic minority populations, heart failure and pregnancy, disease
management, and quality improvement/assurance programs) can be found in Can J Cardiol 2010
Apr;26(4):185 full-text
2009 update (diagnosis and management of right-sided heart failure, myocarditis, device therapy,
and recent important clinical trials) can be found in Can J Cardiol 2009 Feb;25(2):85 full-text
2008 update (best practices on transition of care of heart failure patients, and recognition,
investigation, and treatment of cardiomyopathies) can be found in Can J Cardiol 2008
Jan;24(1):21 full-text
2007 update (prevention, management during intercurrent illness or acute decompensation, and
use of biomarkers) can be found in Can J Cardiol 2007 Jan;23(1):21 full-text
CCS consensus conference recommendations on heart failure 2006 (diagnosis and management)
can be found at Can J Cardiol 2006 Jan;22(1):23 full-text, correction can be found in Can J
Cardiol 2006 Mar 1;22(3):271
European guidelines
European Society of Cardiology (ESC) guideline on diagnosis and treatment of acute and chronic heart
failure can be found in Eur Heart J 2016 Jul 14;37(27):2129
ESC scientific statement on assessing and grading congestion in acute heart failure can be found in Eur
J Heart Fail 2010 May;12(5):423 full-text, commentary can be found in Eur J Heart Fail 2010
Oct;12(10):1140
Spanish Society of Intensive Care Medicine and Coronary Units (SEMICYUC) clinical practice
guideline on management of low cardiac output syndrome in postoperative period of heart surgery can
be found in Med Intensiva 2012 May;36(4):e1, summary can be found in Med Intensiva 2012
May;36(4):277 [Spanish]
Central and South American guidelines
Sociedade Brasileira de Cardiologia (SBC)

SBC Brazilian guidelines on acute cardiac insufficiency can be found in Arq Bras Cardiol
2009;93(3 Suppl 3):2 full-text [Portuguese]
summary of SBC Brazilian guideline update on acute heart failure can be found in Arq Bras
Cardiol 2012 May;98(5):375 full-text [English, Portuguese]
Review articles
review of acute compensated heart failure can be found in Circ J 2012;76(3):532

review of treatment for acute compensated heart failure can be found in Cardiol Clin 2014
Feb;32(1):145
review of heart failure can be found in Lancet 2009 Mar 14;373(9667):941
review of diagnosis and management of heart failure can be found in Mayo Clin Proc 2014
May;89(5):662
review of diagnosis and evaluation of heart failure can be found in Am Fam Physician 2012 Jun
15;85(12):1161
review of evaluation of patients with heart failure can be found in Cardiol Clin 2014 Feb;32(1):47
review of initial management of acute heart failure can be found in Heart Fail Clin 2013 Jul;9(3):291
review of heart failure pathophysiology can be found in Cardiol Clin 2014 Feb;32(1):9
review of early management of acute decompensated heart failure can be found in Can J Cardiol 2008
Jul;24 Suppl B:9B full-text
review of heart failure as a complication of acute myocardial infarction can be found in Clin Geriatr
Med 2007 Feb;23(1):123
review of acute pulmonary edema can be found in N Engl J Med 2005 Dec 29;353(26):2788
review of pulmonary artery wedge pressure can be found in Am Fam Physician 1996 Sep 1;54(3):1039
review of biomarkers in heart failure can be found in N Engl J Med 2008 May 15;358(20):2148
review of biomarkers and therapies for patients with acute heart failure and renal dysfunction can be
found in Am J Med 2015 Mar;128(3):312.e1
review of nutrition and heart failure can be found in Nutr Clin Pract 2009 Feb-Mar;24(1):60
review of high output heart failure can be found in QJM 2009 Apr;102(4):235 full-text
review of end-of-life conversations with heart failure patients can be found in Br J Gen Pract 2011
Jan;61(582):e49
case presentation of high-output heart failure can be found in N Engl J Med 2012 Dec 6;367(23):2241
case series of 57 children presenting to emergency department with acute heart failure (including
clinical findings, management and outcomes) can be found in Pediatrics 2009 Nov;124(5):e898
case presentation of swimming-induced pulmonary edema can be found in Am Fam Physician 2004
Mar 1;69(5):1046
MEDLINE search
to search MEDLINE for (Acute heart failure) with targeted search (Clinical Queries), click therapy,
diagnosis, or prognosis
Patient Information
information on heart failure from National Heart, Lung, and Blood Institute
handout on heart failure from Sociedad Española de Medicina de Familia y Comunitaria PDF [Spanish]
handout on heart failure from Patient UK PDF
handout on heart failure from Mayo Clinic
handout on heart attack from American Academy of Family Physicians or in Spanish
handout on living well with heart failure from Irish Heart Foundation PDF
ICD-9/ICD-10 Codes
ICD-9 codes
428 heart failure

428.0 congestive heart failure, unspecified
428.1 left heart failure
428.2 systolic heart failure
428.21 systolic heart failure, acute
428.23 systolic heart failure, acute on chronic
428.3 diastolic heart failure

428.21 diastolic heart failure, acute
428.23 diastolic heart failure, acute on chronic
428.3 combined systolic and diastolic heart failure
428.21 combined systolic and diastolic heart failure, acute
428.23 combined systolic and diastolic heart failure, acute on chronic
428.9 heart failure, unspecified
429.4 functional disturbances following cardiac surgery
518.4 acute pulmonary edema
see Heart failure with reduced ejection fraction for additional ICD-9 codes
ICD-10 codes
I50 heart failure
I50.0 congestive heart failure
I50.1 left ventricular failure
I50.9 heart failure, unspecified
I97.1 other functional disturbances following cardiac surgery
J68.1 acute pulmonary edema due to chemicals, gases, fumes and vapors
J81 pulmonary edema
ICD-10-CM codes for United States

I50 heart failure
I50.1 left ventricular failure
I50.2 systolic (congestive) heart failure
I50.20 unspecified systolic (congestive) heart failure
I50.21 acute systolic (congestive) heart failure
I50.22 chronic systolic (congestive) heart failure
I50.23 acute on chronic systolic (congestive) heart failure
I50.3 diastolic (congestive) heart failure
I50.30 unspecified diastolic (congestive) heart failure
I50.31 acute diastolic (congestive) heart failure
I50.32 chronic diastolic (congestive) heart failure
I50.33 acute on chronic diastolic (congestive) heart failure
I50.4 combined systolic (congestive) and diastolic (congestive) heart failure
I50.40 unspecified combined systolic (congestive) and diastolic (congestive) heart
failure
I50.41 acute combined systolic (congestive) and diastolic (congestive) heart failure
I50.42 chronic combined systolic (congestive) and diastolic (congestive) heart
failure
I50.43 acute on chronic combined systolic (congestive) and diastolic (congestive)
heart failure
I50.9 heart failure, unspecified
References
General references used
1. Allen LA, O'Connor CM. Management of acute decompensated heart failure. CMAJ. 2007 Mar
13;176(6):797-805 full-text, commentary can be found in CMAJ 2007 Jul 17;177(2):175 full-text
2. Bayram M, De Luca L, Massie MB, Gheorghiade M. Reassessment of dobutamine, dopamine, and
milrinone in the management of acute heart failure syndromes. Am J Cardiol. 2005 Sep
19;96(6A):47G-58G
3. Wang CS, FitzGerald JM, Schulzer M, Mak E, Ayas NT. Does this dyspneic patient in the
emergency department have congestive heart failure? JAMA. 2005 Oct 19;294(15):1944-56
4. Badgett RG, Lucey CR, Mulrow CD. Can the clinical examination diagnose left-sided heart failure
in adults? JAMA. 1997 Jun 4;277(21):1712-9
5. Lindenfeld J, Albert NM, Boehmer JP, et al; Heart Failure Society of America. HFSA 2010
Comprehensive Heart Failure Practice Guideline. J Card Fail. 2010 Jun;16(6):e1-194 or at National
Guideline Clearinghouse 2010 Dec 20:23908, commentary can be found in J Card Fail 2011
Jan;17(1):1
6. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart
failure: a report of the American College of Cardiology Foundation/American Heart Association Task
Force on practice guidelines. Circulation. 2013 Oct 15;128(16):e240 PDF, also published in J Am Coll
Cardiol 2013 Oct 15;62(16):e147
7. Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, Falk V, González-Juanatey
JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley
JP, Rosano GM, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P, Authors/Task Force Members.
2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task
Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of
Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of
the ESC. Eur Heart J. 2016 Jul 14;37(27):2129-200 full-text
Recommendation grading systems used

American College of Cardiology Foundation/American Heart Association (ACCF/AHA) grading
system for recommendations
classifications of recommendations
Class I - procedure or treatment should be performed or administered
Class IIa - reasonable to perform procedure or administer treatment, but additional studies
with focused objectives needed
Class IIb - procedure or treatment may be considered; additional studies with broad
objectives needed, additional registry data would be useful
Class III - procedure or treatment should not be performed or administered because it is
not helpful or may be harmful
Class III ratings may be subclassified as Class III No Benefit or Class III Harm
levels of evidence
Level A - data derived from multiple randomized clinical trials or meta-analyses
Level B - data derived from single randomized trial or nonrandomized studies
Level C - only consensus opinions of experts, case studies, or standard of care
Reference - ACCF/AHA 2013 guideline on management of heart failure (Circulation 2013 Oct
15;128(16):e240 PDF)
American College of Chest Physicians (ACCP) grades

Grade 1 - strong recommendation based on clear risk/benefit balance
Grade 2 - weak recommendation based on unclear or close risk/benefit balance
Grade A - high-quality evidence based on consistent evidence from randomized trials without
important limitations or exceptionally strong evidence from observational studies
Grade B - moderate-quality evidence based on randomized trials with important limitations
(inconsistent results, methodologic flaws, indirect or imprecise results) or very strong evidence
from observational studies
Grade C - low- or very low-quality evidence based on observational studies, case series, or
randomized trials with serious flaws or indirect evidence
Reference - ACCP evidence-based clinical practice guideline on methodology for development
of antithrombotic therapy and prevention of thrombosis (Chest 2012 Feb;141(2 Suppl):53S full-
text), commentary can be found in Chest 2013 Apr;143(4):1190
American College of Physicians (ACP) guideline grading system

strength of recommendation
Strong - benefits clearly outweigh risks and burden, or risks and burden clearly outweigh
benefits
Weak - benefits finely balanced with risks and burden
Insufficient - balance of benefits and risks cannot be determined
quality of evidence
High - randomized trials without important limitations, or overwhelming evidence from
observational studies
Moderate - randomized trials with important limitations (inconsistent results,
methodologic flaws, indirect, or imprecise), or exceptionally strong evidence from
observational studies
Low - observational studies or case series
Insufficient - evidence is conflicting, poor quality, or lacking
Reference - ACP methods for development of clinical practice guidelines and guidance
statements (Ann Intern Med 2010 Aug 3;153(3):194)
British Thoracic Society grades of recommendation

Grade A - based on evidence from high quality meta-analyses, systematic reviews, or
randomized trials directly applicable to target population or on body of evidence including well-
conducted meta-analyses, systematic reviews, or randomized trials with low risk of bias
Grade B - based on body of evidence including high quality systematic reviews of case-control
or cohort studies directly applicable to target population with consistent results or on evidence
extrapolated from high quality meta-analyses, systematic reviews, or randomized trials
Grade C - based on evidence from well-conducted case-control or cohort studies directly
applicable to target population or on evidence extrapolated from high quality systematic reviews
of case-control or cohort studies
Grade D - based on evidence from case reports, case series, expert opinion or extrapolated from
well-conducted case-control or cohort studies
Reference - BTS guideline on noninvasive ventilation in acute respiratory failure (Thorax 2002
Mar;57(3):192 PDF)
European Society of Cardiology (ESC) grading system for recommendations
classes of recommendations
Class I - evidence and/or general agreement that given treatment or procedure is beneficial,
useful, and effective
Class II - conflicting evidence and/or divergence of opinion about usefulness/efficacy of
given treatment or procedure
Class IIa - weight of evidence/opinion in favor of usefulness/efficacy
Class IIb - usefulness/efficacy less well established by evidence/opinion
Class III - evidence or general agreement that given treatment or procedure is not
useful/effective, and in some cases may be harmful
levels of evidence
Level A - data derived from multiple randomized clinical trials or meta-analyses
Level B - data derived from single randomized trial or large nonrandomized studies
Level C - consensus of opinion of experts and/or small studies, retrospective studies,
registries
Reference - ESC guideline on diagnosis and treatment of acute and chronic heart failure (Eur
Heart J 2016 Jul 14;37(27):2129)
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DynaMed Plus: Acute heart failure 2017-12-20, 10(11 PM

Acute heart failure

when transthoracic echocardiography is inadequate (Weak recommendation).

acute decompensated heart failure

American College of Cardiology Foundation/American Heart Association (ACCF/AHA) staging of

ACCF/AHA Staging of Heart Failure:

Reference - Circulation 2013 Oct 15;128(16):e240 PDF

New York Heart Association (NYHA) functional classification

NYHA Functional Classification:

Reference - Circulation 2013 Oct 15;128(16):e240 PDF

Who is most affected

Likely risk factors

Possible risk factors

nonsteroidal anti-inflammatory drugs (NSAIDs)

randomly selected non-NSAID users were evaluated

glitazones associated with heart failure

medications which may worsen heart failure include

fine particulate air pollution associated with hospital admission rate

Etiology and Pathogenesis

left ventricular dysfunction(1)

History and Physical

Chief concern (CC)

common signs and symptoms include(1, 3)

fatigue and weight gain

History of present illness (HPI)

Past medical history (PMH)

ask about conditions that may be causes or risk factors, including(3, 6)

Family history (FH)

ask about family history of(6)

Social history (SH)

ask about potential causes or risk factors, including

Blood pressure and pulse response to Valsalva maneuver

blood pressure response to Valsalva maneuver

jugular venous distention(3, 4, 5, 6)

normal apical impulse is located in fourth or fifth intercostal space(4)

third heart sound (S3, ventricular filling gallop)(1, 3, 6)

prospective study of 90 adults undergoing nonemergent left heart catheterization

fourth heart sound (S4, atrial gallop)(3)

edema (may also occur proximally in dependent areas of bed-bound patients)(1, 3)

Male genital exam

tests that may help confirm diagnosis include(1)

Recommendations for blood tests

American College of Cardiology Foundation/American Heart Association (ACCF/AHA)

Brain natriuretic peptide (BNP) testing

in patients presenting with acute dyspnea

Cardiac troponin and other biomarker testing

pulmonary congestion (ESC Class I, Level C)

summary can be found in Am Fam Physician 2004 Nov 15;80(10):2004

2-dimensional echocardiography with Doppler should be performed during initial evaluation of

ventricular wall motion

echocardiography (EDecho) performed by emergency department physicians

American College of Cardiology/American Heart Association/American Society of Echocardiography

specificity 83% vs. 44% (p < 0.05)

> 50% (normal) in 42 patients (49%)

Noninvasive imaging for myocardial ischemia and viability

Magnetic resonance imaging

American College of Radiology (ACR) Appropriateness Criteria

Other diagnostic testing

General treatment of acute heart failure

Treatment considerations after initial stabilization of acute heart failure

thromboembolism prophylaxis with unfractionated heparin, low-molecular-weight heparin, or

hospital-at-home care reported to be feasible in prospective study of 455 community-dwelling elderly

if perfusion inadequate (also referred to as wet and cold patient)