Terms have been used to characterize AHF in the
“acute heart failure syndromes” (AHFSs),
“acute(ly) decompensated heart failure” (ADHF),
“acute decompensation of chronic heart failure”
“hospitalization for heart failure” (HHF).
Acute Heart failure Definition:
AHF can be defined as:
“ The new onset or recurrence of symptoms and
signs of heart failure requiring urgent or
emergent therapy and resulting in seeking
unscheduled care or hospitalization.”
Although the designation “acute” in the nomenclature
suggests a sudden onset of symptoms, many patients
may have a more subacute course, with gradual
worsening of symptoms that ultimately reach a level of
severity sufficient to seek unscheduled medical care.
Scope of the Problem
The overall number of hospitalizations for
heart failure continues to grow as a
Aging of the population,
Improved survival after acute MI,
Effective prevention of SCD.
Preserved vs Reduced Ejection Fraction
Unexpectedly high prevalence of HFpEF in AHF
HFpEF are more likely to be older, to be female, and to have
a history of hypertension, less likely underlying CAD
The in-hospital mortality for patients with HFpEF appears
to be lower than that for patients with depressed LV
ejection fraction (LVEF), but postdischarge
rehospitalization rates are similarly high for both
Comorbid Conditions with AHF
represent diseases that are risk factors for the development
of heart failure and also can complicate diagnosis and
Hypertension is the most prevalent 60%
Dyslipidemia > 30%
Other conditions that are the result of the vascular injury
produced by these diseases, such as Stroke, PVD, CKD
COPD 30%(confounds the presenting symptoms dyspnea)
Atrial fibrillation 30-40% (can both precipitate AHF and
complicate its management)
clinical signs and
( congestion or end-
organ dysfunction, or
may be one of
1. In most patients with AHF, the original substrate is one
of chronic compensated heart failure, followed by
decompensation with development of AHF.
2. No previous history of heart failure but exhibit an
abnormal substrate (e.g., those with stage B heart
failure associated with asymptomatic LV dysfunction)
with a first presentation of heart failure (de novo heart
3. No previous history of heart failure in whom AHF
develops because of sudden changes in ventricular
function from an acute insult such as myocardial
infarction or acute myocarditis.
vary according to, and interact with, the underlying substrate
Maybe cardiac or extracardiac.
For patients with normal substrate (normal myocardium), a substantial
insult to cardiac performance (e.g., acute MI, myocarditis) is
required to lead to the clinical presentation of AHF.
For patients with abnormal substrate at baseline (e.g., asymptomatic LV
dysfunction), smaller perturbations (e.g., poorly controlled
hypertension, atrial fibrillation, or ischemia) may precipitate an
For patients with a substrate of compensated or stable chronic heart
failure, medical or dietary noncompliance, drugs such as
nonsteroidal anti-inflammatory agents or thiazolidinediones, and
infectious processes all are common triggers for decompensation.
Neurohormonal and inflammatory activation,
Ongoing myocardial injury with progressive
Worsening renal function,
Interactions with the peripheral vasculature
“all of which may contribute to the propagation and
worsening of the AHF episode”
Systemic or pulmonary congestion, most often the
result of a high LV diastolic pressure, dominates the
clinical presentation in most patients hospitalized for
Gradual increases in intravascular volume lead to
symptoms of congestion and clinical presentation, and
normalization of volume status with diuretic therapy
results in restoration of homeostasis. Although this
mechanism may be operative in some patients
(particularly those with frank noncompliance with
sodium restriction or diuretic therapy), this is
Increasing interest in the concept of
volume redistribution rather than volume retention
as a mechanism of decompensation in heart failure
Clinical congestion and hemodynamic congestion
Although patients present with signs and symptoms of
systemic congestion such as dyspnea, rales, elevated
jugular venous pressure, and edema, this state often is
preceded by so-called hemodynamic congestion,
defined as high LV diastolic pressures without overt
Similarly, clinical congestion may resolve with
treatment but hemodynamic congestion may persist,
leading to a high risk of rehospitalization.
hemodynamic congestion may contribute to the
progression of heart failure because it may result in:
(RAAS) and sympathetic nervous system (SNS) activation.
Myocyte loss and increased fibrosis.
Abnormal processing of the natriuretic peptides
Elevated diastolic filling pressures may decrease coronary
perfusion pressure, resulting in subendocardial ischemia
with further exacerbation of cardiac dysfunction.
Increased LV filling pressures also can lead to a more
shape, contributing to worsening mitral regurgitation.
Although a variety of extracardiac factors play
important roles in AHF, impairments of cardiac
function (systolic, diastolic, or both) remain central to
our understanding of this disorder.
Changes in systolic function and decreased arterial
filling can initiate a cascade of effects that are
adaptive in the short term but maladaptive when
elevated chronically, including stimulation of the
SNS and the RAA. (vasoconstriction, sodium and
water retention, increase and redistribution from
other vascular beds, increases in diastolic filling
In patients with underlying CAD, initial
defects in systolic function may initiate a
vicious circle of decreasing coronary
perfusion, increased myocardial wall
stress, and progressively worsening cardiac
performance. Increased LV filling pressures
and changes in LV geometry can worsen
functional mitral regurgitation, further
decreasing cardiac output.
Approximately half of patients with AHF have relatively
preserved systolic function.
Of importance, abnormalities in diastolic function are
present in patients with both preserved and impaired
The impairment of the diastolic phase may be related to
passive stiffness or abnormal active relaxation of the left
ventricle, or both.
Hypertension, tachycardia, and myocardial ischemia can
further impair diastolic filling. All of these mechanisms
contribute to higher LV end-diastolic pressures, which are
reflected back to the pulmonary capillary circulation.
Diastolic dysfunction alone may be insufficient to lead to
AHF, but it serves as the substrate on which other
precipitating factors (such as atrial fibrillation, coronary
artery disease, or hypertension) lead to decompensation.
The availability of sensitive assays for circulating cardiac
troponins has led to substantial evolution of our
understanding of the role of myocardial injury in the
pathophysiology of heart failure.
Circulating cardiac troponins are elevated in a large
proportion of patients with AHF, even in the absence of
clinically overt myocardial ischemia.
30% had persistent elevation of troponin at 30 days
Associated with increased risk of both in-hospital and
The precise mechanisms mediating myocardial injury in
Increased myocardial wall stress,
Increased myocardial oxygen demand,
Decreased coronary perfusion pressure,
Activation of the neurohormonal and inflammatory axes,
Activation of platelets,
Altered calcium handling.
All may contribute to myocyte injury even in absence of CAD
Specific therapeutic interventions that may increase myocardial
oxygen demand (such as positive inotropic agents) or decrease
coronary artery perfusion pressure (such as some vasodilators)
may exacerbate myocardial injury and further contribute to the
cycle of decompensation.
The kidney plays two fundamental roles relative to the
pathophysiology of heart failure:
1) Modulates loading conditions of the heart by controlling
2) Responsible for neurohormonal outputs (i.e., the RAAS system)
Baseline measures of renal function also are well-established risk
factors for poor outcomes in AHF
Additionally, worsening renal function during AHF therapy in the
setting of persistent congestion—often termed the “cardiorenal
syndrome”—has been associated with poor outcomes
Although often assumed to be related to low cardiac output and renal
blood flow, careful hemodynamic studies have confirmed that: “The
strongest predictor of worsening renal function in heart failure
patients relates to elevated central venous pressure, which is
reflected back to the renal veins and leads directly to changes in
glomerular filtration rate.”
Diuretics may exacerbate renal dysfunction through
increasing neurohormonal activation and vasoconstriction,
although in many cases effective diuresis improves renal
function by decreasing central venous pressure.
Newer biomarkers that may distinguish changes in renal
function (as reflected by serum creatinine or cystatin C)
from acute kidney injury (as reflected by markers such as
urinary neutrophil gelatinase– associated lipocalin
[NGAL]) may allow better differentiation of worsening
renal function during AHF hospitalization
Increasing appreciation for the importance of the vasculature
not only as an underlying cause of cardiac dysfunction (i.e.,
atherosclerosis, hypertension) but also as a central component of
the pathogenesis of AHF
Abnormalities of endothelial function related to nitric oxide–
dependent regulation of vascular tone
Peripheral vasoconstriction in the setting of AHF redistributes
blood centrally, increasing pulmonary venous congestion and
This increased afterload causes greater ventricular wall stress
and increased myocardial ischemia and cardiac
Effects of this vascular abnormality are amplified by LV
Neurohormonal and Inflammatory
Increased plasma concentrations of norepinephrine,
plasma renin activity, aldosterone, and endothelin-1 have
been reported in patients with AHF; all of these axes are
associated with vasoconstriction and volume retention, which
could contribute to myocardial ischemia and congestion, thereby
exacerbating cardiac decompensation.
Proinflammatory cytokines such as tumor necrosis
factoralpha and interleukin-6 are elevated in patients with AHF
direct negative inotropic effects on the myocardium as well as
increasing capillary permeability and inducing endothelial
Stimulates the release of the potent procoagulant tissue factor
and endothelin-1, which can lead to further myocardial
suppression, disruption of the pulmonary alveolar-capillary
barrier, and increased platelet aggregation and coagulation
(potentially worsening ischemia)
1. Decompensated heart failure:
This group is composed of patients with worsening
signs and symptoms of congestion on a background
of chronic heart failure.
may be acute, subacute, or indolent, with gradually
worsening symptoms over days to weeks.
Either preserved or reduced ejection fraction, but
cardiac output generally is preserved and blood
pressure is within the normal range.
Overall, this group represents the largest proportion
of patients hospitalized for AHF.
2. Acute hypertensive heart failure:
Hypertension is increasingly recognized as a common feature of the AHF
presentation, with 50% of patients presenting with systolic blood
pressure (SBP) higher than 140 mm Hg and 25% with SBP higher than
160 mm Hg.
hypertension may be triggered by a high sympathetic tone related to
dyspnea and accompanying anxiety (reactive hypertension)
OR acute hypertension with accompanying changes in afterload may
be a trigger for decompensation. Both of these mechanisms may be
operative in a given patient,
cause-and-effect relationships may be difficult to discern with
patients in whom acute hypertensive heart failure are more likely to
have preserved systolic function
Sudden onset of symptoms
Frank pulmonary edema with evident rales and florid congestion
on the chest radiograph is much more common in this group of
patients than in those with more gradual onset of symptoms, probably
related to differences in LV compliance, acuity of pressure changes, and
pulmonary lymphatic capacity.
3. Cardiogenic shock:
This group presents with signs and symptoms
of organ hypoperfusion despite adequate preload
SBP often (although not always) is decreased, and
evidence of frank or impending end-organ dysfunction
(renal, hepatic, central nervous system) is common.
This type of AHF is relatively uncommon (4% )
Less common AHF clinical scenarios as:
isolated right-sided heart failure
high-output heart failure
AHF Clinical Triggers:
In the OPTIMIZE-HF registry, 61% of enrolled subjects had an
identifiable clinical precipitant:
Arrhythmias (e.g. AF)
Worsening renal function was responsible for the highest in-
hospital mortality rate (8%),
Nonadherence to diet or medication OR
Uncontrolled HTN was associated with a much better
prognosis (<2% in-hospital mortality for each).
Others: Thyroid disease, Anemeia
More than one precipitant was identified in a substantial
minority of the study population.
The natriuretic peptides are a family of important counterregulatory hormones in
heart failure with vasodilatory and other effects
In AHF, both brain natriuretic peptide (BNP) and N-terminal pro–brain natriuretic
peptide (NT-proBNP) have an important role in the differential diagnosis in
patients presenting in the emergency department with dyspnea
BNP threshold of 100 pg/mL maximized sensitivity and specificity to
differentiate dyspnea that ultimately confirmed to be due to AHF:
the negative predictive value of a BNP level less than 100 pg/mL was particularly
the positive predictive value of this threshold was (79%)
NT-proBNP has similar diagnostic value, although the appropriate cut points
are higher overall and vary with age
False positives (e.g., caused by myocardial infarction or pulmonary embolism)
False negatives (primarily caused by obesity, which results in lower NP levels for a
given degree of heart failure)
Natriuretic peptide levels tend to be lower in patients with HFpEF than those with
reduced systolic function
MANAGEMENT OF THE PATIENT
WITH ACUTE HEART FAILURE
Establish the diagnosis,
Treat life-threatening abnormalities,
Initiate therapies to rapidly provide symptom relief,
Identify the cause and precipitating triggers.
General Approaches to Therapy of
Acute Heart Failure
The current general approach focuses on the
successful treatment of clinical and hemodynamic
congestion, while limiting effects on myocardial or
end-organ function, identifying addressable triggers,
and optimizing proven long-term therapies
Incorporates information from three main aspects of
the patient’s clinical presentation:
blood pressure, volume status, and renal function
1) Blood Pressure
Most patients present with elevated blood pressures
and consequently will benefit from and safely tolerate
Vasodilators may decrease preload by reversing
venous vasoconstriction and the related central
volume redistribution from the peripheral and
splanchnic venous systems, and reduce afterload
by decreasing arterial vasoconstriction with a
resultant improvement in cardiac and renal function.
Hypotension (SBP below 85 to 90 mm Hg) is a poor
prognostic sign in patients with AHF.
Asymptomatic hypotension, as an isolated finding in the
absence of congestion and poor peripheral or central
perfusion, does not require emergent treatment.
Inotropic therapy may be indicated for persistent
symptomatic hypotension or evidence of hypoperfusion in
the setting of advanced systolic dysfunction.
In general, the use of vasoconstrictors, such as highdose
dopamine, phenylephrine, epinephrine, and
norepinephrine, should be avoided unless such agents are
absolutely necessary for management of refractory
symptomatic hypotension or hypoperfusion
2) Volume Status
Most patients with AHF have evidence of volume overload
Intravenous diuretics remain the foundation of AHF
Patients with clinically evident congestion typically have 4
to 5 liters of excess volume, and amounts greater than 10 L
are not uncommon.
The choice of diuretic regimen is influenced by the
amount and rapidity of the desired fluid removal and the
Diuresis addresses the underlying abnormality and
frequently alleviates symptoms and signs of elevated filling
However, intravenous vasodilator therapy may provide
more rapid relief in highly symptomatic patients with
evidence of pulmonary congestion. In fact, many patients
with hypertensive AHF may require minimal diuretics.
Careful attention to volume status is critical, because
patients’ symptoms of congestion may resolve despite
persistent hemodynamic congestion (i.e., elevated filling
Hospital discharge before hemodynamic congestion is fully
treated appears to be a common cause of rehospitalization
3) Renal Function
Approximately two thirds of patients present with at
least moderate renal insufficiency.
This deficit may reflect preexisting kidney disease or may
be a manifestation of the worsening heart failure.
Abnormal renal function typically is associated with some
degree of diuretic resistance, and higher doses of diuretics or
other strategies may be needed.
The important clinical problem of worsening renal
function during AHF therapy, the cardiorenal syndrome
Loop diuretics are the primary pharmacologic agents for treatment
of volume overload in patients with AHF
Rapid symptom relief in most patients
This group of agents (furosemide, torsemide, bumetanide, and ethacrynic acid)
intravenous administration avoids variable bioavailability and allows for rapid onset of
action (typically within 30 to 60 minutes)
Based on the results of the DOSE study, initial doses of approximately 2.5 times
the outpatient dose should be considered for patients on chronic oral
diuretic therapy, with underlying renal dysfunction, or with severe volume overload.
Titration should be rapid with doubling of the dose until an effective
response is noted.
With significant volume overload (>5 to 10 liters) or diuretic resistance,
a continuous intravenous infusion can be considered.
In the absence of hypotension, vasodilators can be used as first-line agents in
combination with diuretics in the management of patients with AHF to
improve congestive symptoms
Include the organic nitrates (nitroglycerin [NTG] and isosorbide dinitrate),
sodium nitroprusside (SNP), and nesiritide.
All of these drugs act by activating soluble guanylate cyclase (sGC) in the
smooth muscle cells, leading to higher intracellular concentrations of cyclic
guanosine monophosphate (cGMP) and consequent vessel relaxation
used with caution in patients who are preload- or afterload-dependent (e.g.,
severe diastolic dysfunction, aortic stenosis, coronary artery disease),
because they may cause severe hypotension.
Blood pressure (BP) should be monitored frequently and the drug
discontinued if symptomatic hypotension develops.
Organic nitrates are one of the oldest therapeutic
agents for management of AHF.
These agents are potent venodilators, producing
rapid decreases in pulmonary venous and ventricular
filling pressures and improvement in pulmonary
congestion, dyspnea, and myocardial oxygen demand
at low doses
At slightly higher doses and in the presence of
vasoconstriction, nitrates also are arteriolar
vasodilators, reducing afterload and increasing cardiac
Nitrates are relatively selective for epicardial, compared to
intramyocardial, coronary arteries, resulting in increased
coronary blood flow and making them useful for patients with
concomitant active myocardial ischemia.
Organic nitrates may also be administered orally, sublingually,
or by spray, allowing for convenient emergent treatment
before establishing intravenous access
The dose may initially be titrated to the goal of immediate
symptom relief, but a blood pressure reduction of at least 10
mm Hg in mean arterial pressure with a SBP greater than 100
mm Hg may be preferable.
The nitrate dose may need to be reduced if SBP is 90 to 100
mmHg and often will need to be discontinued with SBP below
90 mm Hg.
Limitations of organic nitrates:
Tolerance that typically develops within 24 hours
Headache is the most common adverse effect (20%)
Symptomatic hypotension (5%) but generally resolves
when nitrate therapy is discontinued.
In view of the risk of severe hypotension with
potentially catastrophic consequences, the recent use
of phosphodiesterase-5 inhibitors (sildenafil, tadalafil,
and vardenafil) should be ruled out before
administration of nitrates
In patients with severe hypoxemia (oxygen saturation
[SaO2] <90%), oxygen administration is
Although oxygen saturation on presentation is inversely
related to short-term mortality, inhaled oxygen (FiO2 ≥0.4)
may cause detrimental hemodynamic effects (such as
hyperoxia-induced vasoconstriction) in patients with
systolic dysfunction, so it is not routinely recommended
for patients without hypoxemia.
In patients with obstructive pulmonary disease, high
concentrations of inhaled oxygen should not be used, to
avoid the risk of respiratory depression and worsening
(NIPPV) & (CPAP)
Noninvasive ventilation (NIV) with continuous
positive airway pressure(CPAP) or noninvasive
intermittent positive-pressure ventilation(NIPPV) was
associated with greater improvement in patient-
reported dyspnea, heart rate, acidosis, and
hypercapnea after 1 hour of therapy,
although it was not associated with a 7-day mortality
benefit or with decreased need for intubation when
compared with standard oxygen therapy.
CPAP CPAP typically is initiated with a positive end-expiratory pressure
5 to 7.5 cm H2O, titrated to 10 cm H2O as needed for dyspnea relief
and improvement in O2 saturation.
immediate need for endotracheal intubation (inability to protect the
airway, life-threatening hypoxia)
lack of patient cooperation (altered sensorium, unconsciousness,
anxiety, inability to tolerate mask)
Caution is indicated in patients with :
Cardiogenic shock, RV failure, and
Severe obstructive airway disease.
Potential side effects and complications
anxiety, claustrophobia, dry mucous membranes,
worsening RV failure, hypercapnea, pneumothorax, and aspiration
Morphine may be useful in patients with severe
anxiety or distress but should be used cautiously or
avoided, especially in the presence of hypotension,
bradycardia, advanced atrioventricular block, or CO2
Morphine use has been associated with increased
likelihood of mechanical ventilation, requirement
for intensive care unit (ICU) admission, prolonged
hospital stay, and death