Download Algorithm for therapeutic management of acute heart failure

Heart Fail Rev (2007) 12:113–117
DOI 10.1007/s10741-007-9013-6
Algorithm for therapeutic management of acute heart failure
syndromes
Ramzi Chatti Æ Nabil Ben Fradj Æ Wissem Trabelsi Æ
Hakim Kechiche Æ Miguel Tavares Æ
Alexandre Mebazaa
Published online: 18 April 2007
Ó Springer Science+Business Media, LLC 2007
Abstract As for other critically ill diseases, two key
factors may markedly improved morbidity and mortality of
acute heart failure syndromes (AHFS): early initiation of
treatment and tailored therapy. Early initiation aims to stop
the negative cascade of heart dysfunction. Tailored therapy
should be based on the level of systolic blood pressure at
admission and fluid retention. Indeed, EFICA and OPTIMIZE-HF showed that patients with high systolic blood
pressure have a left ventricular systolic function that is
likely preserved and those with low systolic blood pressure
have a lower left ventricular ejection fraction and frequent
signs of organ’s hypoperfusion. Among the proposed
treatments, non-invasive ventilation is the only treatment
that was consistently proven to be beneficial on morbidity
and mortality in almost all types of AHFS. Concerning
pharmacological agents, actions should be taken to increase
the use of vasodilators and reduce the use of diuretics.
Keywords Acute heart failure Non-invasive ventilation Levosimendan Nitrates Diuretics
Acute heart failure syndromes: definitions
In most textbooks of cardiology or intensive care, in the
last 40 years, acute heart failure is considered as a mixture
including an acute pulmonary edema following an increased arterial blood pressure and a cardiogenic shock
related to acute myocardial infarction. The word ‘‘heart’’
in ‘‘acute heart failure’’ is indeed confusing. Many young
physicians still believe that during an acute heart failure
episode, the heart, and specially its systolic function is
impaired; as described in this review, we know today that
this is not true [1, 2]. In addition, as pulmonary edema was
described in the 50’s in patients with long history of heart
failure, named ‘‘congestive heart failure’’ for years, physicians had the impression that pulmonary edema is always
associated with increased volemia and that pulmonary
edema should be always treated with diuretics. However,
we know today that most episodes of acute pulmonary
edema appear in patients with long history of hypertension
and are rather euvolemic [2].
Definitions based on physiopathology
R. Chatti N. B. Fradj W. Trabelsi H. Kechiche M. Tavares A. Mebazaa (&)
Department of Anesthesiology and Critical Care Medicine,
Lariboisière Hospital, University Paris 7 Denis Diderot,
2 Rue Ambroise Paré, Paris 75010, France
e-mail: [email protected]
M. Tavares
Department of Anesthesiology and Critical Care, Hospital Geral
de Santo António, Porto, Portugal
In order to classify patients admitted with acute heart
failure syndromes (AHFS), Heart Failure Society of
America and the European Society of Cardiology recently
defined categories based on physiopathological concepts.
Heart Failure Society of America distinguished patients
in three categories [3]: (1) the majority of patients hospitalized with acute heart failure have evidence of systemic
hypertension on admission and commonly have preserved
left ventricular ejection fraction (LVEF); (2) most hospitalized patients have volume overload and congestive
symptoms; (3) a distinct minority with severely impaired
systolic function, reduced blood pressure and symptoms
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from poor end-organ perfusion. The European Society of
Cardiology and the European Society of Intensive Care
Medicine further classified acute heart failure patients in
six categories [4]: (1) Hypertensive acute HF: signs and
symptoms of HF are accompanied by high blood pressure
and relatively preserved left ventricular function with a
chest radiograph compatible with acute pulmonary edema;
(2) Pulmonary edema accompanied by severe respiratory
distress, with crackles over lung orthopnea, with O2 saturation usually <90% on room air before treatment; (3)
Acute decomposed HF (de novo or as decomposition of
chronic HF): signs and symptoms of acute HF that are mild
and do not fulfill the criteria for cardiogenic shock, pulmonary edema, or hypertensive crisis; (4) Cardiogenic
shock: cardiogenic shock is defined as evidence of tissue
hypoperfusion induced by HF after correction of preload.
There is no clear definition for hemodynamic parameters,
but cardiogenic shock is usually characterized by reduced
blood pressure (systolic blood pressure <90 mmHg or a
drop of mean arterial pressure >30 mmHg) and/or low
urine output (<0.5 ml /kg per hr), with a pulse rate >60
beats per min with or without evidence of organ congestion. There is continuum from low cardiac output syndrome
to cardiogenic shock; (5) High output failure is characterized by high cardiac output usually with high heart rate
(caused by arrhythmias, thyrotoxicosis, anemia, Paget’s
disease, or iatrogenic or other mechanisms), with warm
peripheries, pulmonary congestion, and sometimes low
blood pressure, as in septic shock; (6) Right HF is characterized by low output syndrome with increased jugular
venous pressure, increased liver size, and hypotension.
This is the basis of the ‘‘new’’ concept of ‘‘Acute Heart
Failure Syndromes’’. These categories have been shown to
also represent different outcomes: hypertensive acute pulmonary edema has a lower mortality rate compared to
decompensated heart failure or cardiogenic shock [2]. In
addition, outcome is likely different when AHFS appears
de novo or in a context of decompensated heart failure [5].
Definitions based on blood pressure at admission
Although, the classifications proposed by HFSA and ESC
were an important first step to categorize AHFS patients, it
rapidly appeared that one should use a classification that
can be used by any physician, including junior physicians,
in charge of AHFS in several settings such as emergency
room.
Systolic blood pressure (SBP) is shown increasingly as
the main predictor of both morbidity and mortality. The
French study EFICA studied 581 patients admitted with
AHFS in CCU/ICU. In the group of patients without cardiogenic shock (n = 415), patients with SBP > 160 mmHg
on admission (n = 90) had a lower four-week mortality rate
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Heart Fail Rev (2007) 12:113–117
than patients with SBP < 160 mmHg (n = 325) (7% versus
17% respectively, P = 0.03) [2]. Similar difference in
mortality was observed between the two subgroups at
1 year. Of note, patients with high SBP are similar to those
described in other surveys: old with a history of hypertension, ECG and echocardiographic signs of LV hypertrophy and preserved LVEF.
Recently, a study (OPTIMIZE-HF) enrolled 48,612 patients between March 2003 and December 2004 from 259
hospitals across the United States [1]. The major determinant of long-term mortality was systolic blood pressure.
Patients were categorized into quartiles based on their
admission SBP values: SBP < 120 mmHg; SBP in the
range of 120–139 mmHg; SBP in the range of 140–
161 mmHg; SBP > 161 mmHg. More patients in the
higher SBP quartiles (140–161 mmHg and >161 mmHg)
had preserved systolic function and were black. The inhospital mortality rate was 3.8% in the entire cohort and
the mean length of stay was 6.4 days. Higher SBP at
admission was associated with substantially lower in-hospital mortality: 7.2% (<120 mmHg), 3.6% (120–
139 mmHg), 2.5% (140–161 mmHg), and 1.7%
(>161 mmHg) (P < .001 for overall difference) and 60–
90 day mortality.
Treatment of acute heart failure syndromes tailored
therapy
Based on the both surveys, EFICA and OPTIMIZE-HF, we
suggest that the treatment algorithm of AHFS patients
should be based on the level of SBP at admission (Fig. 1).
Two SBP cut-offs are proposed in this algorithm: 100 and
140 mmHg. Indeed, as described above, at SBP of
>140 mmHg, left ventricular systolic function is likely
preserved, at SBP of 100–140 mmHg left ventricular systolic function is limited, and many patients with impaired
left ventricular systolic function exhibit SBP < 100 mmHg.
Patients with high systolic blood pressure are usually treated with diuretics and vasodilators such as nitroglycerin,
nitroprusside, nesiritide; while patients with AHFS and low
systolic blood pressure have a lower left ventricular ejection
fraction, frequent signs of organ’s hypoperfusion and are
more likely to receive inotropes.
Above all, the only treatment was consistently proven to
be beneficial on morbidity and mortality in almost all types
of AHFS is non-invasive ventilation.
Non-invasive ventilation (NIV)
Non-invasive respiratory support (=non-invasive ventilation, NIV) can be instituted early in AHFS, and it can be
Heart Fail Rev (2007) 12:113–117
Fig. 1 Algorithm for
therapeutic management of
acute heart failure syndromes.
This algorithm should be apply
within minutes of admission.
PAC: pulmonary artery catheter
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Assessments
•Non-invasive monitoring (SpO2, BP)
•O2
•Non-invasive ventilation (NIV) as indicated
•Lab tests
•BNP or NT-pro BNP, when diagnosis is uncertain
•ECG
•CXR
•Temperature
If SBP > 140 mmHg
If SBP 100-140 mmHg
If SBP < 100 mmHg
NIV + Nitrates
NIV + Nitrates
+ diuretics
Fluid challenge
+ inotropes
+ vasopressors
avoid diuretics
unless obvious
volume overload
provided by either CPAP (continuous positive airway
pressure) or bi-level ventilation (both inspiratory and
expiratory support, BiPAP). NIV augments cardiac output,
decreases left ventricular after load, increases functional
residual capacity and respiratory mechanics and reduces
the work of breathing.
A total of 23 clinical trials and three meta-analyses have
assessed the comparison among CPAP, BiPAP and standard therapy, or CPAP and BiPAP [6–8]. Nearly all revealed that both CPAP and BiPAP reduce the need of
intubations and reduces mortality in patients with acute
cardiogenic pulmonary edema. Some risk factors for intubation have been described in patients treated with conventional therapy: severe acidosis (pH < 7.25),
hypercapnia, acute myocardial infarction, low blood pressure, and severely depressed ventricular function.
Based on these data, early use of NIV should be considered for the early management of all AHFS patients
when dyspnea, respiratory distress, and/or pulmonary
edema are present to prevent the need for intubation, its
subsequent complications, and potentially, to reduce the
risk of mortality. NIV requires minimal nursing resources;
however, patient cooperation is necessary. A positive
pressure of 5–7.5 cm H2O titrated to clinical response is
the most appropriate initial therapy when CPAP is used.
Any hospital receiving AHFS patients should have an
adequate number of CPAP devices available.
Vasodilators
Based on registry data, the large majority of AHFS patients
present with signs of increased left ventricular filling
pressure, high or normal blood pressure and preserved left
ventricular systolic function; only a minority present with
low blood pressure or cardiogenic shock. Patients with high
SBP are ideal candidates for early initiation of vasodilator
therapy. Acute therapy with vasodilators can improve both
hemodynamics and symptoms. Currently available
volume overload is
possible
PAC if no improvement
vasodilators include nitrates, nitroprusside, and nesiritide.
In AHFS, intravenous nitroglycerin is preferred [4]. The
initial recommended dose is 10–20 lg/min, and it is increased in increments of 5 lg/min forevery 3–5 min as
needed. Tachyphylaxis is common, necessitating incremental dosing. The major adverse effects of nitrates are
hypotension (mean blood pressure should remain
>70 mmHg) and headache. Nesiritide, a recombinant form
of human B-type natriuretic peptide, is a venous and
arterial vasodilator that may also potentiate the effect of
diuretics. It is given intravenously as a 2 lg/kg bolus followed by a 0.01 lg/kg/min infusion. In the VMAC trial,
nesiritide lowered PCWP significantly more than either
intravenous nitroglycerin or placebo at the 3-h time-point,
and it improved dyspnea compared to placebo but not
compared to nitroglycerin [9].
Diuretics
Surveys indicate that loop diuretics are the first line agent
around the world for the treatment of patients with AHFS.
This is a paradox. Indeed, the most frequent AHFS clinical
scenario includes patients with high systolic blood pressure. Although edema is present in the lungs, those patients
are often normo- or even hypovolemic. As increasingly
described, AHFS associated to high blood pressure is
mostly seen in female old patients with history of systemic
hypertension. Those patients are often treated with oral
diuretics and are very likely normo- or hypovolemic at the
time they are admitted for AHFS. The latter is related to a
sudden increase in systolic blood pressure that induces
pulmonary edema because of a hypertrophied stiff left
ventricle. High dose diuretics in these patients may be
detrimental. Of note, only a few studies have evaluated
short and long-term clinical outcomes.
Appropriate early diuretic use might however be considered in patients with worsening chronic fluid overload.
This profile can be suspected based on the patient’s history,
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clinical examination (signs of congestion), signs of right
ventricular congestion, symptom severity (moderate
decompensation, pulmonary edema, or cardiogenic shock),
and blood pressure. Thus, recognizing the appropriate patient profile is important, and it will help to guide the
physician’s early management strategy.
Parameters for adjusting diuretic therapy have not been
established. In general, the lowest dose should be used that
produces the desired clinical effect. In chronic heart failure,
diuretic therapy is titrated according to fluid balance and
the resolution of signs and symptoms. The onset of diuresis
may not occur until 30–120 min after administration; thus,
urine output alone is not an ideal therapeutic target.
Dyspnea, global patient status, respiratory rate, oxygen
saturation, or needs for intubation are better targets, especially in critically ill patients.
In summary, aggressive diuretic monotherapy is not
necessary in the majority of patients. Diuretics should be
left only when there is evidence of systemic volume
overload. Effects of diuretics must be reassessed after 30–
60 min.
Cardiac enhancers and vasoconstrictors
Inotropes are a traditional component of the AHFS treatment strategy. The most common inotropes in clinical
practice include dobutamine and milrinone, but dopamine
is also available. Traditional inotropes are no longer recognized as first line, acute therapy for the majority of
AHFS patients, and data from ADHERE, OPTIMIZE, and
Euro Heart Failure Survey II indicate that traditional inotropes are used in approximately 10% of AHFS admissions
[1, 5, 10, 11]. The OPTIME-CHF study found no benefit
for milrinone in 949 patients hospitalized for worsening
heart failure [1, 2]. A higher risk of arrhythmias was observed, and patients with ischemic etiology who were
randomized to milrinone had worse outcomes.
However, early use of inotropic therapy may be appropriate in patients presenting in cardiogenic shock or with
evidence of low output who are not responding to other
therapies. These patients may include those with
SBP < 85–90 mmHg or evidence of organ hypoperfusion
including patients who are cold, clammy, or vasoconstricted. Renal impairment, liver dysfunction, or impaired
mentation are also possible signs of hypoperfusion. As
discussed, these patients account for the minority of AHFS
hospitalizations. Inotropes may stabilize patients at risk of
progressive hemodynamic collapse or serve as a life-sustaining bridge to more definitive therapy such as mechanical circulatory support, ventricular assist devices, or
cardiac transplant. Norepinephrine is recommended alone
or in combination with an inotrope or cardiac enhancer in
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order to increase SBP in the situation of persistent organ
hypoperfusion (e.g., low urine output clearly related to low
blood pressure). Epinephrine is however not recommended
as first line therapy; it is rather used as rescue therapy in
cardiac arrest. There is no evidence of a renal benefit with
low-dose dopamine.
Levosimendan is a novel calcium-sensitizer that improves cardiac contractility by binding to troponin-C in
cardiomyocytes. The significant vasodilatory properties of
levosimendan are mediated through ATP-sensitive potassium channels, causing peripheral arterial and venous
dilatation, and increasing coronary flow reserve [12].
Levosimendan has beneficial hemodynamic and clinical
effects in patients with AHFS, and it is safe in acute coronary syndrome. In the REVIVE trial, levosemindan significantly improved a composite of clinical signs and
symptoms of AHFS as compared to placebo over five days
as assessed by patients and their physicians [13]. In the
SURVIVE study comparing levosimendan and dobutamine, a statistically significant improvement in survival for
levosimendan treated patients was seen early, especially in
patients chronically treated with a beta blocker and in patients with prior heart failure, but it was not evident in 180day survival [14].
Why should we promote an early treatment of AHFS?
ADHERE registry data indicate that AHFS treatments are
often instituted more than 8 h after presentation. The mean
time to IV diuretics was 8 hours and the mean time to IV
vasoactive therapy was roughly 24 h [11, 15]. Starting
earlier the appropriate therapy may be a method to counteract negative effects (1) of AHFS, including hypoxemia,
hypotension and (2) of the drugs given to the patients,
before irreversible damage has occurred.
Nguyen et al. prospectively studied the impact of
emergency department (ED) intervention on physiologic
scores in 81 patients who presented to the ED with illnesses
severe enough to warrant ICU admission [16]. The data
from this study indicated that ED intervention might have
influenced the progression of critical illnesses. A similar
study in patients with severe sepsis or septic shock also
demonstrated improved clinical outcomes with early goaldirected therapy [17].
These data suggest that early initiation of treatments
for AHFS may be a key factor in improving outcomes
among critically ill patients [17–19]. We are proposing
here that treatment algorithm should be based on systolic
blood pressure at admission. Among the proposed treatments, non-invasive ventilation is the only treatment that
was consistently proven to be beneficial on morbidity and
mortality in almost all types of AHFS. Concerning
Heart Fail Rev (2007) 12:113–117
pharmacological agents, actions should be taken to increase
the use of vasodilators and reduce the use of diuretics.
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9.
Acknowledgement Financial support: Ministère de l’Enseignement Supérieur et de la Recherche (EA 322).
10.
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