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S Afr Fam Pract
ISSN 2078-6190    EISSN 2078-6204 

© 2019 The Author(s)

REVIEW

Introduction

Heart failure is regarded as a heterogeneous syndrome of 
symptoms such as dyspnoea, orthopnoea, oedema of ankles, 
fatigue/limited exercise capacity, and signs such as elevated 
jugular venous pressure, pitting oedema, crackles in the lung 
and a gallop heart rhythm. The heart itself has a structural or 
functional abnormality leading to elevated intracardiac pressures 
or reduced cardiac output at rest or during effort.1 

Importantly, acute heart failure may comprise distinct entities 
with different pathophysiologies, treatments and clinical 
outcomes. Currently two different phenotypes, including new 
onset acute heart failure and recurrent or severe worsening of 
existing previously well-controlled heart failure, are encountered. 
Most patients with acute new-onset heart failure present to a 
primary health care provider or an emergency room facility with 
acute dyspnoea, fatigue and occasionally swollen legs, the latter 
more common in acute exacerbations of chronic heart failure. 
People with acute heart failure have a poor prognosis with high 
rates of hospital admission that carry mortality rates of 25% 
or more per year.2 In fact, in-hospital mortality of acute heart 
failure can be greater than that of acute myocardial infarction, 
and mortality remains high for more than a year after discharge 
compared to stable outpatient heart failure.3 Early readmission 
within 30–90 days after discharge is common, affecting almost 
one quarter of acute heart failure patients. The clinical course 
and prognosis of chronic heart failure patients who have an 
acute episode of heart failure is worse.4 One study demonstrated 
that although the 30-day mortality between the two phenotypes 
was the same, the 1-year mortality was significantly higher in the 
acute exacerbation group.5 

Most patients present with congestion, predominantly 
pulmonary (crackles), peripheral oedema and elevated jugular 
venous pressure. Poor perfusion due to low cardiac output is 
seen in about 5% of acute heart failure cases. Renal dysfunction, 
due to a multitude of mechanisms, but mainly due to elevated 
central venous pressure increasing afterload on the kidneys is 

usually associated with a poor outcome. Declining renal function 
accompanied by persistent congestion despite treatment has a 
bleak outlook, and this combination presents a dilemma for 
the clinician: limiting diuretics to preserve renal function may 
prolong congestion, whereas aggressive diuresis may worsen 
renal dysfunction. Cardiac biomarkers that remain elevated, such 
as troponins, natriuretic peptides and transaminases, correlate 
with poor survival.1

Therapeutic approach

Clinical congestion

Decongestive therapy is the major goal in acute heart failure 
management to control clinical congestion such as dyspnoea 
and oedema.6 As there is a paucity of hard evidence, the 
pharmacotherapy of acute heart failure remains largely 
empiric and consensus-driven.1 Intravenous administration 
of furosemide, torsemide or bumetanide is recommended to 
relieve congestion, and these potent loop diuretics are the 
mainstay of treatment. There appears to be no real difference 
in outcomes between intermittent intravenous doses of a loop 
diuretic versus continuous infusions, but it has been shown that 
the earlier intravenous diuretic is initiated, the better the in-
hospital mortality.7,8

Haemodynamic congestion

This phase of congestion usually occurs without clinical signs 
of congestion but with elevated pulmonary wedge pressures 
and elevated N-terminal pro-brain-type natriuretic peptide (NT-
proBNP) levels, the latter much easier for a clinician to evaluate.9

If cardiogenic shock is present then mechanical and 
pharmacological circulatory support including non-invasive 
positive pressure support is necessary for survival.

Intravenous therapy for all

a. Systolic blood pressure > 100 mmHg: This pragmatic cut-off 
blood pressure indicates possible early danger to the kidney. 
In practice, it denotes a level above which only a diuretic is 

In general, heart failure is the end-stage manifestation of cardiovascular disease and is an important and increasing cause of 
morbidity worldwide. Acute heart failure, whether of new onset or an exacerbation of chronic heart failure, causes sudden 
congestion, typically presenting as pulmonary oedema. The mortality associated with acute heart failure is extremely high. 
Potentially life-saving treatments and other burning issues are highlighted in this review.

Keywords: Acute heart failure, pulmonary oedema, N-terminal pro-brain-type natriuretic peptide (NT-proBNP), loop diuretics, 
ivabradine, angiotensin receptor-neprilysin inhibitor (ARNI)

South African Family Practice 2019; 61(6):6-8
 
Open Access article distributed under the terms of the 
Creative Commons License [CC BY-NC-ND 4.0] 
http://creativecommons.org/licenses/by-nc-nd/4.0

Burning issues in acute heart failure management 
JA Ker,1 K Outhoff2 

1 Department of Internal Medicine, School of Medicine, Faculty of Health Sciences, University of Pretoria, South Africa 
2 Department of Pharmacology, School of Medicine, Faculty of Health Sciences, University of Pretoria, South Africa 
Corresponding author, email: kim.outhoff@up.ac.za



Burning issues in acute heart failure management 7

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necessary. Therefore, administer intravenous diuretics, by 

either bolus or constant infusion, as there seems to be no 

difference in response between these regimens. The response 

goal of diuretic therapy is a urine output of 3–5 litres daily 

until euvolemia is reached. There is a convenient stepped-

care approach to diuretic dosing in acute heart failure, which 

is dependent on the level of previous diuretic use (see Table 

I).10 Vasodilator therapy is also part of treatment in this group 

of patients with relatively elevated blood pressures, especially 

in those with systolic blood pressures of 140 mmHg or higher.  

b. Systolic blood pressure < 100 mmHg: Administer either 

diuretics if congestion is present, or intravenous fluid if there 

are no signs of congestion. Inotropes are recommended if 

there is no response to the intravenous fluid challenge. The use 

of inotropes has been of concern due to their association with 

increased mortality as shown in the Acute Decompensated 

Heart Failure National Registry (ADHERE).11 Despite these 

concerns, short-term positive inotrope therapy (dobutamine) 

is often unavoidable, especially when the systolic blood 

pressure is below 90 mmHg.12  Vasopressors are used if there is 

no response to inotropes.

Identify and treat significant co-morbidities

Several co-morbidities have been shown to contribute to the 

development and exacerbation of heart failure with reduced 

ejection fraction (HFrEF) specifically. These conditions include 

coronary artery disease, hypertension, myocardial disease, 

pericardial disease, cardiac electrical abnormalities (atrial 

fibrillation of specific worse outcome), valvular disease, renal 

disease, iron deficiency, lung disease (especially COPD with 

patients complaining of dyspnoea), diabetes mellitus and as well 

as non-adherence to treatment.13 

Avoid potentially harmful therapies 

A study has shown that when 1 litre of normal saline is given 

early in the treatment of acute heart failure compared to 

intravenous diuretic only, there is an increased risk of intubation, 

ICU admission and mortality. Opiates are also generally avoided 

because of their adverse effects on respiratory and cognitive 

function. Calcium channel blockers due to their negative 

inotropic properties should not be used. Other drugs to avoid 

in acute heart failure include antiarrhythmic drugs (except 

amiodarone), nonsteroidal anti-inflammatory drugs, and any 

drug that has an effect on renal function.

Therapy on discharge from hospital to prevent readmission

a. A pre-discharge NT-proBNP level is useful for determining 
prognosis and is recommended by guidelines.14 Patients 
with an NT-proBNP decline of > 50% from hospital admission 
to pre-discharge had a similar mortality to those admitted 
with low levels of NT-proBNP in the ASTRONAUT study.15 
Soluble suppression of tumorigenicity 2 (ST2), a biomarker 
of cardiac stress, and the tumour marker cancer antigen 125 
(CA125), widely used in ovarian cancer therapy monitoring, 
are increased in heart failure patients with effusions, ascites 
and peripheral oedema and are therefore increasingly used as 
biomarkers in heart failure. In future, they may prove useful as 
prognostic markers.

b. Planning and considering prevention of readmission 
strategies after discharge from hospital is essential as about 1 
in 4 patients are readmitted within 30–90 days.15

c. Continue the use of or begin therapies known to decrease 
hospital readmissions.13 It has been shown that initiation 
of guideline-directed-medical-therapy of heart failure in 
hospital rather than post-discharge leads to higher adherence 
to prescribed medications, at least for 60 days of follow-up 
evaluations.

Temporary further worsening of renal function caused by 
decongestive therapy or initiation of renin-angiotensin-
aldosterone-system (RAAS) inhibitors is associated with 
cessation of proven angiotensin converting enzyme inhibitor 
(ACE-inhibitor) or angiotensin receptor blocker (ARB) 
medications, which then negatively affects not only prognosis, 
but also readmissions due to worsening heart failure. Do not 
stop these drugs and initiate them if not already in use.

Digoxin use is associated with a reduction in hospitalisation, 
but not improved mortality, and can be used for the purpose 
of reduced hospitalisations. 

Torsemide could be a more effective diuretic as it has a better 
bioavailability and longer duration of action. The ongoing 
TRANSFORM-HF trial is comparing it to furosemide to 
determine clinical outcomes.

A thiazide diuretic added to furosemide is an important 
method to potentiate the action of the loop diuretic in 
controlling congestion, which is a critical issue as it determines 
prognosis.

Mineralocorticoid receptor antagonists have also been shown 
to be underused in pre-discharge of patients with acute heart 
failure. These drugs reduce mortality in heart failure with 

Table I. Recommended intravenous loop diuretic dosing in acute heart failure with systolic blood pressure > 100 mmHg

Level Previous oral dose of 
furosemide*

Administer intravenous 
furosemide* bolus 

Followed by furosemide* 
infusion mg/hour

Add hydrochlorothiazide 
(HCTZ) if poor response

Level 1  < 80 mg 40 mg bolus 5 mg/hour

Level 2 81–160 mg 80 mg bolus 10 mg/hour 50 mg twice daily

Level 3 161–240 mg 80 mg bolus 20 mg/hour 50 mg twice daily

Level 4 > 240 mg 80 mg bolus 30 mg/hour 50 mg twice daily

* Furosemide 40 mg is equivalent to bumetanide 1 mg or torsemide 20 mg



S Afr Fam Pract 2019;61(6):6-88

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reduced ejection fraction and may even be of value in those 
with preserved ejection fraction.

Ivabradine, the selective sinoatrial node inhibitor, has been 
shown to reduce hospital readmissions and death in patients 
with low ejection fraction heart failure with a resting heart rate 
of more than 70 beats/minute on beta-blockers in the SHIFT 
trial. 

d. Initiation of the combination of the ARB, valsartan, plus the 
neprilysin-inhibitor, sacubitril, led to a greater reduction in 
NT-proBNP levels compared to enalapril in patients with 
heart failure admitted to hospital due to acute worsening 
of heart failure in the PIONEER trial.16 The rates of worsening 
renal function, hyperkalaemia, symptomatic hypotension 
and angioedema did not differ significantly between the 2 
groups. This angiotensin receptor-neprilysin inhibitor (ARNI) 
combination was initiated at a low dose (suggested 50 mg 
twice daily) in patients who had the following criteria: systolic 
blood pressure ≥ 100 mmHg, no ACE-inhibitor or ARB for at 
least 36 hours, no increasing dose of intravenous diuretic for 6 
hours, no vasodilators for preceding 6 hours, and no inotropes 
for the preceding 24 hours. In the PARADIGM-HF randomised 
trial, ARNI reduced important clinical outcomes including 
mortality significantly more than enalapril in heart failure with 
reduced ejection fraction.17

Concluding summary

1. Acute heart failure often presents to an emergency facility, 
either de-novo or due to acute worsening of previous stable 
chronic heart failure.

2. Congestion is the main clinical problem.

3. Intravenous diuretic therapy is the mainstay of treatment.

4. It is important not to stop proven life-saving therapies, and 
if patients are not already receiving them, to initiate them, 
including the new ARNI combination, prior to discharging the 
patient.

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