Chronic Congestive Heart Failure

Chronic congestive
heart failure
Straight to the point of care
Last updated: Jun 16, 2021

Table of Contents
Overview 3
Summary 3
Definition 3
Theory 4
Epidemiology 4
Aetiology 4
Pathophysiology 5
Classification 6
Case history 7
Diagnosis 9
Approach 9
History and exam 10
Risk factors 12
Investigations 17
Differentials 22
Criteria 24
Screening 25
Management 26
Approach 26
Treatment algorithm overview 33
Treatment algorithm 36
Emerging 66
Primary prevention 68
Patient discussions 68
Follow up 69
Monitoring 69
Complications 70
Prognosis 71
Guidelines 72
Diagnostic guidelines 72
Treatment guidelines 73
Online resources 76
Evidence tables 77
References 80
Disclaimer 105
Chronic congestive heart failure Overview
Summary
Chronic congestive heart failure is a complex clinical syndrome that can result from any structural or
functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood.
OVERVIEW
It is a major and growing public health problem. It is the only cardiovascular disease that is increasing
in incidence and prevalence, partly because the population is ageing, but also because of improved
cardiovascular interventions for disease processes that reduce early mortality but may result in cardiac
changes that lead to heart failure.
The key manifestations are dyspnoea and fatigue, which may limit exercise tolerance, and fluid retention,
which may lead to pulmonary congestion and peripheral oedema.
Diagnosis is largely clinical; a thorough history and physical examination should be obtained to identify
cardiac and non-cardiac disorders or behaviours that might cause congestive heart failure or accelerate
progression.
The single most useful diagnostic test in the evaluation of patients is the comprehensive 2-dimensional
echocardiogram coupled with Doppler flow studies. Measurement of B-type natriuretic peptide can be useful
in the evaluation of patients at initial presentation.
Interventions that have a proven beneficial impact on patient survival include ACE inhibitors, angiotensin
receptor blockers, beta-blockers, aldosterone antagonists, hydralazine and nitrates, cardiac re-
synchronisation therapy, and implantable cardioverter defibrillators.
Definition
Heart failure is a condition in which the heart is unable to generate a cardiac output sufficient to meet the
demands of the body without increasing diastolic pressure. It can result from any cardiac disease that
compromises ventricular systolic or diastolic function or both. The term 'congestive heart failure' (CHF) is
reserved for patients with breathlessness and abnormal sodium and water retention resulting in oedema.
Heart failure comprises a wide range of clinical scenarios, from patients with normal left ventricular ejection
fraction (LVEF) >50% to those with reduced myocardial contractility (LVEF <40%).
Based on LVEF, heart failure is defined as follows:[1]
1. Heart failure with reduced ejection fraction (HFrEF): symptoms and signs with LVEF <40%.
2. Heart failure with mid-range ejection fraction (HFmrEF): symptoms and signs with LVEF 40% to 49%.
Other features include elevated natriuretic peptides (B-type natriuretic peptide [BNP] >35 nanograms/L
[>35 picograms/mL] or N-terminal pro-brain natriuretic peptide [NT-pro-BNP] >125 nanograms/L [>125
picograms/mL]) and at least one additional criterion: (a) relevant structural heart disease (e.g., left ventricular
hypertrophy [LVH] or left atrial enlargement), (b) diastolic dysfunction.
3. Heart failure with preserved ejection fraction (HFpEF): symptoms and signs with LVEF >50%. Other
features include elevated natriuretic peptides (BNP >35 nanograms/L [>35 picograms/mL] or NT-pro-BNP
>125 nanograms/L [>125 picograms/mL]) and at least one additional criteria: (a) relevant structural heart
disease (e.g., LVH or left atrial enlargement), (b) diastolic dysfunction. See our topic 'Heart failure with
preserved ejection fraction' for more information on this subtype.
This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Jun 16, 2021.
BMJ Best Practice topics are regularly updated and the most recent version of the topics
3
can be found on bestpractice.bmj.com . Use of this content is subject to our disclaimer (.
Use of this content is subject to our) . © BMJ Publishing Group Ltd 2021. All rights reserved.
Chronic congestive heart failure Theory
Epidemiology
Heart failure is a global disease. The prevalence of known heart failure in the developed world has been
estimated at 1% to 2%, and the incidence is thought to approach 1 to 9 per 1000 people per year.[4] The
THEORY
prevalence of heart failure is about 1.3% in China, 6.7% in Malaysia, 1.0% in Japan, 4.5% in Singapore,
0.12% to 0.44% in India, and 1.0% in South America.[5] In Australia, the prevalence of heart failure
is consistent with other developed countries at 1% to 2%; however, following age-standardisation, the
prevalence of heart failure is 1.7 times higher among Indigenous than non-Indigenous Australians.[6] In the
UK, heart failure is thought to account for a total of 1 million inpatient bed days and 5% of all emergency
admissions. These figures are projected to rise by as much as 50% in the next 25 years.[7]
The total prevalence of heart failure in the US is between 1.5% and 1.9%.[5] From 2013 to 2016, an
estimated 6.2 million adults aged ≥20 years had heart failure in the US.[8] In 2014 there were 1 million
new cases in patients aged >55 years.[8] Heart failure is the primary reason for 12 to 15 million clinic visits
and 6.5 million hospital-days each year.[9] [10] Recurrent hospitalisation is a major quality of life and cost
issue: for example, from 1990 to 1999, the annual number of hospitalisations increased from approximately
810,000 to over 1 million for primary diagnosis and from 2.4 million to 3.6 million for primary or secondary
diagnosis.[11] Patients are particularly prone to re-admission, with reported rates as high as 50% within 6
months of discharge.
Worldwide the absolute numbers of people living with heart failure are increasing.[4] The rising prevalence of
heart failure is not necessarily linked with an increase in heart failure incidence, as the incidence appears to
be stable or decreasing in some countries, in part due to better treatment and reduced mortality of patients
with acute myocardial infarctions earlier in life.[5] [4] Heart failure is primarily a condition of older people, and
thus the widely recognised 'ageing of the population' contributes to its increasing prevalence.[4]
The prevalence of heart failure increases with increasing age. In the US, among patients aged 40 to 59 years
the prevalence of heart failure is about 1.2% in males and 1.7% in females, whereas among patients aged
≥80 years the prevalence of heart failure is about 12.8% in males and 12% in females.[8] A major heart
study conducted in Australia in 2006 found that 6.3% of older residents (aged 60–86 years ) in Canberra had
overt symptomatic heart failure, and there was an even higher proportion of people with subclinical heart
failure.[12]
Aetiology
There are numerous and varied causes of heart failure.[1] [2]
Common causes of chronic heart failure include:
• Coronary artery disease

• Hypertension
• Valvular disease
• Myocarditis.
Other causes include:
• Infiltrative diseases: amyloidosis, haemochromatosis, sarcoid

• Congenital heart diseases
• Pericardial disease
4 This PDF of the BMJ Best Practice topic is based on the web version that was last updated: Jun 16, 2021.
• Toxin-induced: heroin, alcohol, cocaine, amfetamines, lead, arsenic, cobalt, phosphorus
• Infection: bacterial, fungal, viral (HIV), Borrelia burgdorferi (Lyme disease), parasite (e.g.,
Trypanosoma cruzi [Chagas disease])
• Endocrine disorders: diabetes mellitus, thyroid disease, hypoparathyroidism with hypocalcaemia,
THEORY
phaeochromocytoma, acromegaly, growth hormone deficiency
• Systemic collagen vascular diseases: lupus, rheumatoid arthritis, systemic sclerosis, polyarteritis
nodosa, hypersensitivity vasculitis, Takayasu syndrome, polymyositis, reactive arthritis
• Chemotherapy-induced: for example, adriamycin, trastuzumab
• Nutritional deficiencies: thiamine, protein, selenium, L-carnitine
• Pregnancy: peripartum cardiomyopathy
• Familial cardiomyopathy
• Tachycardia-induced cardiomyopathy
• Stress cardiomyopathy.
Although Chagas disease is an uncommon cause of congestive heart failure in Europe and North America, it
is an important cause of heart failure in Central and South America.[2] [4]
Some of these conditions tend to increase metabolic demand, which may not be matched by a sufficient
increase in cardiac output by the failing heart. Tachyarrhythmias also decrease the diastolic ventricular filling
time and increase myocardial oxygen demand. Uncontrolled hypertension depresses systolic function by
increasing the afterload against which the failing ventricle must pump blood, and may be the first clinical
manifestation. It should be emphasised that many of these causes may be completely reversible given
appropriate and timely treatment/intervention (e.g., revascularisation for stunned or hibernating myocardium;
standard therapy for peripartum or hypertensive cardiomyopathy; valvuloplasty or valve replacement for
valvular heart disease; standard treatment and adjunctive rate control therapy for tachycardia-induced
cardiomyopathy and cardiomyopathy related to sepsis and stress).[2] [13] [14] Other causes, such as scarred
myocardium or infiltrative cardiomyopathy, are currently considered irreversible.
Pathophysiology
The understanding of the pathophysiology of heart failure has evolved significantly over the last decades,
from the haemodynamic model to the neurohormonal paradigm.[15] Heart failure represents a complex
syndrome in which an initial myocardial insult results in the over-expression of multiple peptides with different
short- and long-term effects on the cardiovascular system. Neurohormonal activation is recognised to play a
pivotal role in the development as well as the progression of heart failure. In the acute phase, neurohormonal
activation seems to be beneficial in terms of maintaining adequate cardiac output and peripheral perfusion.
Sustained neurohormonal activation, however, eventually results in increased wall stress, dilation, and
ventricular remodelling, which contribute to disease progression in the failing myocardium, which eventually
leads to further neurohormonal activation. Left ventricular remodelling is the process by which mechanical,
neurohormonal, and possibly genetic factors alter ventricular size, shape, and function. Remodelling occurs
in several clinical conditions, including myocardial infarction, cardiomyopathy, hypertension, and valvular
heart disease; its hallmarks include hypertrophy, loss of myocytes, and increased interstitial fibrosis. One
potential deleterious outcome of remodelling, as the left ventricle dilates and the heart assumes a more
globular shape, is the development of mitral regurgitation. Mitral regurgitation results in an increasing volume
overload on the overburdened left ventricle that further contributes to remodelling and progression of disease
and symptoms.
5
Classification
American College of Cardiology/American Heart Association stages
of heart failure[2]
THEORY
This staged classification underscores the fact that established risk factors and structural abnormalities
are necessary for the development of heart failure, recognises its progressive nature, and superimposes
treatment strategies on the fundamentals of preventative efforts. Heart failure may progress from stage A to
stage D in a given patient, but generally does not follow the path in reverse.
• Stage A: patients at high risk of developing heart failure because of the presence of conditions that
are strongly associated with the development of heart failure (for example, hypertension, diabetes, or
coronary disease); however, such patients have no identified structural or functional abnormalities of
the pericardium, myocardium, or cardiac valves and have never shown signs or symptoms of heart
failure.
• Stage B: patients who have developed structural heart disease that is strongly associated with the
development of heart failure but who have never shown signs or symptoms of heart failure (for
example, asymptomatic post-infarction left ventricular dysfunction).
• Stage C: patients who have current or prior symptoms of heart failure associated with underlying
structural heart disease.
• Stage D: patients with advanced structural heart disease and marked symptoms of heart failure at
rest despite maximal medical therapy and who require specialised interventions (for example, heart
transplant or left ventricular assist devices).
Framingham criteria for the diagnosis of CHF[3]

Heart failure is essentially a clinical diagnosis. Clinical criteria for diagnosing heart failure, the Framingham
criteria for the diagnosis of CHF, were established before the widespread use of echocardiographic
assessment of systolic and diastolic dysfunction. The Framingham clinical criteria, listed below, have been
extremely useful for identifying heart failure patients, both in clinical practice and in epidemiological studies,
for more than 40 years. However, because their specificity is greater than their sensitivity, it is recognised
that they probably miss mild cases of heart failure. In order to come up with a definite diagnosis of CHF, one
needs to have either 2 major criteria or the combination of 1 major and 2 minor criteria.
Major criteria:
• Neck vein distension

• Rales
• Acute pulmonary oedema
• S3 gallop
• Increased venous pressure >16 cm of water
• Circulation time >25 seconds
• Hepatojugular reflux
• Cardiomegaly
• Paroxysmal nocturnal dyspnoea or orthopnoea.
Minor criteria:
• Ankle oedema
• Night cough
• Dyspnoea on exertion
• Hepatomegaly
• Pleural effusion
THEORY
• Less than one third maximum vital capacity
• Tachycardia (heart rate >120 bpm).
Major or minor criteria:
• Weight loss greater than 4.5 kg in 5 days in response to treatment.
Case history
Case history #1
A 67-year-old woman presents to her primary care physician complaining of increasing shortness
of breath, especially when trying to sleep. She has a history of poorly controlled hypertension and
hyperlipidaemia, and is being treated with a beta-blocker and statin therapy. She does not smoke and
drinks alcohol in moderation. On examination, her blood pressure is 160/90 mmHg and heart rate is
126 beats per minute. There is an audible S4 and the jugular venous pressure is elevated 3 cm above
normal. There is no oedema, but she has fine bilateral mid to lower zone crepitation on lung examination.
The ECG shows left ventricular hypertrophy and a transthoracic echocardiogram shows left ventricular
hypertrophy, left atrial dilatation, normal left and right ventricular systolic function, with a left ventricular
ejection fraction of 60%.
Case history #2
A 60-year-old man presents to the accident and emergency department. He reports being progressively
short of breath. He has a history of hypertension, non-insulin-dependent diabetes mellitus, and has
been a heavy smoker for more than 40 years. He underwent a successful primary angioplasty for a large
acute anterior myocardial infarction 2 months ago. His blood pressure is 75/40 mmHg, his heart rate 110
beats per minute, and his respiratory rate 30. He has elevated neck veins and a prominent S3. His ECG
shows sinus tachycardia, and a transthoracic echocardiogram performed in the A&E department reveals
impaired left ventricular systolic function, with an ejection fraction of 20%.
Other presentations
Many patients remain asymptomatic for an extended period of time because mild impairment in
cardiac function is balanced by compensatory mechanisms. Often, clinical manifestations occur only
in the presence of precipitating factors that increase the cardiac workload and tip the balanced state
into one of decompensation. Thus, the first symptoms and signs may be those of the underlying
precipitating condition, such as atrial flutter or fibrillation, anaemia, fever, infection, hyperthyroidism, or
even pregnancy. A large pulmonary embolism can also lead to the first presentation of symptoms, or
to exacerbation of known chronic CHF, by causing hypoxaemia, decreased myocardial oxygen supply,
and increased right ventricular afterload. An acute ischaemic insult (i.e., an acute coronary syndrome
or an myocardial infarction) or the initiation of a negative inotropic medicine for another reason (e.g.,
7
large doses of beta-blockers and certain calcium channel blockers for hypertension) can acutely depress
myocardial contractility and precipitate symptoms in an otherwise compensated patient.
THEORY
Chronic congestive heart failure Diagnosis
Approach
Heart failure is primarily a condition of older people and has a higher prevalence in men at all ages.[4] [8]
[79]
Identification of the condition responsible for the cardiac structural and/or functional abnormalities may be
important, because some conditions that lead to left ventricular dysfunction are potentially treatable and/
or reversible.[2] Efforts to identify a cause frequently allow the detection of co-existent conditions that may
contribute to or exacerbate the severity of symptoms. However, it may not be possible to discern the cause of
heart failure in many patients presenting with this syndrome, and in others, the underlying condition may not
be amenable to treatment.
A number of precipitating factors may lead to impaired cardiac function, potentially leading to an episode
of acute heart failure. Detection and treatment of precipitating factors plays an important role in patient
management. Precipitating factors include excessive salt intake, lack of adherence (with respect to
medication and diet), myocardial infarction, pulmonary embolism, uncontrolled hypertension, cardiac
arrhythmias, infection, hypothyroidism, hyperthyroidism, renal dysfunction, and alcohol and drug abuse.[1]
Patient history
The complexity and variety of potential causative factors means that a multitude of patient historical
factors may be relevant. A history of hypertension; diabetes mellitus; dyslipidaemia; tobacco use;
coronary, valvular, or peripheral vascular disease; rheumatic fever; heart murmur or congenital heart
disease; personal or family history of myopathy; mediastinal irradiation; and sleep-disturbed breathing
should be enquired about. The drug history should record the past or current use of illicit drugs; alcohol;
ephedra; or antineoplastic agents such as anthracyclines, trastuzumab, or high-dose cyclophosphamide,
because heart failure may occur years after exposure to doxorubicin or cyclophosphamide. The history
and physical evaluation should include specific consideration of non-cardiac diseases such as collagen
vascular disease, bacterial or parasitic infection, obesity, thyroid excess or deficiency, amyloidosis, and
phaeochromocytoma.
DIAGNOSIS
A detailed family history should be obtained, not only to determine whether there is a familial pre-
disposition to atherosclerotic disease but also to identify relatives with cardiomyopathy, sudden
unexplained death, conduction system disease, and skeletal myopathies.
Dyspnoea on exertion or at rest is the most common symptom of left-sided heart failure. With increasing
failure patient may develop leg oedema and abdominal distension due to ascites.
Physical examination
Particular attention should be paid to the cardinal signs of heart failure. Their presence (and degree) may
depend on severity of heart failure and associated comorbid disease.
General examination may reveal tachycardia and cyanosis. A focused cardiovascular examination may
reveal elevated jugular venous pressure, ankle oedema, and a displaced apex beat, which suggests
cardiomegaly. On auscultation, besides presence of pulmonary rales or crepitation, an S3 gallop may be
present, which has prognostic significance.
Clinical manifestations of the underlying aetiology of heart failure may be present, for example,
macroglossia and neuropathy may point to infiltrative cardiomyopathy like amyloidosis; pallor (which may
reflect anaemia); irregularly irregular pulse (reflecting atrial fibrillation); systolic murmur of aortic stenosis
9
and mid diastolic murmur of mitral stenosis; or overt signs of thyrotoxicosis. In patients on dialysis, a
large arteriovenous fistula may occasionally be the precipitating factor. However, further discussion of the
clinical features of aetiologic(al) pathways is beyond the scope of this topic.
Investigations
For all patients, initial investigations should include ECG, chest x-ray, transthoracic echocardiogram,
and baseline haematology and blood chemistry, including full blood count, serum electrolytes (including
calcium and magnesium), serum urea and creatinine, liver function tests, and B-type natriuretic peptide/
N-terminal pro-brain natriuretic peptide levels. Anaemia and high lymphocyte percentage are strong risk
factors and prognostic markers of poor survival. In patients presenting with dyspnoea, measurement of
natriuretic peptide biomarkers is useful to support a diagnosis or exclude heart failure. However, elevated
plasma levels of natriuretic peptides can occur with a wide variety of cardiac and non-cardiac causes;
therefore, clinical judgement is necessary.[80]
Blood glucose, thyroid function tests and blood lipids are useful to assess for commonly associated
comorbid disease.
Subsequent investigations that help in assessing severity of heart failure and functional status
include non-invasive stress imaging (cardiovascular MRI, stress echocardiogram, SPECT, PET),
standard exercise stress testing (bicycle or treadmill), coronary angiogram, cardiac CT angiography,
cardiopulmonary exercise testing with VO₂ max, 6-minute walking test exercise, left and right heart
catheterisation, and endomyocardial biopsy. Troponin measurement is helpful in further risk stratification
in chronic heart failure, as an elevated level is associated with progressive left ventricular dysfunction and
increased mortality.[2] [81] Soluble ST2 and galectin-3 (biomarkers for myocardial fibrosis) are predictive
of death and hospitalisation in patients with heart failure and are additive to natriuretic peptide in their
prognostic value.[2]
Based on clinical history, HIV screening and measurement of iron levels and fasting transferrin saturation
to screen for haemochromatosis may also be performed. A cardiac MRI scan is particularly useful in
the investigation of myocarditis and infiltrative cardiomyopathy. Multi-slice CT (MSCT) can be used for
DIAGNOSIS
left ventricular ejection fraction (LVEF) estimation. There appears to be no significant difference in LVEF
estimation between MSCT and MRI, and also between MSCT and transthoracic echocardiogram.[82]
MSCT may offer additional benefit as it provides a combined evaluation of LVEF and coronary artery
disease.
History and exam

Key diagnostic factors
presence of risk factors (common)
• Key risk factors include: history of myocardial infarction; diabetes mellitus; dyslipidaemia; old age;
male sex; hypertension; left ventricular dysfunction; exposure to cardiotoxic agents; left ventricular
hypertrophy; renal insufficiency; valvular heart disease; sleep apnoea; cocaine abuse; and family
history of heart failure.
dyspnoea (common)
• The most common symptom of left-sided heart failure. May occur with exertion (New York Heart
Association [NYHA] II-III) or, in more severe cases, at rest (NYHA IV). This is considered a minor
criterion for the diagnosis of heart failure (Framingham criteria).
neck vein distension (common)

• A major Framingham criterion for the diagnosis of heart failure.
S3 gallop (common)
cardiomegaly (common)
• Cardiomegaly is a major Framingham criterion for the diagnosis of heart failure. Left ventricular dilation
or hypertrophy are common findings.
hepatojugular reflux (common)

rales (common)
orthopnoea and parox ysmal nocturnal dyspnoea (uncommon)

• Orthopnoea (dyspnoea that develops in the recumbent position) usually worsens immediately after
lying down, because of a sudden increase in venous return (i.e., pre-load). Paroxysmal nocturnal
dyspnoea occurs several hours after the patient lies down to sleep; it results from the central re-
distribution of extravascular fluid that progressively increases the venous return.
nocturia (uncommon)
• Increased frequency of uresis occurs several hours after the patient lies down to sleep; it also results
from the central re-distribution of extravascular fluid that augments the amount of circulating blood
cleared from the kidneys.
DIAGNOSIS
Other diagnostic factors
tachycardia (heart rate >120 beats per minute) (common)
• A minor Framingham criterion for the diagnosis of heart failure.
chest discomfort (common)

• A symptom of poor coronary perfusion.
hepatomegaly (common)
• A minor Framingham criterion for the diagnosis of heart failure; may cause abdominal discomfort/
distension and nausea.
ankle oedema (common)

night cough (common)

11
signs of pleural effusion (common)
fatigue, muscle weakness, or tiredness (common)

• Symptom of poor tissue (muscle) perfusion.
palpitations, pre-syncope, or syncope (uncommon)

• This may be the result of frequent ectopic supraventricular or ventricular beats or may reflect
paroxysms of atrial flutter/fibrillation; permanent atrial fibrillation may or may not cause palpitations.
Syncope may result from fast atrial arrhythmias or ventricular tachycardia.
lethargy/confusion (uncommon)
• Symptom of poor tissue (brain) perfusion.
Risk factors
Strong
myocardial infarction (MI)
• The link between MI and risk of heart failure development is strongly and consistently supported by the
literature. MI is a potent risk factor for developing heart failure.[16] [17] [18] [19] [20] [21]
hypertension
• Hypertension has consistently been linked to an increased risk of heart failure in the literature and
confers a 2- to 3-fold increase in risk of developing heart failure.[16] [17] [18] [19] [20] [21] [22]
Elevated systolic blood pressure, elevated diastolic blood pressure, and elevated pulse pressure
have all been associated with increased risk for heart failure.[23] [24] Among the Framingham cohort,
a 1 standard deviation (20 mmHg) increase in systolic blood pressure was associated with a 56%
increased risk for heart failure, a 1 standard deviation (10 mmHg) increase in diastolic blood pressure
DIAGNOSIS
was associated with 24% increased risk, and a 1 standard deviation (16 mmHg) increase in pulse
pressure was associated with a 55% increase in risk.[23]
diabetes mellitus
• Diabetes mellitus has been associated with a 3- to 5-fold increase in the risk of developing heart
failure,[17] [18] [19] [21] [25] [26] with the highest increase in relative risk found among women[17]
[21] and people with asymptomatic left ventricular dysfunction.[25] Even a slight increase of 1% in
haemoglobin A1C has been linked to a greater than 10% risk of hospitalisation for heart failure or
death.[27]
dyslipidaemia
• Lipid abnormalities have been linked to increased risk for heart failure.[28] [29] [30] Compared with
men with ratios of total cholesterol:HDL cholesterol of less than 5, in one study men with ratios of 5
to 9.9 had a 1.5-times greater incidence of heart failure, and men with ratios of greater than 10 had a
nearly 5-times greater incidence of heart failure.[28] In the same study, women with ratios greater than
10 had more than 6-times greater incidence of heart failure than women with ratios less than 5.[28]
In one clinical trial of patients with coronary artery disease, lipid lowering was associated with a 21%
reduction in the risk of developing heart failure.[31]
old age
• Increasing age has been consistently linked to a higher risk of developing heart failure.[3] [16] [17]
[18] [19] [20] [32] In the Framingham cohort, the incidence of heart failure increased steadily with
increasing age.[17] In a cohort of people over age 65 years, every 5-year incremental increase in age
was associated with a hazard ratio of 1.37.[19] In another study, the incidence rate of heart failure
among the oldest people (age >80 years) was double that of the youngest people (age 65 to 69
years).[32]
male
• Male sex has been consistently linked to a higher risk of developing heart failure.[3] [16] [17] [18]
[19] [20] [21] [32] In the Framingham cohort, women had a one third lower incidence of heart failure
than men, and male sex was associated with a hazard ratio of 1.34.[17] [19] [21] In other studies the
incidence among males is 2 to 4 times that of females.[16] [32] In the National Health and Nutrition
Examination Survey (NHANES I) study, which followed a cohort of 13,643 people for an average of 19
years, being male was associated with a relative risk of heart failure of 1.24.[33]
obesity
• Excess body weight is now an established risk factor for the development of heart failure. Among a
subset of the Framingham cohort, the risk of heart failure increased by 5% for men and 7% for women
with each increase of 1 in body mass index; obese subjects (body mass index 30 or above) had a risk
of heart failure double that of non-obese subjects.[34] Obesity may result in heart failure by inducing
haemodynamic and myocardial changes that lead to cardiac dysfunction, or may predispose to heart
failure risk factors (e.g., hypertension, obstructive sleep apnoea) and other cardiovascular disease risk
factors (e.g., diabetes, dyslipidaemia).[35]
exposure to cardiotoxic agents

• Doxorubicin and cyclophosphamide can cause myocardial damage leading to left ventricular
DIAGNOSIS
dysfunction and heart failure.[43] [44] These chemotherapeutic agents increase risk for heart failure
both during acute treatment and for several months after treatment has ended, with increasing risk
with increasing cumulative dose.[45] [46] In addition, trastuzumab, a recombinant DNA-derived
humanised monoclonal antibody used widely in the treatment of breast cancer, is also associated with
the development of cardiomyopathy. The antihypertensive medicine doxazosin has been linked to an
increased risk of heart failure. Thiazolidinediones (a class of drug used for the treatment of diabetes)
have been associated with an increased risk of heart failure.
• Mediastinal irradiation can cause direct myocardial damage leading to left ventricular dysfunction and
heart failure both during acute treatment and for several years after treatment has ended.
left ventricular dysfunction

• Moderate-to-severe asymptomatic left ventricular dysfunction (ejection fraction [EF] <40%) has
been associated with a hazard ratio of heart failure of 7.8, while mild asymptomatic left ventricular
dysfunction (EF 40% to 50%) has been associated with a hazard ratio of 3.3.[47]
left ventricular hypertrophy

• Left ventricular hypertrophy, such as in hypertrophic obstructive cardiomyopathy, on ECG has been
associated with a higher risk of heart failure, with highest relative risk among younger people.[48]
13
renal insufficiency
• Renal insufficiency, defined by elevated serum creatinine (over 133 micromols/L [1.5 mg/dL] in men
and 115 micromols/L [1.3 mg/dL] in women) or reduced creatinine clearance less than 1 mL/s/m²
(60 mL/minute), has been linked to increased risk for development of heart failure. Compared with
subjects with creatinine of less than 97 micromols/L (<1.1 mg/dL), subjects with creatinine of 115
to 132 micromols/L (1.3 to 1.49 mg/dL) had almost double the risk of developing CHF, subjects with
creatinine of 133 to 149 micromols/L (1.5 to 1.69 mg/dL) had almost triple the risk, and those with
creatinine above 150 micromols/L (>1.7 mg/dL) had almost quadruple the risk.[49] [50]
valvular heart disease

• Cardiac valvular abnormality was associated with an odds ratio of heart disease of 2.43 among men
and 3.47 among women in a multi-variate profile based on the Framingham cohort.[51] Valvular
abnormalities create pressure overload (e.g., aortic stenosis, mitral stenosis) or volume overload
(e.g., mitral regurgitation), which are initially compensated for by mechanisms such as ventricular
hypertrophy or ventricular dilation.[52] Ventricular remodelling alters cardiac contractility and increases
the risk of heart failure.
sleep apnoea
• Sleep-disordered breathing has been linked with increased risk of heart failure in multiple studies.[53]
[54] [55]
elevated homocysteine
• In the Framingham cohort, elevated plasma homocysteine levels were linked with a roughly three
quarter increased risk for developing heart failure.[59]
cocaine abuse
• Cocaine abuse has been strongly associated with the development of heart failure.[60] [61] [62]
family history of heart failure

DIAGNOSIS
• Several polymorphisms have been linked with an increased risk of developing heart failure: for
example, a deletion of 4 amino acids in position 322 to 325 of the gene coding for a2C-adrenergic
receptors (a2C Del322-325) in sympathetic nerve endings in the heart has been studied as a possible
link to the development of heart failure. A second polymorphism that was evaluated as a candidate
for developing heart failure is a change in position 389 of the gene for beta1-adrenergic receptors
(b1Arg389) on myocytes. In the same study, patients who were homozygous for this deletion had a 10-
fold increase in risk of developing heart failure.[63]
atrial fibrillation
• Atrial fibrillation increases the risk of thrombo-embolic events (e.g., stroke) and may lead to a
worsening of symptoms. Atrial fibrillation may also serve as a predictor of mortality, or lead to
tachycardiomyopathy, though evidence is less clear.[1]
thyroid disorders
• For example, thyrotoxicosis and hypothyroidism. Thyroid disorders are treatable, but are linked to sinus
tachycardia, bradycardia, and atrial tachycardia/flutter/fibrillation.[1]
anaemia
• Anaemia is a strong risk factor and prognostic marker of poor survival. A high prevalence of
iron deficiency has been reported in heart failure.[64] Iron deficiency in heart failure is due to
gastrointestinal or genitourinary blood loss related to the use of antiplatelet drugs and/or oral
anticoagulation, impaired nutrition, malabsorption, and reduced intracellular uptake of iron.[65] [66]
elevated tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6)

• TNF-alpha is a pro-inflammatory cytokine associated with myocyte death and cardiac dysfunction.[67]
IL-6 is a similar pro-inflammatory cytokine.[68]
elevated C-reactive protein (CRP)

• Among the Framingham cohort, an increase of 48 nanomols/L (5 mg/dL) in CRP level was associated
with over a 2-fold increase in risk of heart failure.[68] People who also had elevated serum IL-6 and
TNF-alpha values had a 4-fold increase in risk of heart failure.[68]
decreased insulin-like growth factor-1 (IGF-1)

• IGF-1 has been shown to have positive inotropic effects and to decrease the rate of cellular
apoptosis.[69] [70] IGF-1 has also been tentatively linked to vasodilation, which may improve cardiac
emptying.[71] Among the Framingham cohort, patients with a serum IGF-1 level below 18 nanomols/L
(140 mg/L) had double the risk of developing heart failure.[72]
elevated natriuretic peptides

• In the Framingham cohort, increased levels of plasma B-type natriuretic peptide (BNP) and N-terminus
of the atrial natriuretic peptide pro-hormone (N-ANP) were associated with an increased risk of heart
failure. BNP levels above the 80th percentile (20 nanograms/L [20 picograms/mL] for men and 23.3
nanograms/L [23.3 picograms/mL] for women) were associated with a 3-fold increase in heart failure
risk.[73]
dilation of the left ventricle
DIAGNOSIS
• The risk-factor-adjusted hazard ratio for heart failure in an asymptomatic population was 1.47 per 1
standard deviation increase in left ventricular end-diastolic diameter and 1.43 per 1 standard deviation
increase in left ventricular end-systolic dimension.[47]
increased left ventricular mass

• In one cohort, those who developed heart failure had an initial average left ventricular mass/height of
106 g/m versus 88 g/m among those who did not develop heart failure.[47] [74] [75]
abnormal left ventricular diastolic filling

• Alternations in the E to A wave ratio, both low and high, have been associated with heart failure risk,
with those with the lowest E to A wave ratio (<0.7) having a relative risk of 1.88 and those with the
highest E to A wave ratio (>1.5) having a relative risk of 3.50.[47] [75]
Weak
15
low socio-economic status
• The National Health and Nutrition Examination Survey (NHANES I) study found that low socio-
economic status (as indicated by less than high school education) was associated with a relative risk
of heart failure of 1.22 (population attributable risk 8.9%).[33]
tobacco consumption
• In contrast to the strong influence of cocaine abuse on the development of heart failure, the literature
on the importance of smoking independent of other factors is conflicting.[17] [33] [36] [37] In the
Framingham cohort, cigarette smoking was not linked with increased incidence of heart failure except
among men over age 64 years.[17] In other studies, tobacco use has been associated with a relative
risk of heart failure of 1.59 and of 1.51 (smoking <15 cigarettes a day) to 2.31 (smoking 15 or more
cigarettes a day).[33] [36]
excess alcohol consumption

• Current data strongly support a relationship between excess alcohol consumption and the
development of heart failure.[38] [39] [40] This may be related to both direct myocardial toxicity of
alcohol and the higher risk of hypertension development. However, the data also suggest a possible
weakly protective effect of moderate alcohol consumption.[41] This may be related to lower risk of
diabetes and myocardial infarction, and favourable changes in the lipid profile, platelet function, and
blood clotting associated with moderate alcohol intake.
excess sodium intake

• The National Health and Nutrition Examination Survey (NHANES) found the relative risk for a 100-
mmols/day increase in sodium intake was 1.26.[42]
excess coffee consumption

• Consumption of 5 or more cups of coffee a day has been associated with a relative risk of heart failure
of 1.11.[36]
tachycardia
DIAGNOSIS
• Tachycardia-induced cardiomyopathy has been well described in the literature. Among the
Framingham cohort, an increase in heart rate of 10 beats per minute was linked with a greater than
10% increased risk of developing heart failure.[51]
depression/stress
• Risk is double among depressed compared with non-depressed older people.[56] [57]
microalbuminuria
• Although no link between microalbuminuria and the development of heart failure has been established,
microalbuminuria was linked with a 3-fold increased risk of heart failure hospitalisation in the Heart
Outcomes Prevention Evaluation study.[58]
Investigations
1st test to order
Test Result
transthoracic echocardiogram systolic heart failure:
depressed and dilated
• Allows for the accurate determination of biventricular systolic
left and/or right ventricle
and diastolic function. With systolic heart failure, echo usually
with low ejection fraction;
demonstrates a dilated left and/or right ventricle with low ejection
fraction. With pure diastolic heart failure left ventricular ejection diastolic heart failure:
LVEF normal but LVH and
fraction (LVEF) is normal but there is evidence of left ventricular
abnormal diastolic filling
hypertrophy (LVH) and of abnormal diastolic filling patterns on
pat terns
Doppler evaluation. Echocardiogram can also identify valvular,
myocardial, or pericardial disease or may reveal evidence of
underlying coronary artery disease (regional wall motion/thickness
abnormalities). A hypertrophied heart may be due to hypertension,
hypertrophic obstructive cardiomyopathy, or infiltrative disease like
amyloidosis. It should be performed in every patient presenting with
heart failure symptoms.
ECG evidence of underlying
coronary artery
• QRS duration above 120 ms should always raise the question of
disease, left ventricular
ventricular dyssynchrony.
hypertrophy, or atrial
enlargement; may be
conduction abnormalities
and abnormal QRS
duration
CXR abnormal
• May reveal pulmonary vascular congestion (vascular redistribution,
Kerley B lines), cardiomegaly (increased cardiothoracic ratio), or
pleural effusion (usually right-sided but often bilateral).
B-type natriuretic peptide (BNP)/N-terminal pro-brain natriuretic elevated
DIAGNOSIS
peptide (NT-pro-BNP) levels
• Elevated plasma BNP levels have been associated with reduced left
ventricular ejection fraction,[83] left ventricular hypertrophy, elevated
left ventricular filling pressures, and acute myocardial infarction
and ischaemia, although they can occur in other settings, such as
pulmonary embolism and chronic obstructive pulmonary disease.[83]
[84] [85] They are sensitive to other biological factors, such as age,
sex, weight, and renal function. Elevated levels lend support to
a diagnosis of abnormal ventricular function or haemodynamics
causing symptomatic heart failure.[86] [87] [88] A low plasma BNP
level (<100 nanograms/L or <100 picograms/mL) can rapidly rule
out decompensated heart failure and point to a pulmonary cause. A
high plasma BNP level (>400 nanograms/L or >400 picograms/mL)
strongly supports the diagnosis of abnormal ventricular function (i.e.,
heart failure). Intermediate values (100 to 400 nanograms/L or 100
to 400 picograms/mL) fall into the so-called 'grey zone' and should
spur a search for a potential non-cardiac cause of dyspnoea: for
example, COPD. In patients presenting with dyspnoea, measurement
of natriuretic peptide biomarkers is useful to support a diagnosis or
exclude heart failure. However, elevated plasma levels of natriuretic
17
Test Result
peptides can occur with a wide variety of cardiac and non-cardiac
causes; therefore, clinical judgement is necessary.[80]
• Trials with this diagnostic marker suggest that its use may reduce
both the time to hospital discharge and the cost of treatment.[89]
[90] [91] BNP levels tend to be less elevated in heart failure with
preserved ejection fraction than in heart failure with low ejection
fraction and are lower in obese patients.[92] Levels of BNP may
be elevated meaningfully in women and in people over 60 years of
age who do not have heart failure, and thus BNP levels should be
interpreted cautiously in such individuals.[73] [93] [94]
FBC laboratory testing may
• Anaemia and high lymphocyte percentage are strong risk factors and reveal important heart
failure aetiologies, the
prognostic markers of poor survival.
presence of disorders
or conditions that can
lead to or exacerbate
heart failure; laboratory
testing could also reveal
important modulators of
therapy
serum electrolytes (including calcium and magnesium) decreased sodium

(usually <135 millimols/L),
• Baseline electrolytes should be obtained in all patients.
altered potassium
serum creatinine, blood urea nitrogen normal to elevated

• Reflects tissue perfusion, fluid status, rules out renal disease.
blood glucose elevated in diabetes
• Screening for diabetes mellitus as a comorbid condition. Diabetes
mellitus has been associated with a 3- to 5-fold increase in the risk of
developing heart failure.[17] [18] [19] [21] [25] [26]
LFT normal to elevated
DIAGNOSIS
• Reflects abdominal congestion.

thyroid function tests (especially thyroid-stimulating hormone primary hypothyroidism:
[TSH]) elevated TSH, decreased
free thyroxine (FT4);
• Screening for hypo- or hyperthyroidism. Both can be a primary or
hyperthyroidism:
contributory cause of heart failure.
decreased TSH, elevated
free triiodothyronine,
elevated FT4
blood lipids elevated in dyslipidaemia,

decreased in end-stage
• Screening for dyslipoproteinaemias/metabolic syndrome.
heart failure, especially
in the presence of cardiac
cachexia
serum ferritin elevated (normal value

22-449 picomol/L [10-200
• For evaluation of cardiomyopathy due to iron overload
nanograms/mL])
cardiomyopathy/haemochromatosis.
transferrin saturation elevated level of
transferrin saturation;
• For evaluation of cardiomyopathy due to iron overload
complete or almost
cardiomyopathy/haemochromatosis.
Test Result
complete transferrin
saturation (normal
transferrin saturation 22%
to 46%)
DIAGNOSIS
19
Other tests to consider
Test Result
non-invasive stress imaging (cardiovascular MRI, stress ischaemia, scar, viable
echocardiogram, SPECT, PET) myocardium
• To detect myocardial ischaemia and viability when underlying
ischaemic heart disease is suspected.
standard exercise stress testing (bicycle or treadmill) usually reduced exercise
• Provides an objective assessment of the patient's functional exercise capacity in idiopathic
dilated cardiomyopathy;
limitation and haemodynamic response to exercise. Test is ordered
reduced exercise
when exercise-induced arrhythmias or ischaemia are suspected.
Caution should be taken if there is a high likelihood for aortic stenosis capacity and signs of
impaired myocardial
or hypertrophic obstructive cardiomyopathy.
perfusion in ischaemic
cardiomyopathy; however,
functional capacity may
be completely normal
in patients with low
left ventricular systolic
function
coronary angiogram coronary artery disease/

stenosis
• Provides assessment of coronary stenosis, and is particularly
indicated in patients with heart failure and angina, ventricular
tachycardia, or cardiac arrest. It is also done in patients with heart
failure and ischaemia on non-invasive stress test.
cardiac CT angiography coronary artery disease/
stenosis
• Its main use is in patients with heart failure who have low or
intermediate pre-test probability of underlying coronary artery
disease, or those with equivocal non-invasive stress tests.
• In clinical practice it is also useful in patients with a clinical picture
of stress/Takotsubo cardiomyopathy, in whom significant proximal
coronary artery disease needs to be excluded as a cause of
DIAGNOSIS
underlying presentation and echocardiogram findings.

cardiopulmonary exercise testing with VO₂ max reduced VO₂ max
• Provides the most objective assessment of the patient's functional
status.
6-minute walking test exercise as an alternative to
cardiopulmonary exercise
• A patient with heart failure who cannot walk more than 300 m in 6
minutes has a substantially greater annual risk of death than one who testing it may provide an
objective assessment of
can walk 450 m or more.
the patient's functional
status
right heart catheterisation provides objective

haemodynamic
• Considered in patients intolerant to standard medical therapy, in
assessment of left
whom medical therapy has failed to achieve symptomatic relief,
ventricular filling
before initiation of IV inotrope or inodilator therapy and in candidates
pressure and direct
for heart transplantation.
measures of cardiac
output and pulmonary
and systemic resistance
Test Result
endomyocardial biopsy rarely necessary to
establish the aetiology
• Ordered if acute myocarditis (giant cell or eosinophilic) or primary
of heart failure; provides
infiltrative diseases of the heart (amyloidosis, active cardiac
definitive pathological
sarcoidosis) suspected.
evidence of cardiac and
systemic disease
serum HIV enzyme-linked immunosorbent assay positive or negative

• The majority of patients who have cardiomyopathy due to HIV do not
present with symptoms of heart failure until other clinical signs of HIV
infection are apparent.
cardiac MRI myocarditis: sub-
epicardial delayed
• Particularly useful in evaluation of conditions like myocarditis,
enhancement in
constrictive pericarditis, and infiltrative cardiomyopathy.
myocardium, high
signal in myocardium
in T2-weighted
imaging; infiltrative
cardiomyopathy:
amyloid (global sub-
endocardial delayed
enhancement); sarcoid:
(delayed enhancement);
no sub-endocardial
delayed enhancement;
constrictive pericarditis:
thick pericardium as well
as diastolic septal bounce
with inspiration
biomarkers borderline to minimally

elevated
• Troponin is helpful in further risk stratification in chronic heart failure,
as elevated level is associated with progressive left ventricular
DIAGNOSIS
dysfunction and increased mortality.[2] [81]
• Soluble ST2 and galectin-3 (biomarkers for myocardial fibrosis) are
predictive of death and hospitalisation in patients with heart failure
and are additive to natriuretic peptide in their prognostic value.[2]
multi-slice computed tomography (MSCT) quantifies LVEF and
coronary artery disease
• A method for left ventricular ejection fraction (LVEF) estimation.
There appears to be no significant difference in LVEF estimation
between MSCT and MRI, and also between MSCT and transthoracic
echocardiogram.[95]
• May offer additional benefit as it provides a combined evaluation of
LVEF and coronary artery disease.
21
Differentials
Condition Differentiating signs / Differentiating tests

symptoms
Ageing/physical inactivity • Ageing, deconditioning, • Elucidation of the precise
and/or obesity may cause a reason for exercise
reduction in effort tolerance intolerance can be difficult
due to dyspnoea and/or because several disorders
fatigue, but without the may co-exist in the same
additional major and minor patient. Echocardiography
criteria for diagnosing heart in heart failure shows
failure. characteristic signs of heart
failure. However, a clear
distinction can sometimes be
made only by measurements
of gas exchange or blood
oxygen saturation or by
invasive haemodynamic
measurements during
graded levels of exercise
(i.e., cardiopulmonary
exercise test with VO₂ max).
COPD/pulmonary fibrosis • Dyspnoea may be episodic, • Pulmonary function tests

with or without environmental will give definite diagnosis of
triggers, and is usually an obstructive or restrictive
accompanied by cough, pulmonary disease. Plasma
wheezing, sputum, and B-type natriuretic peptide
a history of smoking or levels may be intermediate
industrial exposure. (100 to 400 nanograms/L or
100 to 400 picograms/mL) in
COPD.
Pneumonia • Patients may present with • CXR may show signs of

DIAGNOSIS
fever, cough, and productive consolidation. FBC may

sputum, with focal signs of show elevated WBC, and
consolidation (increased blood cultures may be
vocal fremitus and bronchial positive for the aetiological
breathing). organism.
Pulmonary embolism (PE) • Sudden onset of chest pain, • ECG is abnormal in the
dyspnoea, and haemoptysis, majority of patients with PE
especially after childbirth, and may show a deep S
are suggestive of PE.[96] wave in lead I and a deep Q
Dyspnoea with or without wave and T-wave inversion
chest pain may be present in in lead III (S1-Q3-T3). Other
other conditions associated common changes include
with venous thrombosis and sinus tachycardia, complete
PE (e.g., cancer, prolonged or incomplete right bundle-
immobilisation, postoperative branch block, and T-wave
state). inversion in the inferior (II,
III, aVF) or the anterior leads
(V1 to V4).
• Normal levels of D-dimers
can help to exclude PE,
but elevated levels occur in

symptoms
other conditions (e.g., aortic
dissection and many types of
cardiomyopathies) as well as
in PE.
Post-partum • Patients most commonly • In the presence of raised

cardiomyopathy (PPCM) present with dyspnoea, but D-dimers (commonplace in
other frequent complaints pregnancy) and positive risk
include cough, orthopnoea, factors for thromboembolic
paroxysmal nocturnal events, echocardiography
dyspnoea, haemoptysis, will identify the underlying
and chest discomfort, left ventricular systolic
which are also common dysfunction and point to
symptoms of pulmonary the diagnosis of PPCM. It
embolism.[96] PPCM is usually shows left ventricular
defined on the basis of 4 enlargement and significant
criteria: 1) development of global reduction in ejection
cardiac failure in the last fraction. Other findings
month of pregnancy or within may include left atrial
5 months of delivery; 2) enlargement, mitral and
absence of an identifiable tricuspid regurgitation, and a
cause for the cardiac failure; small pericardial effusion.
3) absence of recognisable
heart disease before the
last month of pregnancy;
4) left ventricular systolic
dysfunction shown on
echocardiograph. A number
of potential risk factors may
point to the diagnosis of
PPCM, including age >30
years, multiparity, women of
African descent, pregnancy
DIAGNOSIS
with multiple fetuses, a
history of pre-eclampsia/
eclampsia/post-partum
hypertension, and maternal
cocaine misuse.
Cirrhosis • Typically causes jaundice, • LFTs are abnormal.

fatigue, nausea, peripheral Ultrasound or CT scan may
oedema, ascites, bruising detect ascites and liver
and prolonged bleeding, abnormalities. Liver biopsy
gynaecomastia, and shows characteristic cirrhotic
haematemesis. changes and may reveal the
underlying cause.
Nephrotic syndrome • Typically causes peripheral • Urinalysis shows proteinuria,

oedema, fatigue, dyspnoea, and serum albumin is
and loss of appetite. reduced. Twenty-four-hour
urine collection shows >3.5
g protein. Serum urea and
creatinine clearance may
be abnormal in later stages.
Serum cholesterol and
triglyceride levels may be
23

symptoms
raised. Kidney ultrasound
and biopsy may reveal the
underlying cause.
Pericardial disease • May present with chest • ECG may show electrical
pain, typically worse on alternans or ST elevation
lying down, swallowing and T wave flattening or
or coughing; tachycardia; inversion. Echocardiography
dyspnoea; cough; oedema; may detect pericardial
fatigue; and low-grade fever. effusion, tamponade, and
Pericardial friction rub may pericardial fibrosis. CT scan
be heard at the left sternal or MRI may show thickened
border or apex. pericardium. Pericardial
biopsy may reveal the
underlying cause.
Venous stasis • Oedema affects lower limbs • Doppler examination may

only, and varicose veins may detect incompetent valves in
be present. Skin over the varicose veins.
lower legs may be darkened,
with ulceration.
Deep venous thrombosis • Typically causes pain, • D-dimer test may be positive.
swelling, and tenderness of Ultrasound scan or contrast
one calf, which becomes red venography may detect an
and warm. area of thrombosis.
Criteria
New York Heart Association (NYHA) classification[97]
This classification is symptom-based and has primarily been used as shorthand to describe functional
DIAGNOSIS
limitations. Heart failure symptoms may progress from one class to the next in a given patient, but can
also follow the path in reverse; for example, a patient with NYHA class IV symptoms might have quick
improvement to class III with diuretic therapy alone.
• Class I: Mild. No limitation of physical activity. Ordinary physical activity does not cause undue fatigue,
palpitations, or dyspnoea.
• Class II: Mild. Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity
results in fatigue, palpitations, or dyspnoea.
• Class III: Moderate. Marked limitation of physical activity. Comfortable at rest, but gentle activity
causes fatigue, palpitations, or dyspnoea.
• Class IV: Unable to carry out any physical activity without discomfort. Symptoms of cardiac
insufficiency at rest. If any physical activity is undertaken, discomfort is increased.
Screening
There is no single test for screening the asymptomatic population. Heart failure is a clinical diagnosis and as
such could simply rely on a thorough history and careful physical examination of the population to be tested.
B-type natriuretic peptide (BNP) has recently been used as a screening tool for identifying structural
heart disease in the general population. In one study, the sensitivity and specificity of BNP testing for
identification of structural heart disease were 61% and 92%, respectively.[98] When sex-specific analyses
were performed, sensitivity and specificity were 61% and 91% in men, and 50% and 95% in women,
respectively. Although the performance of BNP testing on the basis of these figures might seem suboptimal
for the population as a whole, efficacy was improved in subgroups with a high prevalence of heart disease,
such as the cohort aged 65 years and older, as well as the cohort having cardiovascular risk factors such
as hypertension or diabetes. In another trial, blood N-terminal pro-brain natriuretic peptide concentrations
were found to play an important role in stratifying older people into left ventricular dysfunction risk groups.
The neurohormone was an independent marker for death or admission for heart failure in the medium
term.[99] These results suggest that BNP testing for structural heart disease screening in community-based
populations might only be useful for cohorts with a high prevalence of heart disease. The American College
of Cardiology/American Heart Association/Heart Failure Society guidelines recommend that for patients
at risk of developing heart failure (identified by the presence of hypertension, diabetes mellitus, or known
vascular disease), natriuretic peptide biomarker-based screening followed by team-based care, including a
cardiovascular specialist optimising guideline-directed management and therapy, can be useful to prevent the
development of left ventricular dysfunction (systolic or diastolic) or new-onset heart failure. However, further
studies are needed to determine cost-effectiveness, its impact on quality of life, and mortality rate.[80]
DIAGNOSIS
25
Chronic congestive heart failure Management
Approach
Goals of treatment of chronic CHF are to:
• Alleviate symptoms
• Delay progression
• Reduce mortality.
General principles of therapy

• In newly diagnosed patients with CHF, congestion and volume overload should be promptly treated
with diuretics, which may be given intravenously in the initial phase. Loop diuretics used for the
treatment of heart failure and congestion include furosemide, bumetanide, and torasemide.
• In patients with low left ventricular ejection fraction (LVEF), in addition to diuretics, ACE inhibitors,
beta-blockers, and aldosterone antagonists (e.g., spironolactone, eplerenone) should be added.
• In unstable patients, beta-blockers should be initiated only after stabilisation, optimisation of volume
status, and discontinuation of inotropes. Beta-blockers should be initiated at a low dose.
• In patients with CHF and reduced LVEF who are hospitalised with exacerbation of heart failure,
unless there is evidence of low cardiac output or haemodynamic instability or contraindication, both
ACE-inhibitors and beta-blockers should be continued.
Lifestyle changes
The success of pharmacological therapy is strongly related to, and greatly enhanced by, encouraging
the patient and his/her family to participate in various complementary non-pharmacological management
strategies. These mainly include lifestyle changes, dietary and nutritional modifications, exercise training,
and health maintenance.[100]
Initial drug treatments

Diuretics:
• All patients with symptoms and signs of congestion should receive diuretics, irrespective of the
LVEF. In patients with reduced LVEF, diuretics should always be used in combination with an ACE
inhibitor (or angiotensin-II receptor antagonist), a beta-blocker, and an aldosterone antagonist.
Loop diuretics used for the treatment of heart failure and congestion include furosemide,
bumetanide, and torasemide. The most commonly used agent appears to be furosemide, but some
patients may respond more favourably to another loop diuretic. In resistant cases, loop diuretics
should be combined with a thiazide diuretic (e.g., chlorothiazide, hydrochlorothiazide) or a thiazide-
like diuretic (e.g., metolazone, indapamide).
• Loop diuretics and thiazide diuretics differ in their pharmacological actions. Loop diuretics increase
excretion of up to 20% to 25% of the filtered load of sodium, enhance free-water clearance, and
maintain their efficacy unless renal function is severely impaired. In contrast, thiazide diuretics
increase the fractional excretion of sodium to only 5% to 10% of the filtered load, tend to decrease
MANAGEMENT
free-water clearance, and lose their effectiveness in patients with impaired renal function (i.e.,
creatinine clearance less than 40 mL/minute). Consequently, loop diuretics have emerged as the
preferred diuretic agents for use in most patients with heart failure; however, thiazide diuretics
may be preferred in patients with hypertension, heart failure, and mild fluid retention because they
confer more persistent antihypertensive effects.
• Careful monitoring of renal function and electrolytes is essential. The minimum dose of diuretic
should be used to relieve congestion, keep the patient asymptomatic, and maintain a dry weight.
ACE inhibitors or beta-blockers:
ACE inhibitors
• ACE inhibitors or beta-blockers may be used as first-line treatment. Both are equally important in
terms of survival benefit. It has not been shown that starting with an ACE inhibitor is better than
starting with a beta-blocker, but in practice most physicians start an ACE inhibitor first; the origin
of this practice is historical, as the benefits of ACE inhibitors were demonstrated 10 years before
those of beta-blockers. Also, most large-scale studies of beta-blockers were conducted using ACE-
inhibitor therapy as comparator or standard. If a patient cannot tolerate target doses of both an ACE
inhibitor and a beta-blocker when these drugs are co-administered, it is preferable to co-administer
lower doses of both drugs than to reach the target dose in one class and not be able to initiate the
other.
• ACE inhibitors have been shown to decrease the morbidity and mortality associated with heart
failure, and should be given to all patients with left ventricular (LV) dysfunction, symptomatic or
otherwise, unless there is a contraindication or prior intolerance to therapy.[2] [7]
Beta-blockers
• Beta-blockers have also been shown to decrease the morbidity and mortality associated with
heart failure.[2] [7] They are initiated at low doses and titrated to target dosage.[2] [101] One meta-
analysis found that irrespective of pre-treatment heart rate, beta-blockers reduced mortality in
patients with heart failure with reduced ejection fraction (HFrEF) in sinus rhythm.[102] Achieving
a lower heart rate is associated with better prognosis for patients in sinus rhythm but not those
with atrial fibrillation. Mortality was lower for patients in sinus rhythm randomised to beta-blockers
(hazard ratio: 0.73 vs. placebo; 95% confidence interval [CI] 0.67 to 0.79; P <0.001), regardless of
baseline heart rate (interaction P = 0.35). Beta-blockers had no effect on mortality in patients with
atrial fibrillation (hazard ratio: 0.96; 95% CI 0.81 to 1.12; P = 0.58) at any heart rate (interaction P
= 0.48).[102] However, this was a retrospective analysis and authors commented that background
therapy, including devices, may have changed since these trials were conducted and that the heart
rate was not measured in a standardised fashion across the trials. In a randomised trial of patients
with atrial fibrillation and HFrEF, during a median follow-up of 37 months, beta-blockers were
associated with significantly lower all-cause mortality (hazard ratio: 0.721; 95% CI 0.549 to 0.945;
P = 0.0180) but not hospitalisation (hazard ratio: 0.886; 95% CI 0.715 to 1.100; P = 0.2232).[103]
The result of this study supports the evidence-based recommendations for beta-blockers in patients
with HFrEF, whether or not they have associated atrial fibrillation.
• Although side effects can include bradycardia, worsening of reactive airway disease, and
worsening heart failure, these can often be avoided by careful patient selection, dose titration, and
close monitoring. Clinical improvement may be delayed and may take 2 to 3 months to become
MANAGEMENT
apparent. However, long-term treatment with beta-blockers can lessen the symptoms of heart
failure and improve clinical status.
Angiotensin-II receptor antagonists:
27
Angiotensin-II receptor antagonists are considered a reasonable alternative to ACE inhibitors in patients
with preserved or decreased LVEF who are intolerant of ACE inhibitors because of cough or angio-
oedema.[2] [104] Experience with these drugs in controlled clinical trials of patients with heart failure
is considerably less than that with ACE inhibitors. Nevertheless, valsartan and candesartan have
demonstrated benefit by reducing hospitalisations and mortality.[2] [105] In patients with evidence of left
ventricular dysfunction early after myocardial infarction, angiotensin-II receptor antagonists may be no
more effective than ACE inhibitors and may be no better tolerated. The combination of an ACE inhibitor
and an angiotensin-II receptor antagonist may produce more reduction of left ventricular size[106] and
may reduce the need for hospitalisation than either agent alone, although whether or not combination
therapy further reduces mortality remains unclear.[106] [107] [108] As an alternative to ACE inhibitors,
angiotensin-II receptor antagonists should be initiated in patients early post-infarct, but caution should be
used in patients in cardiogenic shock or with marginal renal output.[105]
Addition of an angiotensin-II receptor antagonist may be considered in persistently symptomatic patients

with heart failure and reduced LVEF who are already being treated with an ACE inhibitor and beta-
blockers and in whom an aldosterone antagonist is not indicated or tolerated.[2] Routine combined use
of ACE inhibitors with an aldosterone antagonist and an angiotensin-II receptor antagonist is potentially
harmful for patients with heart failure and is not recommended.[2] Combined use should be instigated
by a specialist and continued only with specialist supervision. Concomitant administration of an ACE
inhibitor, a beta-blocker, and an angiotensin-II receptor antagonist should be used with great caution and
perhaps initiated only in hospital under continuous blood pressure and renal function monitoring, because
it may provoke life-threatening hypotension and acute renal insufficiency. The CHARM trial showed that
this combination may confer added benefit with acceptable risk, but further studies are required.[109]
In one study, addition of olmesartan (an angiotensin-II receptor antagonist) to patients with New York
Heart Association (NYHA) class II to IV heart failure who had a history of hypertension or who had been
treated with antihypertensive medications and were already on ACE inhibitor and beta-blocker therapy
did not improve the clinical outcome and led to worsening of renal function.[110] In this study, subgroup
analysis showed that the addition of olmesartan to a combination of an ACE inhibitor and a beta-blocker
was associated with an increased incidence of primary end point, all-cause death, and renal dysfunction.
The routine combined use of all three inhibitors of the renin-angiotensin system cannot be recommended
at present. The European Medicines Agency's Pharmacovigilance Risk Assessment Committee has
advised that combining drugs that act on the renin-angiotensin system (e.g., ACE inhibitors, angiotensin-II
receptor antagonists) is not recommended, particularly in patients with diabetes-related kidney problems.
Where such a combination is considered absolutely necessary, it should be carried out under strict
specialist supervision with close monitoring.[111]
Renin inhibitors (e.g., aliskiren) should also not be combined with ACE inhibitors. In a study of patients
with chronic heart failure (NYHA class II to IV, ejection fraction of 35% or less) addition of aliskiren
to enalapril compared with enalapril alone led to more adverse events (hypotension and elevated
creatinine) without any benefit or difference in primary outcome of death from cardiovascular causes or
hospitalisation for heart failure.[112]
Angiotensin-II receptor antagonist plus neprilysin inhibitor:

MANAGEMENT
In HFrEF (NYHA class II to IV) and ejection fraction of 40% or less, which was later changed to an
ejection fraction of 35% or less, a combination of sacubitril, a neprilysin inhibitor, and valsartan, an
angiotensin-II receptor antagonist, was superior to enalapril in reducing mortality and heart failure
hospitalisation.[113] The drug combination has been approved in the US and in Europe for the treatment
of heart failure. In this study the ejection fraction was 29 ± 6.1% in the sacubitril/valsartan group and 29.4
± 6.3% in the enalapril group.[113]
Sacubitril/valsartan has been found to improve a patient's physical and social activities compared with
enalapril.[114]
Sacubitril/valsartan is recommended as a replacement for an ACE inhibitor in patients who remain

symptomatic despite optimal treatment with an ACE inhibitor, a beta-blocker, and a mineralocorticoid-
receptor antagonist.[1] It is recommended for patients who fit the profile of the study showing beneficial
effects of this combination (i.e., patients in NYHA class II to IV with LVEF of 35% or <35%).[113] The
American Heart Association/American College of Cardiology/Heart Failure Society of America guidelines
recommend that, in patients with chronic NYHA class II or III who tolerate an ACE inhibitor or angiotensin-
II receptor antagonist, these drugs should be replaced by an angiotensin-II receptor antagonist plus
neprilysin inhibitor to further reduce morbidity and mortality.[80] Concomitant administration of an
angiotensin-II receptor antagonist plus a neprilysin inhibitor with an ACE inhibitor, or within 36 hours of the
last dose of an ACE inhibitor, is not recommended.[80]
Treatment with sacubitril/valsartan reduces cardiovascular death by reducing both worsening heart failure
and sudden cardiac death.[115]
Hydralazine and nitrates:
The addition of a combination of hydralazine and a nitrate is reasonable for patients with reduced LVEF
who are already taking an ACE inhibitor and beta-blocker for symptomatic heart failure and who have
persistent symptoms,[2] and has demonstrated benefit in black patients with heart failure.[116] [117] The
combined use of hydralazine and isosorbide dinitrate may also be considered as a therapeutic option in
patients who are intolerant of ACE inhibitors.[2] This combination may be a useful alternative in patients
intolerant to both ACE inhibitors and angiotensin-II receptor antagonists.[2]
A combination of hydralazine and isosorbide dinitrate can be useful to reduce morbidity or mortality in
patients with current or prior symptomatic HFrEF who cannot be given an ACE inhibitor or angiotensin-
II receptor antagonist because of drug intolerance, hypotension, or renal insufficiency, unless
contraindicated.[2] The American College of Cardiology Foundation/American Heart Association
guidelines recommend the combination of hydralazine and isosorbide dinitrate to "reduce morbidity
and mortality in patients self-described as African Americans with NYHA class III to IV HFrEF receiving
optimal therapy with ACE inhibitors and beta blockers, unless contraindicated".[2]
Anticoagulants:
At present there is little evidence from long-term studies to recommend antiplatelet therapy or oral
anticoagulation in patients with heart failure in sinus rhythm, and antiplatelet agents versus control or
anticoagulation for heart failure in sinus rhythm.[118]
• A study comparing warfarin and aspirin in patients with heart failure and sinus rhythm showed no
significant difference in the combined outcomes of stroke, intracerebral haemorrhage, and death.
MANAGEMENT
Warfarin reduced ischaemic stroke at the expense of an increased bleeding risk.[119]

• Although oral anticoagulants are indicated in certain groups of patients with heart failure (e.g.,
patients with atrial fibrillation), the available data do not support their routine use in heart failure
patients who remain in sinus rhythm.[118]
29
Digoxin for patients with heart failure
Digoxin can be beneficial in patients with current or prior symptoms of heart failure or reduced LVEF,
especially those with atrial fibrillation. When added to ACE inhibitors, beta-blockers, and diuretics, digoxin
can reduce symptoms, prevent hospitalisation, control rhythm, and enhance exercise tolerance.[120]
Digoxin reduces the composite end point of mortality or hospitalisations in ambulatory patients with
chronic heart failure with NYHA class III or IV symptoms, LVEF <25%, or cardiothoracic ratio of >55% and
should be considered in these patients.[121]
Digoxin reduces the composite end point of mortality or hospitalisations, but does not reduce all-cause
mortality.[121] Digoxin should be used cautiously with plasma level monitoring. One meta-analysis
suggests that digoxin use in patients with heart failure is associated with a higher risk of all-cause
mortality.[122]
One systematic review and meta-analysis of observational and controlled trial data showed that digoxin
has a neutral effect on mortality in randomised trials and reduces hospital admissions.[123]
Aldosterone antagonists in moderate-to-severe heart failure

Aldosterone antagonists (also known as mineralocorticoid receptor antagonists) decrease the morbidity
and mortality associated with symptomatic chronic heart failure.
Aldosterone antagonists (spironolactone and eplerenone) are recommended in patients with NYHA
class II to IV heart failure who have LVEF of 35% or less, unless contraindicated.[2] They are also
recommended to reduce mortality and morbidity following acute myocardial infarction in patients with
LVEF of 40% or less who develop symptoms of heart failure or have a history of diabetes mellitus, unless
contraindicated.[2] [124]
Aldosterone antagonists should be initiated after titration of standard medical therapy. Spironolactone and
eplerenone can both cause hyperkalaemia, and precautions should be taken to minimise the risk. In the
EPHESUS trial, the addition of eplerenone to standard care did not increase the risk of hyperkalaemia
when potassium was regularly monitored.[125]
Ivabradine
Ivabradine is approved for use in patients with heart failure and symptoms in spite of drug therapy. The
UK National Institute for Health and Care Excellence has approved it for patients with NYHA class II to IV
heart failure, sinus rate of over 75 bpm, and ejection fraction <35%.[126] In the US, the Food and Drug
Administration (FDA) has approved it to reduce the risk of hospitalisation for worsening heart failure in
patients with stable, symptomatic chronic heart failure, with LVEF ≤35%, who are in sinus rhythm with a
resting heart rate ≥70 beats per minute, and are either on a maximum dose of beta-blockers or have a
contraindication to beta-blockers.
In a randomised, double-blind, placebo-controlled trial, addition of ivabradine to standard background

therapy in patients with stable coronary artery disease without clinical heart failure (no evidence of left
ventricular systolic dysfunction in the overall study population, mean ejection fraction was 56.4%) did not
MANAGEMENT
improve the outcome. In the subgroup analysis of this study, ivabradine was associated with an increase
in the incidence of the primary end point (death from cardiovascular causes or non-fatal myocardial
infarction) among patients who had angina of Canadian Cardiovascular Society class II or higher but not
among patients without angina or those who had angina of class I. Ivabradine was associated with an
increased incidence of bradycardia, QT prolongation, and atrial fibrillation.[124]
Vasopressin antagonists
Use of vasopressin antagonists such as tolvaptan can be considered for patients with symptomatic or
severe hyponatraemia (<130 mmol/L) and persistent congestion despite standard therapy, to correct
hyponatraemia and related symptoms.[2] [127]
Heart transplant and medical devices

Cardiac transplantation is currently the only established surgical approach, but it is available to fewer than
2500 patients in the US each year.[128] [129] [130] Current indications for cardiac transplantation focus
on the identification of patients with severe functional impairment, dependence on intravenous inotropic
agents, recurrent life-threatening ventricular arrhythmias, or angina that is refractory to all currently
available treatments.[2] [129] [130] [131]
Implantable cardioverter-defibrillators (ICDs) have been shown to decrease mortality in patients with heart
failure, both ischaemic and non-ischaemic. The SCD-Heft trial enrolled patients who had left ventricular
dysfunction and no prior history of syncope or sustained ventricular tachycardia, and included patients
with a prior myocardial infarction and no prior coronary artery disease. Use of ICDs led to a 23% relative
mortality risk reduction at 5 years.[132]
An ICD is recommended in the following situations:[2]
1. For primary prevention of sudden cardiac death in selected patients with both non-ischaemic and
ischaemic heart failure, at least 40 days post myocardial infarction, LVEF <35%, New York Heart
Association (NYHA) class II or III symptoms on guideline-directed medical therapy, and expected to
live for >1 year, or LVEF <30%, NHYA class I, on guideline-directed medical therapy, and expected
to live for >1 year
2. As secondary prevention to prolong survival in patients with current or prior symptoms of
heart failure and reduced LVEF who have a history of cardiac arrest, ventricular fibrillation, or
haemodynamically destabilising ventricular tachycardia.
It has been estimated that one quarter to one third of patients with heart failure have left bundle-branch
block: that is, manifest a QRS duration greater than 120 milliseconds (ms).[133] Patients with heart
failure who have left bundle-branch block, known as ventricular dyssynchrony, have a poorer prognosis
than those without left bundle-branch block.[2] Studies have shown that, in these patients, cardiac re-
synchronisation therapy (CRT) decreases hospitalisation and, when combined with an ICD, significantly
reduces mortality.[134] [135] [136] [137] [138] [139] In patients who have conduction delay and left
ventricular dysfunction, biventricular pacemakers have been shown to improve exercise tolerance and
quality of life while decreasing morbidity and mortality.[134] [135] [136] [137] [139] [140] [141] [142] The
CARE-HF study randomised patients with a widened QRS, LVEF of 35% or less, and persistent moderate
or severe symptoms of heart failure despite pharmacological therapy, to implantation of a CRT device
or not.[143] The main study observed substantial benefits on morbidity and mortality that persisted or
increased with longer follow-up.[144] [145] [146] [147] [148] [149] [150] [151] [152] [153] [154] Reduction
in mortality was due to fewer deaths from heart failure and from reduced sudden death.[144]
Long-term data from the REVERSE study suggest that improvements in left ventricular function and
MANAGEMENT
remodelling can be sustained for over 5 years.[155] [156]
According to the American College of Cardiology Foundation/American Heart Association guidelines, the
recommendations for the use of CRT devices in heart failure are as follows.[2]
31
1. CRT is indicated in patients who have LVEF of 35% or less; sinus rhythm; left bundle-branch block
(LBBB) with a QRS duration of 150 ms or greater; NYHA class II, III, or ambulatory IV symptoms on
guideline-directed medical therapy.
2. CRT can be useful in patients who have LVEF of 35% or less; sinus rhythm; a non-LBBB with a
QRS duration of 150 ms or greater; NYHA class III/ambulatory IV symptoms on guideline-directed
medical therapy.
3. CRT can be useful in patients who have LVEF of 35% or less; sinus rhythm; LBBB with a QRS
duration of 120 to 149 ms; NYHA class II, III, or ambulatory IV symptoms on guideline-directed
medical therapy.
4. CRT can be useful in patients with atrial fibrillation and LVEF of 35% or less on guideline-directed
medical therapy if (a) the patient requires pacing or otherwise meets the CRT criteria; and (b)
atrioventricular nodal ablation or pharmacological rate control will allow near 100% ventricular
pacing with CRT.
5. CRT can be useful for patients on guideline-directed medical therapy who have LVEF of 35% or
less and are undergoing device implantation with anticipated requirement for significant (>40%)
ventricular pacing.
American Heart Association guidance outlines the indication and evidence behind the use of mechanical
circulatory support in patients with heart failure.[157] Mechanical circulatory support, which includes
ventricular assist devices, helps to maintain sufficient end organ perfusion by unloading the heart and is
considered in carefully selected patients who have end-stage heart failure, despite optimal medical and
device therapy, and in whom definite management (e.g., cardiac transplantation) or cardiac recovery is
anticipated.[1] [2]
Currently in the US, the accepted indications for implantation of a durable left ventricular assist device
(LVAD) are bridge to transplantation and destination therapy (permanent pump implantation in patients
not eligible for cardiac transplantation).[158] In clinical practice, another indication for LVAD is to provide a
bridge to decisions about future care.
The European Society of Cardiology has outlined the various indications for mechanical circulatory
support:[1] [2]
• Bridge to decision/bridge to bridge: use of short-term support (e.g., extracorporeal life support
[ECLS] or extracorporeal membrane oxygenation [ECMO] in patients with cardiogenic shock until
haemodynamics and end-organ perfusion are stabilised, contraindications for long-term support
are excluded, and therapeutic options including long-term VAD therapy or heart transplant can be
evaluated.
• Bridge to candidacy: use of support (usually LVAD) to make ineligible patient eligible for heart
transplant.
• Bridge to transplantation: use of LVAD or biventricular assist device to keep high-risk transplant
candidate alive until donor organ becomes available.
• Bridge to recovery: use of support (usually LVAD) to keep the patient alive until cardiac function
recovers sufficiently to remove it.
• Destination therapy: long-term use of LVAD as alternative to heart transplant.
MANAGEMENT
Some of the absolute contraindications for providing durable mechanical support include irreversible
hepatic, renal and neurological disease, medical non-adherence, and severe psychosocial
limitations.[159]
Please see our topic on Acute heart failure for more information.
Treatment algorithm overview

Please note that formulations/routes and doses may differ between drug names and brands, drug
formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
MANAGEMENT
33
Acute ( summary )
tolerance to ACE inhibitors
1st ACE inhibitor or sacubitril/valsartan
plus lifestyle changes
plus beta-blocker
adjunct diuretic
adjunct aldosterone antagonist
adjunct hydrala zine + isosorbide dinitrate
adjunct digoxin
adjunct ivabradine
adjunct vasopressin antagonist
intolerance to ACE inhibitors
1st beta-blocker + angiotensin-II receptor

antagonist
adjunct diuretic
adjunct digoxin
adjunct ivabradine
2nd hydrala zine + isosorbide dinitrate
plus beta-blocker
adjunct diuretic
adjunct digoxin
adjunct ivabradine

MANAGEMENT
Ongoing ( summary )
refractory to optimal medical
treatment
LVEF <35%: no left 1st implantable cardioverter-defibrillator (ICD)

bundle-branch block
2nd mechanical circulatory support
3rd cardiac transplantation
LVEF <35%: left bundle- 1st cardiac re-synchronisation therapy with

branch block biventricular pacemaker (CRT-P)/cardiac
resynchronisation therapy-defibrillator
(CRT-D)
2nd left ventricular assist device (LVAD)
MANAGEMENT
35
Treatment algorithm
Please note that formulations/routes and doses may differ between drug names and brands, drug
formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
MANAGEMENT
Acute
tolerance to ACE inhibitors
1st ACE inhibitor or sacubitril/valsartan

Primary options
» captopril: 6.25 to 50 mg orally three times

daily
OR
» enalapril: 2.5 to 20 mg orally twice daily
OR
» fosinopril: 5-40 mg orally once daily
OR
» lisinopril: 2.5 to 40 mg orally once daily
OR
» perindopril: 2-16 mg orally once daily
OR
» quinapril: 5-20 mg orally twice daily
OR
» ramipril: 1.25 to 10 mg orally once daily
OR
» trandolapril: 1-4 mg orally once daily
OR
» sacubitril/valsartan: treatment-naive
patients: 24 mg (sacubitril)/26 mg (valsartan)
orally twice daily initially, increase gradually
according to response, maximum 97 mg
(sacubitril)/103 mg (valsartan); treatment-
experienced: 49 mg (sacubitril)/51 mg
(valsartan) orally twice daily initially, increase
gradually according to response, maximum
97 mg (sacubitril)/103 mg (valsartan)
Patients not taking an ACE inhibitor or
MANAGEMENT
angiotensin-II receptor antagonist should

be started on a lower dose. Patients who
were being treated with an ACE inhibitor or
angiotensin-II receptor antagonist should
be started on a higher dose. Allow 36 hours
37
Acute
between stopping an ACE inhibitor and
starting this drug.
» ACE inhibitors have been shown to decrease

the morbidity and mortality associated with
heart failure, and should be given to all
patients with left venticular dysfunction, both
asymptomatic and symptomatic, unless there
is a contraindication or prior intolerance to
therapy.[2] [7]
» ACE inhibitors should be used with caution

in patients in cardiogenic shock, with marginal
renal output or hyperkalaemia.
» If patients have an idiosyncratic reaction, with

angio-oedema, ACE inhibitors should not be
rechallenged.
» However, in heart failure with reduced ejection

fraction (New York Heart Association [NYHA]
class II to IV and ejection fraction of 35% or less)
a combination of sacubitril, a neprilysin inhibitor,
and valsartan, an angiotensin-II receptor
antagonist, is superior to enalapril in reducing
mortality and heart failure hospitalisation.[113]
The drug combination has been approved
in the US and in Europe for the treatment of
heart failure. The American Heart Association/
American College of Cardiology/Heart Failure
Society of America guidelines recommend that,
in patients with chronic NYHA class II or III
who tolerate an ACE inhibitor or angiotensin-
II receptor antagonist, these drugs should
be replaced by an angiotensin-II receptor
antagonist plus neprilysin inhibitor to further
reduce morbidity and mortality.[80] Concomitant
administration of an angiotensin-II receptor
antagonist plus neprilysin with an ACE inhibitor,
or within 36 hours of the last dose of an ACE
inhibitor, is not recommended.[80]
Treatment recommended for ALL patients in
selected patient group
» Dietary sodium intake is an easily modifiable
factor that complements pharmacological
therapy for heart failure. For stage A and B heart
failure (stage A: at high risk for heart failure but
without structural heart disease or symptoms of
heart failure; stage B: structural heart disease
MANAGEMENT
but without signs or symptoms of heart failure),

the recommendation is to limit sodium intake to
1.5 g/day. For stage C and D heart failure (stage
C: structural heart disease with prior or current
symptoms of heart failure; stage D: refractory
heart failure requiring specialised interventions),
Acute
the recommendation is to limit sodium intake to
at least 3 g/day.[2]
» Fluid restriction is mostly used as an in-

hospital complementary measure in cases
of acute exacerbations. In addition, fluid
restriction may be warranted in cases of
severe hyponatraemia. However, it would be
of importance to advise the patient to keep a
daily intake/output balance at home. Patients
are advised to monitor their weight daily and to
immediately contact their healthcare provider if a
specified change in weight occurs.
» Heart failure patients need continuous and

close monitoring of their health. A variety of
programmes have been shown to decrease
morbidity and re-hospitalisation in this context,
including home nursing, telephone advice/triage,
telemedicine services, and specialised heart
failure clinic-based care.[160]
» Exercise training has also been shown to be

beneficial.[100]
plus beta-blocker
Primary options
» carvedilol: 3.125 mg orally (immediate-

release) twice daily initially, increase
according to response, maximum 50 mg/day
(body weight ≤85 kg) or 100 mg/day (body
weight >85 kg)
Secondary options
» metoprolol: 12.5 to 200 mg orally

(extended-release) once daily
OR
» bisoprolol: 1.25 mg orally once daily initially,

increase according to response, maximum 10
mg/day
OR
» nebivolol: 1.25 mg orally once daily initially,

MANAGEMENT
mg/day
» All patients with chronic heart failure receive

a beta-blocker once established on an ACE
inhibitor, unless there is a contraindication based
39
Acute
on bradycardia, reactive airway disease, and
unstable or low-output heart failure.[2] [7]
» Carvedilol seems superior to metoprolol,[161]

although there is no evidence of superiority to
other beta-blockers. In the SENIORS study,
nebivolol, a cardioselective beta-blocker with
nitric oxide-mediated vasodilating properties,
was found to be an effective and well-tolerated
treatment for heart failure in patients aged
70 years or more.[162] Data suggest that
initiation with moderate doses of nebivolol is
not associated with the adverse haemodynamic
effects usually observed with other beta-blockers
in patients with heart failure; therefore, a long
up-titration period may not be necessary with
nebivolol.[163]
» Beta-blockers have been shown to decrease

the morbidity and mortality associated with heart
failure.[2] [7] They are initiated at low doses and
titrated to target dosage.[2] [101] One meta-
analysis found that irrespective of pre-treatment
heart rate, beta-blockers reduced mortality in
patients with heart failure with reduced ejection
fraction in sinus rhythm.[102]
adjunct diuretic
Treatment recommended for SOME patients in
Primary options
» furosemide: 20-80 mg/dose orally initially,

increase by 20-40 mg/dose increments every
6-8 hours according to response, maximum
600 mg/day
OR
» bumetanide: 0.5 to 1 mg orally once or

twice daily initially, increase according to
response, maximum 10 mg/day
OR
» torasemide: 5-20 mg orally once daily

initially, increase according to response,
maximum 40 mg/day
OR
MANAGEMENT
» chlorothiazide: 250-500 mg orally once or

twice daily, maximum 1000 mg/day
OR
Acute
» hydrochlorothiazide: 25 mg orally once or
twice daily, increase according to response,
maximum 200 mg/day
OR
» indapamide: 2.5 to 5 mg orally once daily
OR
» metolazone: 2.5 to 20 mg orally once daily
Secondary options
» amiloride: 5-20 mg orally once daily
OR
» triamterene: 50-100 mg orally twice daily

maximum 300 mg/day
» Diuretics should be considered for patients

who have evidence of, or a prior history of, fluid
retention.[2] They should generally be combined
with an ACE inhibitor and a beta-blocker. All
patients with symptoms and signs of congestion
should receive diuretics, irrespective of the left
ventricular ejection fraction (LVEF).
» Loop diuretics used for the treatment of heart

failure and congestion include furosemide,
bumetanide, and torasemide. The most
commonly used agent appears to be furosemide,
but some patients may respond more favourably
to another loop diuretic. In resistant cases,
loop diuretics should be combined with
a thiazide diuretic (e.g., chlorothiazide,
hydrochlorothiazide) or a thiazide-like diuretic
(e.g., metolazone, indapamide). Careful
monitoring of renal function and electrolytes is
essential in these patients.
» The minimum dose of diuretic should be

used to relieve congestion, keep the patient
asymptomatic, and maintain a dry weight. In
patients with stable congestive heart failure,
loop diuretics are the preferred agent. In patients
with hypertension and only mild fluid retention, a
thiazide diuretic may be considered.
MANAGEMENT
» Diuretics produce symptomatic benefits more

rapidly than any other drug for heart failure. They
can relieve pulmonary and peripheral oedema
within hours or days. Few patients with heart
failure and fluid retention can maintain sodium
balance without the use of diuretic drugs.[164]
41
Acute
» Diuretics alone are unable to maintain the
clinical stability of patients with heart failure
for long periods of time,[164] but the risk of
clinical decompensation can be reduced when
they are combined with an ACE inhibitor and
a beta-blocker.[165] Diuretics should be used
only in combination with an ACE inhibitor (or
angiotensin-II receptor antagonist), a beta-
blocker, and an aldosterone antagonist in
patients with reduced LVEF.
» In intermediate-term studies, diuretics have

been shown to improve cardiac function,
symptoms, and exercise tolerance in patients
with heart failure.[164] [166] There have been
no long-term studies of diuretic therapy in heart
failure, and thus their effects on morbidity and
mortality are not known.
» Amiloride and triamterene (potassium-

sparing diuretics) should be used with caution
with aldosterone antagonists, because of the
increased risk of developing hyperkalaemia.
Close monitoring of serum potassium levels is
suggested in this situation.
Primary options
» spironolactone: 25-100 mg orally once daily
OR
» eplerenone: 25-50 mg orally once daily
» Aldosterone antagonists, also known as

mineralocorticoid receptor antagonists (e.g.,
spironolactone and eplerenone), decrease
symptomatic chronic heart failure.
» Aldosterone antagonists are recommended in

patients with New York Heart Association class
II to IV heart failure who have left ventricular
ejection fraction (LVEF) of 35% or less, unless
contraindicated.[2] They are also recommended
to reduce mortality and morbidity following acute
myocardial infarction in patients with LVEF of
40% or less who develop symptoms of heart
MANAGEMENT
failure or have a history of diabetes mellitus,

unless contraindicated.
» Aldosterone antagonists should be initiated

after titration of standard medical therapy.
Spironolactone and eplerenone can both cause
Acute
hyperkalaemia, and precautions should be taken
to minimise the risk.
» These agents should be used with caution

in patients with renal dysfunction and
hyperkalaemia. They should not be initiated
in patients with a serum creatinine above 221
micromols/L (>2.5 mg/dL) or a serum potassium
above 5.0 millimols/L (>5.0 mEq/dL) and should
be used with caution in patients with serum
creatinine below 221 micromols/L (<2.5 mg/dL)
plus a serum potassium above 5.0 millimols/
L (>5.0 mEq/dL). Patients should discontinue
potassium repletion.
» Adherence to intensive monitoring of renal

function and potassium levels has been shown
to prevent hyperkalaemia, which is as likely
to occur with eplerenone therapy as it is with
spironolactone therapy.

Primary options
» isosorbide dinitrate: 20-40 mg orally

(immediate-release) three times daily
-and-
» hydralazine: 10-100 mg orally three times
daily
OR
» isosorbide dinitrate/hydralazine: 20 mg
(isosorbide dinitrate)/37.5 mg (hydralazine)
orally three times daily, maximum 40 mg
(isosorbide dinitrate)/75 mg (hydralazine)
three times daily
» A combination of hydralazine and isosorbide

dinitrate can be useful to reduce morbidity
or mortality in patients with current or prior
symptomatic heart failure with reduced ejection
MANAGEMENT
fraction (HFrEF) who cannot be given an ACE

inhibitor or angiotensin-II receptor antagonist
because of drug intolerance, hypotension, or
renal insufficiency, unless contraindicated.[2]
The American College of Cardiology Foundation/
American Heart Association guidelines
43
Acute
recommend the combination of hydralazine and
isosorbide dinitrate to "reduce morbidity and
mortality in patients self-described as African
Americans with NYHA class III to IV HFrEF
receiving optimal therapy with ACE inhibitors and
beta blockers, unless contraindicated".[2]
» Nitrate therapy may decrease symptoms of

dyspnoea at night and during exercise and may
improve exercise tolerance in patients who have
persistent limitations despite optimisation of
other therapies.[167] [168]
» Development of nitrate tolerance seems to

be minimised by prescription of a nitrate-free
interval of at least 10 hours.[2] Carvedilol use
has been shown to prevent nitrate tolerance in
patients with CHF.[169] [170]
» Hydralazine may interfere with the biochemical

and molecular mechanisms responsible for the
development of nitrate tolerance.[171] [172]
» A combination pill containing 37.5 mg

hydralazine and 20 mg isosorbide dinitrate is
available, approved specifically for self-identified
black patients with CHF.
adjunct digoxin
Primary options
» digoxin: 0.125 to 0.5 mg orally once daily
» Digoxin can be beneficial in patients with

reduced left ventricular ejection fraction (LVEF),
especially those with atrial fibrillation.
» When added to ACE inhibitors, beta-blockers,

and diuretics, digoxin can reduce symptoms,
prevent hospitalisation, control rhythm, and
enhance exercise tolerance.
» Digoxin reduces the composite end point

of mortality or hospitalisations in ambulatory
patients with chronic heart failure with New York
Heart Association class III or IV symptoms,
LVEF <25%, or cardiothoracic ratio of >55% and

MANAGEMENT
of mortality or hospitalisations, but does not

reduce all-cause mortality.[121] Digoxin should
be used cautiously with plasma level monitoring;
one meta-analysis suggests that digoxin use in
patients with heart failure is associated with a
higher risk of all-cause mortality.[122]
Acute
» Overt digitalis toxicity is commonly associated
with serum digoxin levels >2.6 nanomols/L (2
nanograms/mL). However, toxicity may occur
with lower levels, especially if hypokalaemia,
hypomagnesaemia, or hypothyroidism co-
exists.[173] [174]
» Low doses (0.125 mg/day or every other day)

should be used initially if the patient is over 70
years old, has impaired renal function, or has a
low lean body mass.[175]
» Higher doses (e.g., 0.375 to 0.5 mg/day) are

rarely used or needed.
» There is no reason to use loading doses of

digoxin to initiate therapy.
adjunct ivabradine
Primary options
» ivabradine: 5 mg orally twice daily initially,

may increase to 7.5 mg twice daily after 2
weeks if necessary; adjust dose according to
heart rate
» Ivabradine may be an option for patients with

New York Heart Association class II, III, or IV
heart failure who have a sinus rate >75 beats per
minute and an ejection fraction <35%, and who
remain symptomatic despite optimal therapy. It
can also be used in patients who are unable to
take beta-blockers.
» Its use should be initiated by a specialist

cardiologist and only after a stabilisation period
of 4 weeks on optimised standard therapy.[126]
» In a randomised, double-blind, placebo-

controlled trial, addition of ivabradine to standard
background therapy in patients with stable
coronary artery disease without clinical heart
failure (no evidence of left ventricular systolic
dysfunction in the overall study population,
mean ejection fraction was 56.4%) did not
improve the outcome. In the subgroup analysis
of this study, ivabradine was associated with
an increase in the incidence of the primary end
point (death from cardiovascular causes or
non-fatal myocardial infarction) among patients
MANAGEMENT
who had angina of Canadian Cardiovascular

Society class II or higher but not among patients
without angina or those who had angina of class
I. Ivabradine was associated with an increased
45
Acute
incidence of bradycardia, QT prolongation, and
atrial fibrillation.[124]
Primary options
» tolvaptan: 15 mg orally once daily initially,

increase gradually according to response,
maximum 60 mg/day for up to 30 days
» Considered for patients with symptomatic

or severe hyponatraemia (<130 mmol/L)
and persistent congestion despite standard
therapy, to correct hyponatraemia and related
symptoms.[2] [127]
intolerance to ACE inhibitors
1st beta-blocker + angiotensin-II receptor

antagonist
Primary options

weight >85 kg)
--AND--
» candesartan: 4-32 mg orally once daily
-or-
» losartan: 25-100 mg orally once daily
-or-
» valsartan: 40-160 mg orally twice daily
Secondary options

-or-
mg/day
-or-
mg/day
--AND--
» candesartan: 4-32 mg orally once daily
MANAGEMENT
-or-
» losartan: 25-100 mg orally once daily
-or-
» valsartan: 40-160 mg orally twice daily
Acute
» All patients with chronic heart failure receive a
beta-blocker, unless there is a contraindication
based on bradycardia, reactive airway disease,
and unstable or low-output heart failure.[2] [7]

nebivolol.[163]
» Angiotensin-II receptor antagonists should be

added instead of ACE inhibitors in all patients
who are intolerant of ACE inhibitors because
of cough or angio-oedema.[2] Valsartan and
candesartan have demonstrated benefit by
reducing hospitalisations and mortality.[105]
» Angiotensin-II receptor antagonists are as

likely to produce hypotension, worsening renal
function, and hyperkalaemia as ACE inhibitors.
Although angio-oedema is much less frequent,
there are cases of patients who developed
angio-oedema to both ACE inhibitors and later to
angiotensin-II receptor antagonists.
therapy for heart failure. Thus the patient and
family are advised to follow a daily dietary
sodium intake between 2 and 3 g. Further
restriction to 1 to 2 g/day may be necessary for
patients with advanced symptoms refractory to
therapy.

MANAGEMENT

47
Acute
failure-clinic-based care.

beneficial.[100]
adjunct diuretic
Primary options

600 mg/day
OR

OR

maximum 40 mg/day
OR

OR

maximum 200 mg/day
OR
OR
MANAGEMENT
Secondary options
Acute
OR

maximum 300 mg/day


to other loop diuretics. In resistant cases,

asymptomatic, and maintain a dry weight. In


an angiotensin-II receptor antagonist), a beta-
MANAGEMENT

with heart failure.[164] [166]
49
Acute
» There have been no long-term studies of
diuretic therapy in heart failure; therefore, their
effects on morbidity and mortality are not known.

Primary options
OR


unless contraindicated.[2]


MANAGEMENT

Acute

Primary options

-and-
daily
OR
three times daily
» The combined use of hydralazine and

isosorbide dinitrate may be considered as a
therapeutic option in patients who are intolerant
of ACE inhibitors and angiotensin-II receptor
antagonists.[176] [177] A combination of
hydralazine and isosorbide dinitrate can be
useful to reduce morbidity or mortality in
patients with current or prior symptomatic
heart failure with reduced ejection fraction
(HFrEF) who cannot be given an ACE inhibitor
or angiotensin-II receptor antagonist because
of drug intolerance, hypotension, or renal
insufficiency, unless contraindicated.[2] The
American College of Cardiology Foundation/
MANAGEMENT


51
Acute


» A combination pill containing 37.5 mg

hydralazine and 20 mg isosorbide dinitrate is
available, approved specifically for self-identified
black patients with CHF.
adjunct digoxin
Primary options




of mortality or hospitalisations, but does not
reduce all-cause mortality.[121] Digoxin should
be used cautiously with plasma level monitoring.
One meta-analysis suggests that digoxin use in
patients with heart failure is associated with a
higher risk of all-cause mortality.[122]

MANAGEMENT

exists.[173] [174]

Acute


adjunct ivabradine
Primary options

heart rate

take beta-blockers.


MANAGEMENT

Primary options
53
Acute

symptoms.[2] [127]
2nd hydrala zine + isosorbide dinitrate
Primary options

-and-
daily
OR
three times daily
» The combined use of hydralazine and

isosorbide dinitrate may be considered as a
therapeutic option in patients who are intolerant
of ACE inhibitors and angiotensin-II receptor
antagonists.[176] [177] A combination of
hydralazine and isosorbide dinitrate can be
useful to reduce morbidity or mortality in
patients with current or prior symptomatic
heart failure with reduced ejection fraction
(HFrEF) who cannot be given an ACE inhibitor
or angiotensin-II receptor antagonist because
of drug intolerance, hypotension, or renal
insufficiency, unless contraindicated.[2] The
American College of Cardiology Foundation/

MANAGEMENT


Acute

plus beta-blocker
Primary options

weight >85 kg)
Secondary options

OR

mg/day
OR

mg/day
» All patients with chronic heart failure receive a

beta-blocker, unless there is a contraindication
based on bradycardia, reactive airway disease,
and unstable or low-output heart failure.[2] [7]

MANAGEMENT

nebivolol.[163]
55
Acute
therapy for heart failure. Thus the patient and
family are advised to follow a daily dietary
sodium intake between 2 and 3 g. Further
restriction to 1 to 2 g/day may be necessary for
patients with advanced symptoms refractory to
therapy.


failure-clinic-based care.

beneficial.[100]
adjunct diuretic
Primary options

600 mg/day
OR

OR
MANAGEMENT

maximum 40 mg/day
OR
Acute

OR

maximum 200 mg/day
OR
OR
Secondary options
OR

maximum 300 mg/day


to other loop diuretics. In resistant cases,

MANAGEMENT

asymptomatic and maintain a dry weight. In
57
Acute

an angiotensin-II receptor antagonist), a beta-

with heart failure.[164] [166]
» There have been no long-term studies of

diuretic therapy in heart failure; therefore, their
effects on morbidity and mortality are not known.

Primary options
OR

MANAGEMENT

Acute
unless contraindicated.[2]




adjunct digoxin
Primary options


MANAGEMENT

59
Acute
» Digoxin reduces the composite end point of
mortality or hospitalisations, but does not reduce
all-cause mortality.[121] One meta-analysis
suggests that digoxin use in patients with heart
failure is associated with a higher risk of all-
cause mortality.[122]

exists.[173] [174]



adjunct ivabradine
Primary options

heart rate

take beta-blockers.


MANAGEMENT

Acute
Primary options


symptoms.[2] [127]
MANAGEMENT
61
Ongoing
refractory to optimal medical
treatment
LVEF <35%: no left 1st implantable cardioverter-defibrillator (ICD)

bundle-branch block
» An ICD is recommended in the following
cases:[2]
» 1) For primary prevention of sudden cardiac

death in selected patients with both non-
ischaemic and ischaemic heart failure, at least
40 days post myocardial infarction, LVEF <35%,
New York Heart Association (NYHA) class II
or III symptoms on guideline-directed medical
therapy, and expected to live for >1 year, or
LVEF <30%, NHYA class I, on guideline-directed
medical therapy, and expected to live for >1 year.
» 2) As secondary prevention to prolong survival

in patients with current or prior symptoms
of heart failure and reduced left ventricular
ejection fraction (LVEF) who have a history
of cardiac arrest, ventricular fibrillation, or
haemodynamically destabilising ventricular
tachycardia.
» Patients with refractory end-stage disease

who already carry an ICD may want to receive
information about the option to inactivate
defibrillation.
2nd mechanical circulatory support
» Mechanical circulatory support, which includes

ventricular assist devices, helps to maintain
sufficient end organ perfusion by unloading the
heart and is considered in carefully selected
patients who have end-stage heart failure,
despite optimal medical and device therapy,
and in whom definite management (e.g.,
cardiac transplantation) or cardiac recovery is
anticipated.[1] [2]
» Currently in the US, the accepted

indications for implantation of a durable left
ventricular assist device (LVAD) are bridge
to transplantation and destination therapy
(permanent pump implantation in patients not
eligible for cardiac transplantation).[158] In
clinical practice, another indication for LVAD is to
provide a bridge to decisions about future care.
MANAGEMENT
» The European Society of Cardiology has

outlined the various indications for mechanical
circulatory support:[1]
Ongoing
» 1) Bridge to decision/bridge to bridge: use
of short-term support (e.g., extracorporeal life
support [ECLS] or extracorporeal membrane
oxygenation [ECMO] in patients with cardiogenic
shock until haemodynamics and end-organ
perfusion are stabilised, contraindications for
long-term support are excluded, and therapeutic
options including long-term VAD therapy or heart
transplant can be evaluated.
» 2) Bridge to candidacy: use of support (usually

LVAD) to make ineligible patient eligible for heart
transplant.
» 3) Bridge to transplantation: use of LVAD or

biventricular assist device to keep high-risk
transplant candidate alive until donor organ
becomes available.
» 4) Bridge to recovery: use of support (usually

LVAD) to keep the patient alive until cardiac
function recovers sufficiently to remove it.
» 5) Destination therapy: long-term use of LVAD

as alternative to heart transplant.
» Some of the absolute contraindications for

providing durable mechanical support include
irreversible hepatic, renal and neurological
disease, medical non-adherence, and severe
psychosocial limitations.[159]
» Cardiac transplantation is an option for

refractory end-stage disease. Before a patient
is considered to have refractory end-stage
disease, the accuracy of the diagnosis should be
confirmed, any contributing conditions should be
identified, and all conventional medical strategies
should have been optimally employed.
LVEF <35%: left bundle- 1st cardiac re-synchronisation therapy with
branch block biventricular pacemaker (CRT-P)/cardiac
resynchronisation therapy-defibrillator
(CRT-D)
» In patients with left ventricular (LV) systolic

dysfunction and dyssynchronous ventricular
activation, cardiac pacing provides simultaneous
and coordinated electrical activation of both
the left and right ventricle. This cardiac
resynchronisation therapy (CRT) is provided
MANAGEMENT
either by a CRT-pacemaker (CRT-P) or by

a combined CRT-implantable cardioverter-
defibrillator (CRT-D).
» The CRT-P prevents deterioration in LV

function by correcting the LV dyssynchrony and
63
Ongoing
the CRT-D prevents sudden cardiac death from
ventricular arrhythmias.
» As both CRT-P and CRT-D are indicated

in patients with heart failure and low ejection
fraction, there is considerable overlap in the
indications for the use of these devices.
» Long-term data from the REVERSE study

suggest that improvements in left ventricular
function and remodelling can be sustained for
over 5 years.[155] [156]
» CRT decreases hospitalisation and, when

combined with an ICD, significantly reduces
mortality.[134] [135] [136] [137] [138] [139]
» In patients who have conduction delay and left

ventricular dysfunction, biventricular pacemakers
have been shown to improve exercise tolerance
and quality of life while decreasing morbidity and
mortality.[134] [135] [136] [137] [139] [140] [141]
[142]
» CRT is indicated in patients with LVEF ≤35%,

sinus rhythm, LBBB with QRS ≥150 ms, and
NYHA class II, III or ambulatory NYHA IV on
guideline-directed medical therapy.[2]
» Recommendations for the use of CRT

devices in heart failure are detailed in the 2013
American College of Cardiology/American Heart
Association guidelines.[2]
2nd left ventricular assist device (LVAD)
» Mechanical circulatory support, which includes

ventricular assist devices, helps to maintain
sufficient end organ perfusion by unloading the
heart and is considered in carefully selected
patients who have end-stage heart failure,
despite optimal medical and device therapy,
and in whom definite management (e.g.,
cardiac transplantation) or cardiac recovery is
anticipated.[1] [2]
» Currently in the US, the accepted

indications for implantation of a durable left
ventricular assist device (LVAD) are bridge
to transplantation and destination therapy
(permanent pump implantation in patients not
eligible for cardiac transplantation).[158] In
clinical practice, another indication for LVAD is to
MANAGEMENT
provide a bridge to decisions about future care.
» The European Society of Cardiology has

outlined the various indications for mechanical
circulatory support:[1]
Ongoing
» 1) Bridge to decision/bridge to bridge: use
of short-term support (e.g., extracorporeal life
support [ECLS] or extracorporeal membrane
oxygenation [ECMO] in patients with cardiogenic
shock until haemodynamics and end-organ
perfusion are stabilised, contraindications for
long-term support are excluded, and therapeutic
options including long-term VAD therapy or heart
transplant can be evaluated.
» 2) Bridge to candidacy: use of support (usually

LVAD) to make ineligible patient eligible for heart
transplant.
» 3) Bridge to transplantation: use of LVAD or

biventricular assist device to keep high-risk
transplant candidate alive until donor organ
becomes available.
» 4) Bridge to recovery: use of support (usually

LVAD) to keep the patient alive until cardiac
function recovers sufficiently to remove it.
» 5) Destination therapy: long-term use of LVAD

as alternative to heart transplant.
» Some of the absolute contraindications for

providing durable mechanical support include
irreversible hepatic, renal and neurological
disease, medical non-adherence, and severe
psychosocial limitations.[159]
» Cardiac transplantation is an option for

refractory end-stage disease. Before a patient
is considered to have refractory end-stage
disease, the accuracy of the diagnosis should be
confirmed, any contributing conditions should be
identified, and all conventional medical strategies
should have been optimally employed.
MANAGEMENT
65
Emerging
Calcium-sensitising agents
Levosimendan, a novel calcium sensitiser, improves myocardial contractility without causing an increase
in myocardial oxygen demand. Its role in acute, decompensated heart failure is more established than
in chronic heart failure, but it may reduce overall mortality and time in hospital.[178] In the LIDO study,
levosimendan improved survival and haemodynamic performance more effectively than dobutamine, in
patients with severe, low-output heart failure.[179] The superiority of levosimendan over dobutamine in
improving central haemodynamics and left ventricular performance seems in part to be related to its anti-
inflammatory and anti-apoptotic effects.[180]
n-3 polyunsaturated fat ty acids (n3-PUFA)

The GISSI-HF trial showed that the addition of n3-PUFA produced a small improvement in mortality and
hospital admissions in patients with heart failure.[181] However, a 2012 meta-analysis has shown insufficient
evidence of a secondary preventive effect of omega-3 fatty acid supplements against overall cardiovascular
events among patients with a history of cardiovascular disease.[182] Omega-3 PUFA supplementation is
reasonable to use as adjunctive therapy in patients with New York Heart Association class II to IV symptoms
and heart failure, unless contraindicated, to reduce mortality and cardiovascular hospitalisations.
Statins
Statins are not beneficial as adjunctive therapy when prescribed solely for treatment of heart failure in the
absence of other indications for their use.[2] Statin therapy has been broadly implicated in prevention of
adverse cardiovascular events, including new-onset heart failure. Originally designed to lower cholesterol in
patients with cardiovascular disease, statins are known to have beneficial effects on inflammation, oxidative
stress, and vascular performance. To date, a sufficient body of evidence does not exist to support the
primary prescribing of statins for the treatment of heart failure to improve clinical outcomes.[2]
Non-specific immunomodulation therapy

Inflammatory mediators are proposed to play a role in heart failure development and progression. In
the ACCLAIM trial, non-specific immunomodulation therapy reduced the risk of hospitalisation or death,
suggesting that this therapy may be of benefit in heart failure patients.[183]
Recombinant human growth hormone

Preliminary studies suggest that recombinant human growth hormone may have beneficial effects in patients
with left ventricular dysfunction, although it may produce an increased risk of arrhythmias.[184] [185] Further
studies are required to determine the safety and efficacy of this treatment.
Trimeta zidine
In a meta-analysis, trimetazidine, which shifts energy production from fatty acid oxidation to glucose
oxidation, was shown to have no effect on mortality, but it improves left ventricular ejection fraction (LVEF)
and functional class.[186]
Sodium–glucose cotransporter 2 (SGLT2) inhibitors

SGLT2 inhibitors have been investigated for patients with heart failure with and without diabetes. In a phase
MANAGEMENT
3 randomised controlled trial, dapagliflozin was found to reduce the risk of worsening heart failure or death
from cardiovascular causes compared with placebo in patients with heart failure and reduced ejection
fraction, regardless of whether the patient also had diabetes.[187] The US Food and Drug Administration
(FDA) has approved dapagliflozin for adults with heart failure with reduced ejection fraction to reduce the
risk of cardiovascular death and hospitalisation. In Europe, dapagliflozin and empagliflozin are approved for
the treatment of adults with symptomatic chronic heart failure with reduced ejection fraction. Empagliflozin
has been granted fast track designation by the FDA for the reduction of risk for cardiovascular death and
hospitalisation for heart failure in people with chronic heart failure.
Vericiguat
The US Food and Drug Administration has approved vericiguat, an orally administered soluble guanylate
cyclase stimulator, for treatment of chronic heart failure in patients who are hospitalised for heart failure or
need outpatient intravenous diuretics. In Europe, vericiguat is approved for the treatment of symptomatic
chronic heart failure in adult patients with reduced ejection fraction who are stabilised after a recent
decompensation event requiring intravenous therapy.
Novel implantable devices

Cardiac contractility modulation (CCM) delivers non-excitatory electrical stimulation to the ventricle during the
absolute refractory period to enhance contractile performance without activating extra systolic contractions.
CCM works via key calcium regulatory pathways that increase cardiac contractility.[188] The Optimizer
Smart system is an implantable pulse generator that delivers CCM therapy and has been approved by the
US FDA for the treatment of patients with chronic, moderate-to-severe heart failure who are not suited for
treatment with other heart failure devices such as cardiac resynchronisation therapy to restore a normal
timing pattern of the heartbeat. The Barostim Neo System is an implantable device that delivers baroreflex
activation therapy (BAT); it has been approved by the FDA for the improvement of symptoms in patients with
advanced heart failure who are not suited for treatment with other heart failure devices, such as cardiac
resynchronisation therapy. In patients with New York Heart Association functional class III heart failure and
ejection fraction <35% on chronic stable guideline-directed medical therapy, use of BAT has been shown
to improve functional status, quality of life, exercise capacity, and N-terminal pro–brain natriuretic peptide
levels.[189]
Stem-cell therapy
Some trials of stem-cell therapy in both ischaemic and non-ischaemic heart failure have shown some
potential benefit.[190] A systematic review on the use of stem-cell therapy for chronic ischaemic heart
disease and congestive heart failure suggests that at both short- and long-term follow-up (≥12 months)
the use of autologous bone marrow stem-cell treatment reduces all-cause mortality, although the quality of
evidence is low.[191]
Gene therapy
An attractive strategy for treatment of heart failure is by gene therapy.[192] In a small randomised study of
patients (n=56) with heart failure and LVEF <40%, intracoronary delivery of adenovirus 5 encoding adenylyl
cyclase 6 (Ad5.hAC6), increased the LVEF at 4 weeks, with no increase in exercise duration.[193] In a larger
double-blind placebo-controlled study (n=250), intracoronary infusion of 1 × 1013 DNase-resistant particle
of adeno-associated virus 1 (AAV1) / sarcoplasmic endoplasmic reticulum Ca2-ATPase (SERCA2a) did
not improve the clinical course of patients with heart failure and reduced ejection fraction (ejection fraction
≤35%).[194]
Surgical strategies
There have been numerous reports of alternate surgical approaches for the treatment of end-stage heart
failure.[195] Mitral valve repair or replacement has been shown to improve clinical status in patients who
have a clinically important degree of mitral regurgitation that is secondary to left ventricular dilation.[196]
However, no controlled studies have evaluated the effects of this procedure on ventricular function,
MANAGEMENT
re-hospitalisations, or survival. One single-centre study designed to assess the effects of mitral valve
annuloplasty on mortality in patients with mitral regurgitation and left ventricular systolic dysfunction failed
to demonstrate any clear survival benefit.[197] A variant of the aneurysmectomy procedure is now being
developed for the management of patients with ischaemic cardiomyopathy, but its role in the management of
heart failure remains to be defined.[198] None of the current surgical reconstruction techniques offer 'rescue
therapy' to patients with critical haemodynamic compromise.
67
Intravenous iron
In patients with iron deficiency and systolic heart failure, treatment with intravenous ferric carboxymaltose
has been associated with lower rates of recurrent cardiovascular hospitalisations and mortality.[199]
Primary prevention
Heart failure is the final pathway for a wide array of pathophysiological processes. Interventions that reduce
the risk of development of any cardiovascular disease will ultimately reduce the incidence of heart failure.[76]
Thus, key public health targets are prevention of development of hypertension, diabetes, dyslipidaemia,
obesity (i.e., metabolic syndrome), and ischaemic heart disease. Lifestyle modifications, such as increasing
physical activity, reducing tobacco, alcohol, and recreational drug use, and reducing daily salt intake, and
proper medical treatment of established diseases such as hypertension, diabetes, and coronary artery
disease, are expected to help reduce incident heart failure.[76] [77] [78]
Patient discussions
On discharge from hospital, patients should be instructed on:
• Daily home weight monitoring

• Sodium restriction (2 g to 3 g daily) and fluid restriction when necessary
• Tobacco and alcohol discontinuation
• Aggressive control of hypertension and diabetes (e.g., provide patients with blood pressure and
HbA1c goal)
• Lipid management (e.g., provide leaflets and show website links for diet, exercise, and healthy
lifestyle)
• Regular, symptom-limited exercise
• Routine health-care maintenance.
MANAGEMENT
Chronic congestive heart failure Follow up
Monitoring
Monitoring
FOLLOW UP
Patients benefit from frequent formal evaluation in a specialised centre or monitoring in a management
programme.[229] Assessment should be made at each visit of the ability of a patient to perform routine
and desired activities of daily living. Assessment should be also made of the fluid status and weight
of the patient. Careful history of current use of alcohol, tobacco, illicit drugs, alternative therapies,
and chemotherapy drugs, as well as diet and sodium intake, should be obtained at each visit. Repeat
measurement of ejection fraction and assessment of the severity of structural remodelling can provide
useful information in patients with heart failure who have had a change in clinical status, or who have
experienced or recovered from a clinical event, or received treatment that might have had a significant
effect on cardiac function. The value of serial measurements of B-type natriuretic peptide to guide
therapy for patients is still not well established. Data suggest that natriuretic-guided therapy reduces
hospitalisation due to heart failure and that in patients younger than 75 years of age, it also provides a
survival benefit.[230] However, one randomised trial found that in high-risk patients with heart failure,
natriuretic-guided therapy was not more effective than optimal medical therapy alone in improving
outcomes.[231] The use of telemonitoring to monitor patients remotely is an emerging strategy but
requires further evaluation.[232] [233] [Evidence A]
Wireless pulmonary haemodynamic monitoring in patients with chronic heart failure results in significant
reduction in heart failure hospitalisations.[234]
Structured telephone support and non-invasive home telemonitoring can reduce the risk of mortality and
heart failure-related hospitalisations.[235]
Invasive haemodynamic monitoring, however, is not routinely used in clinical practice, but may be of use
in individual patients, particularly those with recurrent heart failure.
In one study of patients with New York Heart Association class III heart failure, wireless implantable
haemodynamic monitoring compared with control led to a significant reduction of heart failure-related
hospitalisations.[234]
Exercise training and rehabilitation
• In patients with heart failure, cardiac rehabilitation and exercise training improves exercise
tolerance and quality of life with decreased morbidity and mortality.[236] Patients with stable heart
failure are therefore encouraged to do regular aerobic exercise and it is recommended that they are
enrolled in a multidisciplinary care management programme.[237] One consensus paper provides a
detailed description of exercise training in heart failure.[238]
69
Complications
Complications Timeframe Likelihood

FOLLOW UP
pleural effusion long term high
Pleural effusions are a common complication of chronic congestive heart failure.
chronic kidney disease long term medium
A common reason for refractory symptoms is the cardiorenal syndrome, a spectrum of disorders involving
the heart and kidneys in which acute or chronic dysfunction in one organ may induce acute or chronic
dysfunction in the other organ.[211] These patients show an impaired response to diuretics and ACE
inhibitors and are at increased risk of adverse effects during treatment with digoxin.[212] [213] [214]
Persistent or progressive renal functional impairment has been associated with a poor prognosis.[215]
[216] The symptoms of heart failure in patients with end-stage renal disease may be exacerbated
by an increase in loading conditions produced both by anaemia and by fistulas implanted to permit
dialysis.[217] Most patients will tolerate mild-to-moderate degrees of functional renal impairment without
difficulty. However, if the serum creatinine increases to more than 265 micromols/L (>3 mg/dL), the renal
insufficiency can severely limit the efficacy and enhance the toxicity of established treatments.[212] [218]
Impaired renal function may exclude the therapeutic use of ACE inhibitors and angiotensin-II receptor
antagonists. In patients with a serum creatinine greater than 442 micromols/L (>5 mg/dL), haemofiltration
or dialysis may be needed to control fluid retention, minimise the risk of uraemia, and allow the patient to
respond to and tolerate the drugs routinely used for the management of heart failure.[219] [220] [221] [222]
anaemia long term medium
Patients with heart failure frequently have anaemia for a variety of reasons, which may worsen heart
failure symptoms. Several studies have demonstrated worse outcomes in patients with heart failure
and anaemia, such as a 1.027 higher risk for mortality associated with a 1% lower haematocrit, after
adjustment for other factors.[223] [224] It is unclear whether anaemia is the cause of decreased
survival or a marker of more severe disease. Several small studies have suggested benefit from use of
erythropoietin and iron for treatment of mild anaemia in heart failure, although at the cost of increased
risk of thromboembolic events.[225] [226] [227] However, a larger study showed no clinical benefit of
darbepoietin alfa treatment.[228]
acute decompensation of chronic heart failure variable high
Despite optimal treatment, many precipitating factors or even new events may cause acute
decompensation of a previously stable patient, thus leading to pulmonary oedema (backward failure) or
cardiogenic shock (forward failure). Common causes include myocardial infarction and its mechanical
complications (papillary muscle rupture with new-onset acute mitral regurgitation, ventricular septal defect,
and ventricular rupture), arrhythmias, pulmonary embolism, infection, anaemia, tamponade, myocarditis,
acute renal failure or even increased salt intake, inappropriate drug therapy, or patient non-compliance.
Patients with acute decompensation require urgent haemodynamic stabilisation and diagnosis of the
precipitating cause. Pharmacological therapy includes intravenous diuretics, intravenous positive inotropic
agents, intravenous vasodilators, and intravenous vasopressors. Non-pharmacological treatment
modalities will be necessary - these include oxygenation, balloon counterpulsation, pacing, urgent
catheterisation or urgent cardiac surgery, or mechanical support with ventricular assist devices.
acute kidney injury variable high
Complications Timeframe Likelihood

Patients have a high risk of developing acute renal insufficiency at any point of their clinical course as
FOLLOW UP
a result of either poor renal perfusion (low cardiac output state) or drug overuse to treat heart failure
(diuretics, ACE inhibitors, aldosterone antagonists, angiotensin-II receptor antagonists). In addition, the
use of carvedilol requires close monitoring of the renal function as it could contribute, with other agents, to
the development of acute renal injury. Inability to maintain adequate renal perfusion on oral therapy may
eventually necessitate IV inotropic infusion or urgent ultrafiltration and haemodialysis.
sudden cardiac death variable medium
Sudden cardiac death is common in heart failure patients and accounts for approximately 30% to
40% of the deaths among these patients. It can be the consequence of both ventricular fibrillation
and electromechanical dissociation, and can occur any time in the course of the disease, even in the
asymptomatic patient.
In patients who survive an episode of cardiac arrest, prophylactic insertion of an implantable cardioverter
defibrillator and initiation of appropriate anti-arrhythmic therapy is indicated.
Prognosis
The evaluation of a patient would be incomplete without an initial and periodic assessment of short- and
long-term prognosis. However, the likelihood of survival can be determined reliably only in populations
and not in individual patients. Numerous factors have been used as prognostic indicators, including
demographics (age, sex, race), symptoms (New York Heart Association [NYHA] classification), comorbidities
(hypertension, diabetes, cachexia, anaemia, and renal and hepatic dysfunction), and objective clinical
parameters (e.g., ejection fraction, left ventricular size, volume, mass and shape, exercise capacity,
and serum levels of sodium, noradrenaline [norepinephrine], renin, B-type natriuretic peptide, uric acid,
angiotensin II, aldosterone, tumour necrosis factor-alpha, endothelin). Multi-variate analysis of these
variables has helped to identify the most significant predictors of survival, and prognostic models have
been developed and validated.[200] [201] [202] [203] [204] [205] [206] [207] However, all existing models
to predict the risk of death or need for urgent transplantation have features that may limit their applicability.
Haemoglobin A1c was also found to be an independent progressive risk factor for cardiovascular death,
hospitalisation, and mortality, even in non-diabetic patients.[208]
The most comprehensive prognostic model is the Seattle Heart Failure Model. [The Seattle Heart Failure
Model] (http://depts.washington.edu/shfm) This model has been implemented as an interactive programme
that employs the Seattle Heart Failure Score to estimate mean, 1-, 2-, and 5-year survival and the benefit of
adding medicines and/or devices for an individual patient.[202]
Despite standard medical therapy the survival for patients with end-stage heart failure is poor.
Despite optimal medical therapy including cardiac re-synchronisation therapy, only 65% of patients in NYHA
class 4 are alive at a mean follow-up of 17 months.[209]
The 5-year survival in patients with stage D heart failure is only 20%.[210]
71
Chronic congestive heart failure Guidelines
Diagnostic guidelines
United Kingdom
Chronic heart failure in adults: diagnosis and management (ht tps://

www.nice.org.uk/guidance/ng106)
Published by: National Institute for Health and Care Excellence Last published: 2018
Management of chronic heart failure (ht tps://www.sign.ac.uk/our-

guidelines.html)
Published by: Scottish Intercollegiate Guidelines Network Last published: 2016
Europe
2016 ESC guidelines for the diagnosis and treatment of acute and chronic
GUIDELINES
heart failure (ht tps://www.escardio.org/Guidelines/Clinical-Practice-

Guidelines)
Published by: European Society of Cardiology Last published: 2016
North America
2017 comprehensive update of the Canadian Cardiovascular Society

guidelines for the management of heart failure (ht tp://www.ccs.ca/index.php/
en/guidelines/guidelines-library)
Published by: Canadian Cardiovascular Society Last published: 2017
2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the
management of heart failure (ht tps://professional.heart.org/professional/
GuidelinesStatements/UCM_316885_Guidelines-Statements.jsp)
Published by: American College of Cardiology; American Heart Last published: 2017
Association; Heart Failure Society of America
2013 ACCF/AHA guideline for the management of heart failure

(ht tps://professional.heart.org/professional/GuidelinesStatements/
UCM_316885_Guidelines-Statements.jsp)
Published by: American College of Cardiology Foundation; American Last published: 2013
Heart Association
Oceania
Guidelines for the prevention, detection, and management of heart failure

in Australia (ht tps://www.heart foundation.org.au/for-professionals/clinical-
information/heart-failure)
Published by: National Heart Foundation of Australia; Cardiac Society Last published: 2018
of Australia and New Zealand
Treatment guidelines
United Kingdom
Chronic heart failure in adults: diagnosis and management (ht tps://

www.nice.org.uk/guidance/ng106)
Cardiac arrythmias in coronary heart disease (ht tps://www.sign.ac.uk/our-

guidelines.html)
Management of chronic heart failure (ht tps://www.sign.ac.uk/our-

guidelines.html)
GUIDELINES
Implantable cardioverter defibrillators and cardiac resynchronisation therapy

for arrhythmias and heart failure (ht tps://www.nice.org.uk/Guidance/TA314)
Europe
Advanced heart failure: a position statement of the Heart Failure Association

of the European Society of Cardiology (ht tps://www.escardio.org/Guidelines/
Consensus-and-Position-Papers/heart-failure)
2016 ESC guidelines for the diagnosis and treatment of acute and chronic
heart failure (ht tps://www.escardio.org/Guidelines/Clinical-Practice-
Guidelines)
European Resuscitation Council guidelines 2021 (ht tps://cprguidelines.eu)

Published by: European Resuscitation Council Last published: 2021
73
North America
CCS/CHFS heart failure guidelines: clinical trial update on functional mitral

regurgitation, SGLT2 inhibitors, ARNI in HFpEF, and tafamidis in amyloidosis
(ht tps://ccs.ca/guidelines-and-position-statement-library)
Home-based cardiac rehabilitation (ht tps://professional.heart.org/en/

guidelines-and-statements)
Published by: American Association of Cardiovascular and Pulmonary Last published: 2019
Rehabilitation, American Heart Association, American College of
Cardiology
Device therapy and arrhythmia management in left ventricular assist device

recipients (ht tps://professional.heart.org/en/guidelines-and-statements)
Published by: American Heart Association Last published: 2019
GUIDELINES
Evaluation and management of right-sided heart failure (ht tps://

professional.heart.org/en/guidelines-and-statements)
Published by: American Heart Association Last published: 2018
Physical activity guidelines for Americans (ht tps://health.gov/paguidelines)

Published by: US Department of Health and Human Services Last published: 2018
2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the
management of heart failure (ht tps://professional.heart.org/professional/
GuidelinesStatements/UCM_316885_Guidelines-Statements.jsp)
Published by: American College of Cardiology; American Heart Last published: 2017
Association; Heart Failure Society of America
ACC/AATS/AHA/ASE/ASNC/SCAI/SCCT/STS 2017 appropriate use criteria for

coronary revascularization in patients with stable ischemic heart disease
(ht tps://www.acc.org/guidelines#tab4)
Published by: American College of Cardiology; American Association Last published: 2017
for Thoracic Surgery; American Heart Association; American Society of
Echocardiography; American Society of Nuclear Cardiology; Society for
Cardiovascular Angiography and Interventions; Society of Cardiovascular
Computed Tomography; Society of Thoracic Surgeons
2017 comprehensive update of the Canadian Cardiovascular Society

guidelines for the management of heart failure (ht tp://www.ccs.ca/index.php/
en/guidelines/guidelines-library)
Heart failure evidence-based nutrition practice guideline (ht tps://

www.andeal.org/topic.cfm?menu=5289)
Published by: Academy of Nutrition and Dietetics Last published: 2017
North America
ACC/AATS/AHA/ASE/ASNC/SCAI/SCCT/STS 2016 appropriate use criteria

for coronary revascularization in patients with acute coronary syndromes
(ht tps://www.acc.org/guidelines#tab4)
Published by: American College of Cardiology; American Association Last published: 2016
for Thoracic Surgery; American Heart Association; American Society of
Echocardiography; American Society of Nuclear Cardiology; Society for
Cardiovascular Angiography and Interventions; Society of Cardiovascular
Computed Tomography; Society of Thoracic Surgeons
Chronic heart failure - diagnosis and management (ht tps://www2.gov.bc.ca/

gov/content/health/practitioner-professional-resources/bc-guidelines/
guidelines-by-alphabetical-listing)
Published by: British Columbia Medical Association Last published: 2015
2013 ACCF/AHA guideline for the management of heart failure
GUIDELINES
Heart Association
2012 ACCF/AHA/HRS focused update incorporated into the ACCF/AHA/HRS

2008 guidelines for device-based therapy of cardiac rhythm abnormalities
Heart Association
Task force 8: training in heart failure (ht tp://www.onlinejacc.org/

content/51/3/383)
Published by: Heart Failure Society of America Last published: 2008
Oceania
Guidelines for the prevention, detection, and management of heart failure in

Australia (ht tps://www.heart foundation.org.au/Conditions/Heart-failure-for-
professionals)
Published by: National Heart Foundation of Australia; Cardiac Society Last published: 2018
of Australia and New Zealand
75
Chronic congestive heart failure Online resources
Online resources
1. The Seattle Heart Failure Model (http://depts.washington.edu/shfm) (external link)
ONLINE RESOURCES
Chronic congestive heart failure Evidence tables
Evidence tables
In people with heart failure, what are the effects of interactive telemedicine?
EVIDENCE TABLES
This table is a summary of the analysis reported in a Cochrane Clinical Answer that focuses on the
above important clinical question.
View the full source Cochrane Clinical Answer (https://www.cochranelibrary.com/cca/

doi/10.1002/cca.1311/full)
Evidence A * Confidence in the evidence is high or moderate to high where GRADE has been
performed and there is no difference in effectiveness between the intervention and
comparison for key outcomes.
Population: Adults (mean age 53 to 79 years) with heart failure

Intervention: Telemedicine (includes remote monitoring with system for alerting healthcare professionals,
automatic clinical review of data, and/or videoconferencing for patient assessment and self-management
education and support) with or without usual care
Comparison: Usual care (where reported: home nursing visits or pharmacological treatment)
† ‡
Outcome Effectiveness (BMJ rating) Confidence in evidence (GRADE)
All‐cause mortality at median 6 No statistically significant High

months’ follow‐up ᵃ difference
Disease‐specific quality of life Favours intervention Moderate

at median 3 months’ follow‐up
All‐cause hospital admissions Unknown ᵇ Moderate

at median 8 months’ follow‐up:
monitoring with clinical review
of data
All‐cause hospital admissions Unknown ᶜ Moderate

at median 8 months’ follow‐up:
monitoring with alerts
Heart failure and/or Unknown ᵈ GRADE assessment not performed for

cardiovascular‐related this outcome
admissions at 3-12 months’
follow‐up
Emergency department and No statistically significant GRADE assessment not performed for
urgent care visits at median 4 difference this outcome
months’ follow‐up
77
† ‡
Outcome Effectiveness (BMJ rating) Confidence in evidence (GRADE)
Length of stay at median 6 No statistically significant GRADE assessment not performed for
EVIDENCE TABLES
months’ follow‐up difference this outcome
Length of stay related to heart No statistically significant GRADE assessment not performed for
failure at median 6 months’ difference this outcome
follow‐up
Adverse effects - None of the studies identified by the

review assessed this outcome
Note
ᵃ The Cochrane Clinical Answer (CCA) notes that there was a reduction in mortality with telemedicine that did
not quite meet statistical significance.
ᵇ Results reported narratively (2 RCTs with 156 people; 1 favoured telemedicine while the other reported no
statistically significant difference between treatment groups).
ᶜ Results reported narratively (9 RCTs with 4373 people, all of which reported no statistically significant
difference between treatment groups, apart from 1 which favoured telemedicine).
ᵈ Results reported narratively (16 studies with 3236 people, 3 of which reported a reduction in heart failure
and/or cardiovascular-related admissions with telemedicine, while the other studies reported similar rates of
admission between treatment groups).
* Evidence levels
The Evidence level is an internal rating applied by BMJ Best Practice. See the EBM Toolkit (https://
bestpractice.bmj.com/info/evidence-tables/) for details.
Confidence in evidence
A - High or moderate to high

B - Moderate or low to moderate
C - Very low or low
† Effectiveness (BMJ rating)

Based on statistical significance, which demonstrates that the results are unlikely to be due to chance, but
which does not necessarily translate to a clinical significance.
‡ Grade certainty ratings
High The authors are very confident that the true

effect is similar to the estimated effect.
EVIDENCE TABLES
Moderate The authors are moderately confident that
the true effect is likely to be close to the
estimated effect.
Low The authors have limited confidence in the
effect estimate and the true effect may be
substantially different.
Very Low The authors have very little confidence in
the effect estimate and the true effect is
likely to be substantially different.
BMJ Best Practice EBM Toolkit: What is GRADE? (https://bestpractice.bmj.com/info/toolkit/learn-ebm/what-
is-grade/)
79
Chronic congestive heart failure References
Key articles
• Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC guidelines for the diagnosis and treatment
REFERENCES
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). Eur J Heart Fail. 2016
Aug;18(8):891-975. Full text (https://onlinelibrary.wiley.com/doi/full/10.1002/ejhf.592) Abstract (http://
www.ncbi.nlm.nih.gov/pubmed/27207191?tool=bestpractice.bmj.com)
• 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. J Am Coll Cardiol. 2013 Oct 15;62(16):e147-239. Full text (https://www.jacc.org/
doi/full/10.1016/j.jacc.2013.05.019) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/23747642?
tool=bestpractice.bmj.com)
• McKee PA, Castelli WP, McNamara PM, et al. The natural history of congestive heart failure: the
Framingham study. N Engl J Med. 1971 Dec 23;285(26):1441-6. Abstract (http://www.ncbi.nlm.nih.gov/
pubmed/5122894?tool=bestpractice.bmj.com)
• Groenewegen A, Rutten FH, Mosterd A, et al. Epidemiology of heart failure. Eur J Heart Fail.
2020 Aug;22(8):1342-56. Full text (https://www.doi.org/10.1002/ejhf.1858) Abstract (http://
• National Institute for Health and Care Excellence. Chronic heart failure in adults: diagnosis and
management. Sep 2018 [internet publication]. Full text (https://www.nice.org.uk/guidance/ng106)
• Levy D, Larson MG, Vasan RS, et al. The progression from hypertension to congestive heart failure.
JAMA. 1996 May 22-29;275(20):1557-62. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/8622246?
• Wang TJ, Larson MG, Levy D, et al. Plasma natriuretic peptide levels and the risk of cardiovascular
events and death. N Engl J Med. 2004 Feb 12;350(7):655-63. Full text (https://www.nejm.org/
doi/full/10.1056/NEJMoa031994) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/14960742?
• Mehra MR, Canter CE, Hannan MM, et al. The 2016 International Society for Heart Lung
Transplantation listing criteria for heart transplantation: a 10-year update. J Heart Lung
Transplant. 2016 Jan;35(1):1-23. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/26776864?
• Cleland JG, Daubert JC, Erdmann E, et al. The effect of cardiac resynchronization on morbidity and
mortality in heart failure. N Engl J Med. 2005 Apr 14;352(15):1539-49. Full text (https://www.nejm.org/
doi/10.1056/NEJMoa050496) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/15753115?
• Levy WC, Mozaffarian D, Linker DT, et al. The Seattle Heart Failure Model: prediction of survival in
heart failure. Circulation. 2006 Mar 21;113(11):1424-33. Full text (https://www.ahajournals.org/doi/
full/10.1161/circulationaha.105.584102) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/16534009?
REFERENCES
• 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. J Am Coll Cardiol. 2013 Oct 15;62(16):e147-239. Full text (http://
www.onlinejacc.org/content/62/16/e147) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/23747642?
• Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC guidelines for the diagnosis and treatment
References
1. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC guidelines for the diagnosis and treatment
2. 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. J Am Coll Cardiol. 2013 Oct 15;62(16):e147-239. Full text (https://www.jacc.org/
doi/full/10.1016/j.jacc.2013.05.019) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/23747642?
3. McKee PA, Castelli WP, McNamara PM, et al. The natural history of congestive heart failure: the
Framingham study. N Engl J Med. 1971 Dec 23;285(26):1441-6. Abstract (http://www.ncbi.nlm.nih.gov/
4. Groenewegen A, Rutten FH, Mosterd A, et al. Epidemiology of heart failure. Eur J Heart Fail.
2020 Aug;22(8):1342-56. Full text (https://www.doi.org/10.1002/ejhf.1858) Abstract (http://
5. Savarese G, Lund LH. Global public health burden of heart failure. Card Fail Rev. 2017
Apr;3(1):7-11. Full text (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5494150) Abstract (http://
6. Sahle BW, Owen AJ, Mutowo MP, et al. Prevalence of heart failure in Australia: a systematic
review. BMC Cardiovasc Disord. 2016 Feb 6;16:32. Full text (https://www.doi.org/10.1186/
s12872-016-0208-4) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/26852410?
81
7. National Institute for Health and Care Excellence. Chronic heart failure in adults: diagnosis and
management. Sep 2018 [internet publication]. Full text (https://www.nice.org.uk/guidance/ng106)
REFERENCES
8. Virani SS, Alonso A, Benjamin EJ, et al. Heart disease and stroke statistics - 2020 update: a
report from the American Heart Association. Circulation. 2020 Mar 3;141(9):e139-e596. Full text
(https://www.doi.org/10.1161/CIR.0000000000000757) Abstract (http://www.ncbi.nlm.nih.gov/
9. O'Connell JB, Bristow MR. Economic impact of heart failure in the United States: time for a
different approach. J Heart Lung Transplant. 1994 Jul-Aug;13(4):S107-12. Abstract (http://
10. O'Connell JB. The economic burden of heart failure. Clin Cardiol. 2000 Mar;23(3 Suppl):III6-10.
Abstract (http://www.ncbi.nlm.nih.gov/pubmed/10754775?tool=bestpractice.bmj.com)
11. Koelling TM, Chen RS, Lubwama RN, et al. The expanding national burden of heart failure in the
United States: the influence of heart failure in women. Am Heart J. 2004 Jan;147(1):74-8. Abstract
(http://www.ncbi.nlm.nih.gov/pubmed/14691422?tool=bestpractice.bmj.com)
12. Abhayaratna WP, Smith WT, Becker NG, et al. Prevalence of heart failure and systolic ventricular
dysfunction in older Australians: the Canberra Heart Study. Med J Aust. 2006 Feb 20;184(4):151-4.
13. Kloner RA. Stunned and hibernating myocardium: where are we nearly 4 decades later? J Am Heart
Assoc. 2020 Feb 4;9(3):e015502. Full text (https://www.doi.org/10.1161/JAHA.119.015502) Abstract
14. Patel H, Madanieh R, Kosmas CE, et al. Reversible cardiomyopathies. Clin Med Insights Cardiol.
2015;9(suppl 2):7-14. Full text (https://www.doi.org/10.4137/CMC.S19703) Abstract (http://
15. Bloom MW, Greenberg B, Jaarsma T, et al. Heart failure with reduced ejection fraction. Nat Rev
Dis Primers. 2017 Aug 24;3:17058. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/28836616?
16. Remes J, Reunanen A, Aromaa A, et al. Incidence of heart failure in eastern Finland: a population-
based surveillance study. Eur Heart J. 1992 May;13(5):588-93. Abstract (http://www.ncbi.nlm.nih.gov/
17. Ho KK, Pinsky JL, Kannel WB, et al. The epidemiology of heart failure: the Framingham Study. J Am
Coll Cardiol. 1993 Oct;22(4 Suppl A):6-13A. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/8376698?
18. Senni M, Tribouilloy CM, Rodeheffer RJ, et al. Congestive heart failure in the community: a study of
all incident cases in Olmsted County, Minnesota, in 1991. Circulation. 1998 Nov 24;98(21):2282-9.
19. Chae CU, Pfeffer MA, Glynn RJ, et al. Increased pulse pressure and risk of heart failure in the
elderly. JAMA. 1999 Feb 17;281(7):634-9. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/10029125?
REFERENCES
20. Chen YT, Vaccarino V, Williams CS, et al. Risk factors for heart failure in the elderly: a prospective
community-based study. Am J Med. 1999 Jun;106(6):605-12. Abstract (http://www.ncbi.nlm.nih.gov/
21. Kimmelstiel CD, Konstam MA. Heart failure in women. Cardiology. 1995;86(4):304-9. Abstract (http://
22. Levy D, Larson MG, Vasan RS, et al. The progression from hypertension to congestive heart failure.
JAMA. 1996 May 22-29;275(20):1557-62. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/8622246?
23. Haider AW, Larson MG, Franklin SS, et al. Systolic blood pressure, diastolic blood pressure, and
pulse pressure as predictors of risk for congestive heart failure in the Framingham Heart Study.
Ann Intern Med. 2003 Jan 7;138(1):10-6. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/12513039?
24. Vaccarino V, Holford TR, Krumholz HM. Pulse pressure and risk for myocardial infarction
and heart failure in the elderly. J Am Coll Cardiol. 2000 Jul;36(1):130-8. Full text (http://
www.onlinejacc.org/content/36/1/130) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/10898424?
25. Shindler DM, Kostis JB, Yusuf S, et al. Diabetes mellitus, a predictor of morbidity and mortality in
the Studies of Left Ventricular Dysfunction (SOLVD) trials and registry. Am J Cardiol. 1996 May
1;77(11):1017-20. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/8644628?tool=bestpractice.bmj.com)
26. Kannel WB, Hjortland M, Castelli WP. Role of diabetes in congestive heart failure: the Framingham
study. Am J Cardiol. 1974 Jul;34(1):29-34. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/4835750?
27. Iribarren C, Karter AJ, Go AS, et al. Glycemic control and heart failure among adult patients
with diabetes. Circulation. 2001 Jun 5;103(22):2668-73. Abstract (http://www.ncbi.nlm.nih.gov/
28. Kannel WB, Ho K, Thom T. Changing epidemiological features of cardiac failure. Br Heart J.
1994 Aug;72(2 Suppl):S3-9. Full text (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1025566/
pdf/brheartj00004-0005.pdf) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/7946754?
29. Schillaci G, Vaudo G, Reboldi G, et al. High-density lipoprotein cholesterol and left ventricular
hypertrophy in essential hypertension. J Hypertens. 2001 Dec;19(12):2265-70. Abstract (http://
30. Horio T, Miyazato J, Kamide K, et al. Influence of low high-density lipoprotein cholesterol on
left ventricular hypertrophy and diastolic function in essential hypertension. Am J Hypertens.
83
2003 Nov;16(11 Pt 1):938-44. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/14573332?
REFERENCES
31. Kjekshus J, Pedersen TR, Olsson AG, et al. The effects of simvastatin on the incidence of heart
failure in patients with coronary heart disease. J Card Fail. 1997 Dec;3(4):249-54. Abstract (http://
32. Gottdiener JS, Arnold AM, Aurigemma GP, et al. Predictors of congestive heart failure in the elderly:
the Cardiovascular Health Study. J Am Coll Cardiol. 2000 May;35(6):1628-37. Full text (http://
33. He J, Ogden LG, Bazzano LA, et al. Risk factors for congestive heart failure in US men and women:
NHANES I epidemiologic follow-up study. Arch Intern Med. 2001 Apr 9;161(7):996-1002. Abstract
34. Kenchaiah S, Evans JC, Levy D, et al. Obesity and the risk of heart failure. N Engl J Med. 2002 Aug
1;347(5):305-13. Full text (https://www.nejm.org/doi/10.1056/NEJMoa020245) Abstract (http://
35. Ebong IA, Goff DC Jr, Rodriguez CJ, et al. Mechanisms of heart failure in obesity. Obes Res Clin
Pract. 2014 Nov-Dec;8(6):e540-8. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/25434909?
36. Wilhelmsen L, Rosengren A, Eriksson H, et al. Heart failure in the general population of
men - morbidity, risk factors and prognosis. J Intern Med. 2001 Mar;249(3):253-61. Full text
(https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2796.2001.00801.x) Abstract (http://
37. Facchini FS, Hollenbeck CB, Jeppesen J, et al. Insulin resistance and cigarette smoking. Lancet.
1992 May 9;339(8802):1128-30. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/1349365?
38. Urbano-Marquez A, Estruch R, Navarro-Lopez F, et al. The effects of alcoholism on skeletal and
cardiac muscle. N Engl J Med. 1989 Feb 16;320(7):409-15. Abstract (http://www.ncbi.nlm.nih.gov/
39. Rubin E, Urbano-Marquez A. Alcoholic cardiomyopathy. Alcohol Clin Exp Res. 1994 Feb;18(1):111-4.
40. Walsh CR, Larson MG, Evans JC, et al. Alcohol consumption and risk for congestive heart failure
in the Framingham Heart Study. Ann Intern Med. 2002 Feb 5;136(3):181-91. Abstract (http://
41. Abramson JL, Williams SA, Krumholz HM, et al. Moderate alcohol consumption and risk
of heart failure among older persons. JAMA. 2001 Apr 18;285(15):1971-7. Abstract (http://
42. He J, Ogden LG, Bazzano LA, et al. Dietary sodium intake and incidence of congestive heart failure in
overweight US men and women: first National Health and Nutrition Examination Survey epidemiologic
follow-up study. Arch Intern Med. 2002 Jul 22;162(14):1619-24. Abstract (http://www.ncbi.nlm.nih.gov/
REFERENCES
43. Lee BH, Goodenday LS, Muswick GJ, et al. Alterations in left ventricular diastolic function with
doxorubicin therapy. J Am Coll Cardiol. 1987 Jan;9(1):184-8. Full text (http://www.onlinejacc.org/
content/9/1/184) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/3794095?tool=bestpractice.bmj.com)
44. Nousiainen T, Vanninen E, Jantunen E, et al. Concomitant impairment of left ventricular systolic
and diastolic function during doxorubicin therapy: a prospective radionuclide ventriculographic
and echocardiographic study. Leuk Lymphoma. 2002 Sep;43(9):1807-11. Abstract (http://
45. Swain SM, Whaley FS, Ewer MS. Congestive heart failure in patients treated with doxorubicin:
a retrospective analysis of three trials. Cancer. 2003 Jun 1;97(11):2869-79. Full text (https://
onlinelibrary.wiley.com/doi/full/10.1002/cncr.11407) Abstract (http://www.ncbi.nlm.nih.gov/
46. Gottlieb SL, Edmiston WA J., Haywood LJ. Late, late doxorubicin cardiotoxicity. Chest. 1980
Dec;78(6):880-2. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/7449470?tool=bestpractice.bmj.com)
47. Vasan RS, Larson MG, Benjamin EJ, et al. Left ventricular dilatation and the risk of congestive heart
failure in people without myocardial infarction. N Engl J Med. 1997 May 8;336(19):1350-5. Abstract
48. Kannel WB, Levy D, Cupples LA. Left ventricular hypertrophy and risk of cardiac failure: insights
from the Framingham Study. J Cardiovasc Pharmacol. 1987;10 (Suppl 6):S135-40. Abstract (http://
49. Fried LF, Shlipak MG, Crump C, et al. Renal insufficiency as a predictor of cardiovascular outcomes
and mortality in elderly individuals. J Am Coll Cardiol. 2003 Apr 16;41(8):1364-72. Full text (http://
50. Dries DL, Exner DV, Domanski MJ, et al. The prognostic implications of renal insufficiency in
asymptomatic and symptomatic patients with left ventricular systolic dysfunction. J Am Coll Cardiol.
2000 Mar 1;35(3):681-9. Full text (http://www.onlinejacc.org/content/35/3/681) Abstract (http://
51. Kannel WB, D'Agostino RB, Silbershatz H, et al. Profile for estimating risk of heart failure. Arch Intern
Med. 1999 Jun 14;159(11):1197-204. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/10371227?
52. Carabello BA, Crawford FA Jr. Valvular heart disease. N Engl J Med. 1997 Jul 3;337(1):32-41. Abstract
85
53. Chaudhary BA, Ferguson DS, Speir WA, Jr. Pulmonary edema as a presenting feature of sleep apnea
syndrome. Chest. 1982 Jul;82(1):122-4. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/7083922?
REFERENCES
54. Fletcher EC, Proctor M, Yu J, et al. Pulmonary edema develops after recurrent obstructive apneas.
Am J Respir Crit Care Med. 1999 Nov;160(5 Pt 1):1688-96. Abstract (http://www.ncbi.nlm.nih.gov/
55. Shahar E, Whitney CW, Redline S, et al. Sleep-disordered breathing and cardiovascular
disease: cross-sectional results of the Sleep Heart Health Study. Am J Respir Crit Care
Med. 2001 Jan;163(1):19-25. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/11208620?
56. Abramson J, Berger A, Krumholz HM, et al. Depression and risk of heart failure among older persons
with isolated systolic hypertension. Arch Intern Med. 2001 Jul 23;161(14):1725-30. Abstract (http://
57. Jiang W, Alexander J, Christopher E, et al. Relationship of depression to increased risk of

mortality and rehospitalization in patients with congestive heart failure. Arch Intern Med.
2001 Aug 13-27;161(15):1849-56. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/11493126?
58. Gerstein HC, Mann JF, Yi Q, et al. Albuminuria and risk of cardiovascular events, death, and heart
failure in diabetic and nondiabetic individuals. JAMA. 2001 Jul 25;286(4):421-6. Abstract (http://
59. Vasan RS, Beiser A, D'Agostino RB, et al. Plasma homocysteine and risk for congestive heart failure
in adults without prior myocardial infarction. JAMA. 2003 Mar 12;289(10):1251-7. Abstract (http://
60. Karch SB, Billingham ME. The pathology and etiology of cocaine-induced heart disease. Arch
Pathol Lab Med. 1988 Mar;112(3):225-30. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/3278699?
61. Goldenberg SP, Zeldis SM. Fatal acute congestive heart failure in a patient with idiopathic
hemochromatosis and cocaine use. Chest. 1987 Aug;92(2):374-5. Abstract (http://
62. O'Keefe DD, Grantham RN, Beierholm EA, et al. Cocaine and the contractile response to
catecholamines in right ventricular failure. Am J Physiol. 1977 Sep;233(3):H399-403. Abstract (http://
63. Small KM, Wagoner LE, Levin AM, et al. Synergistic polymorphisms of beta1- and alpha2C-adrenergic
receptors and the risk of congestive heart failure. N Engl J Med. 2002 Oct 10;347(15):1135-42. Full
text (https://www.nejm.org/doi/10.1056/NEJMoa020803) Abstract (http://www.ncbi.nlm.nih.gov/
64. Klip IT, Comin-Colet J, Voors AA, et al. Iron deficiency in chronic heart failure: an international
pooled analysis. Am Heart J. 2013 Apr;165(4):575-82. Full text (https://www.sciencedirect.com/
science/article/pii/S0002870313000744) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/23537975?
REFERENCES
65. Jankowska EA, von Haehling S, Anker SD, et al. Iron deficiency and heart failure: diagnostic
dilemmas and therapeutic perspectives. Eur Heart J. 2013 Mar;34(11):816-29. Full text (https://
academic.oup.com/eurheartj/article/34/11/816/459296) Abstract (http://www.ncbi.nlm.nih.gov/
66. Maeder MT, Khammy O, dos Remedios C, et al. Myocardial and systemic iron depletion in heart failure
implications for anemia accompanying heart failure. J Am Coll Cardiol. 2011 Jul 26;58(5):474-80.
Full text (http://www.onlinejacc.org/content/58/5/474) Abstract (http://www.ncbi.nlm.nih.gov/
67. Meldrum DR. Tumor necrosis factor in the heart. Am J Physiol. 1998 Mar;274(3 Pt 2):R577-95.
68. Vasan RS, Sullivan LM, Roubenoff R, et al. Inflammatory markers and risk of heart failure in
elderly subjects without prior myocardial infarction: the Framingham Heart Study. Circulation.
2003 Mar 25;107(11):1486-91. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/12654604?
69. Welch S, Plank D, Witt S, et al. Cardiac-specific IGF-1 expression attenuates dilated cardiomyopathy
in tropomodulin-overexpressing transgenic mice. Circ Res. 2002 Apr 5;90(6):641-8. Abstract (http://
70. Wang L, Ma W, Markovich R, et al. Regulation of cardiomyocyte apoptotic signaling by insulin-

like growth factor I. Circ Res. 1998 Sep 7;83(5):516-22. Abstract (http://www.ncbi.nlm.nih.gov/
71. Vecchione C, Colella S, Fratta L, et al. Impaired insulin-like growth factor I vasorelaxant effects
in hypertension. Hypertension. 2001 Jun;37(6):1480-5. Abstract (http://www.ncbi.nlm.nih.gov/
72. Vasan RS, Sullivan LM, D'Agostino RB, et al. Serum insulin-like growth factor I and risk for heart
failure in elderly individuals without a previous myocardial infarction: the Framingham Heart Study.
Ann Intern Med. 2003 Oct 21;139(8):642-8. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/14568852?
73. Wang TJ, Larson MG, Levy D, et al. Plasma natriuretic peptide levels and the risk of cardiovascular
events and death. N Engl J Med. 2004 Feb 12;350(7):655-63. Full text (https://www.nejm.org/
74. Wang TJ, Evans JC, Benjamin EJ, et al. Natural history of asymptomatic left ventricular
systolic dysfunction in the community. Circulation. 2003 Aug 26;108(8):977-82. Abstract (http://
75. Aurigemma GP, Gottdiener JS, Shemanski L, et al. Predictive value of systolic and diastolic function
for incident congestive heart failure in the elderly: the cardiovascular health study. J Am Coll Cardiol.
87
2001 Mar 15;37(4):1042-8. Full text (http://www.onlinejacc.org/content/37/4/1042) Abstract (http://
REFERENCES
76. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA guideline on the primary prevention of
cardiovascular disease: a report of the American College of Cardiology/American Heart Association
Task Force on Clinical Practice Guidelines. Circulation. 2019 Sep 10;140(11):e596-e646. Full text
(https://www.doi.org/10.1161/CIR.0000000000000678) Abstract (http://www.ncbi.nlm.nih.gov/
77. Verdecchia P, Angeli F, Cavallini C, et al. Blood pressure reduction and renin-angiotensin
system inhibition for prevention of congestive heart failure: a meta-analysis. Eur Heart J. 2009
Mar;30(6):679-88. Full text (https://academic.oup.com/eurheartj/article/30/6/679/641835) Abstract
78. trandberg TE, Holme I, Faergeman O, et al. Comparative effect of atorvastatin (80 mg)
versus simvastatin (20 to 40 mg) in preventing hospitalizations for heart failure in patients with
previous myocardial infarction. Am J Cardiol. 2009 May 15;103(10):1381-5. Abstract (http://
79. Ho KK, Pinsky JL, Kannel WB, et al. The epidemiology of heart failure: the Framingham Study. J Am
Coll Cardiol. 1993 Oct;22(4 Suppl A):6A-13A. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/8376698?
80. Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA focused update of the 2013
ACCF/AHA guideline for the management of heart failure: a report of the American College
of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and
the Heart Failure Society of America. Circulation. 2017 Aug 8;136(6):e137-61. Full text
(http://circ.ahajournals.org/content/136/6/e137.long) Abstract (http://www.ncbi.nlm.nih.gov/
81. Aimo A, Januzzi JL Jr, Vergaro G, et al. Prognostic value of high-sensitivity troponin T in chronic heart
failure: an individual patient data meta-analysis. Circulation. 2018 Jan 16;137(3):286-97. Full text
(https://www.doi.org/10.1161/CIRCULATIONAHA.117.031560) Abstract (http://www.ncbi.nlm.nih.gov/
82. Asferg C, Usinger L, Kristensen TS, et al. Accuracy of multi-slice computed tomography for
measurement of left ventricular ejection fraction compared with cardiac magnetic resonance imaging
and two-dimensional transthoracic echocardiography: a systematic review and meta-analysis.
Eur J Radiol. 2012 May;81(5):e757-62. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/22381439?
83. Troughton RW, Frampton CM, Yandle TG, et al. Treatment of heart failure guided by
plasma aminoterminal brain natriuretic peptide (N-BNP) concentrations. Lancet. 2000
Apr 1;355(9210):1126-30. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/10791374?
84. Tschope C, Kasner M, Westermann D, et al. The role of NT-proBNP in the diagnostics of isolated
diastolic dysfunction: correlation with echocardiographic and invasive measurements. Eur Heart J.
2005 Nov;26(21):2277-84. Full text (https://academic.oup.com/eurheartj/article/26/21/2277/443408)
REFERENCES
85. Tschope C, Kasner M, Westermann D, et al. Elevated NT-ProBNP levels in patients with increased
left ventricular filling pressure during exercise despite preserved systolic function. J Card Fail.
2005 Jun;11(5 Suppl):S28-33. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/15948097?
86. Maisel A. The coming of age of natriuretic peptides: the emperor does have clothes! J Am Coll
Cardiol. 2006 Jan 3;47(1):61-4. Full text (http://www.onlinejacc.org/content/47/1/61) Abstract (http://
87. Maisel A, Mehra MR. Understanding B-type natriuretic peptide and its role in diagnosing and
monitoring congestive heart failure. Clin Cornerstone. 2005;7 (Suppl 1):S7-17. Abstract (http://
88. Maisel AS, Clopton P, Krishnaswamy P, et al. Impact of age, race, and sex on the ability of B-type
natriuretic peptide to aid in the emergency diagnosis of heart failure: results from the Breathing
Not Properly (BNP) multinational study. Am Heart J. 2004 Jun;147(6):1078-84. Abstract (http://
89. Mueller C, Laule-Kilian K, Schindler C, et al. Cost-effectiveness of B-type natriuretic peptide testing
in patients with acute dyspnea. Arch Intern Med. 2006 May 22;166(10):1081-7. Abstract (http://
90. Mueller C, Laule-Kilian K, Scholer A, et al. Use of B-type natriuretic peptide for the management
of women with dyspnea. Am J Cardiol. 2004 Dec 15;94(12):1510-4. Abstract (http://
91. Mueller C, Scholer A, Laule-Kilian K, et al. Use of B-type natriuretic peptide in the evaluation
and management of acute dyspnea. N Engl J Med. 2004 Feb 12;350(7):647-54. Full text
(https://www.nejm.org/doi/10.1056/NEJMoa031681) Abstract (http://www.ncbi.nlm.nih.gov/
92. Mehra MR, Uber PA, Park MH, et al. Obesity and suppressed B-type natriuretic peptide
levels in heart failure. J Am Coll Cardiol. 2004 May 5;43(9):1590-5. Full text (http://
93. Wang TJ, Larson MG, Keyes MJ, et al. Association of plasma natriuretic peptide levels with metabolic
risk factors in ambulatory individuals. Circulation. 2007 Mar 20;115(11):1345-53. Abstract (http://
94. Wang TJ, Larson MG, Levy D, et al. Impact of obesity on plasma natriuretic peptide levels.
Circulation. 2004 Feb 10;109(5):594-600. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/14769680?
95. Asferg C, Usinger L, Kristensen TS, et al. Accuracy of multi-slice computed tomography for
measurement of left ventricular ejection fraction compared with cardiac magnetic resonance imaging
89
and two-dimensional transthoracic echocardiography: a systematic review and meta-analysis.
Eur J Radiol. 2012 May;81(5):e757-62. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/22381439?
REFERENCES
96. Quinn B, Doyle B, McInerney J. Postnatal pre-cordial pain. Pulmonary embolism or peripartum
cardiomyopathy. Emerg Med J. 2004 Nov;21(6):746-7. Full text (https://www.ncbi.nlm.nih.gov/
pmc/articles/PMC1726479) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/15496714?
97. Chop WM Jr. Extending the New York Heart Association classification system. JAMA. 1985 Jul
26;254(4):505. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/4009875?tool=bestpractice.bmj.com)
98. Nakamura M, Tanaka F, Sato K, et al. B-type natriuretic peptide testing for structural heart disease
screening: a general population-based study. J Card Fail. 2005 Dec;11(9):705-12. Abstract (http://
99. Valle R, Aspromonte N, Barro S, et al. The NT-proBNP assay identifies very elderly nursing
home residents suffering from pre-clinical heart failure. Eur J Heart Fail. 2005 Jun;7(4):542-51.
Full text (https://onlinelibrary.wiley.com/doi/full/10.1016/j.ejheart.2004.07.005) Abstract (http://
100. Aggarwal M, Bozkurt B, Panjrath G, et al. Lifestyle modifications for preventing and
treating heart failure. J Am Coll Cardiol. 2018 Nov 6;72(19):2391-2405. Full text (https://
www.doi.org/10.1016/j.jacc.2018.08.2160) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/30384895?
101. Chatterjee S, Biondi-Zoccai G, Abbate A, et al. Benefits of β blockers in patients with heart
failure and reduced ejection fraction: network meta-analysis. BMJ. 2013 Jan 16;346:f55. Full text
(https://www.doi.org/10.1136/bmj.f55) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/23325883?
102. Kotecha D, Flather MD, Altman DG, et al. Heart rate and rhythm and the benefit of beta-blockers
in patients with heart failure. J Am Coll Cardiol. 2017 Jun 20;69(24):2885-96. Full text (http://
103. Cadrin-Tourigny J, Shohoudi A, Roy D, et al. Decreased mortality with beta-blockers in patients
with heart failure and coexisting atrial fibrillation: an AF-CHF substudy. JACC Heart Fail. 2017
Feb;5(2):99-106. Full text (http://heartfailure.onlinejacc.org/content/5/2/99) Abstract (http://
104. Heran BS, Musini VM, Bassett K, et al. Angiotensin receptor blockers for heart failure. Cochrane
Database Syst Rev. 2012 Apr 18;(4):CD003040. Full text (https://www.cochranelibrary.com/
cdsr/doi/10.1002/14651858.CD003040.pub2/full) Abstract (http://www.ncbi.nlm.nih.gov/
105. Lee VC, Rhew DC, Dylan M, et al. Meta-analysis: angiotensin-receptor blockers in chronic heart failure
and high-risk acute myocardial infarction. Ann Intern Med. 2004 Nov 2;141(9):693-704. [Erratum in:
Ann Intern Med. 2005 Mar 1;42(5):391.] Abstract (http://www.ncbi.nlm.nih.gov/pubmed/15520426?
REFERENCES
106. Wong M, Staszewsky L, Latini R, et al. Severity of left ventricular remodeling defines outcomes and
response to therapy in heart failure: Valsartan heart failure trial (Val-HeFT) echocardiographic data. J
Am Coll Cardiol. 2004 Jun 2;43(11):2022-7. Full text (http://www.onlinejacc.org/content/43/11/2022)
107. Cohn JN, Tognoni G. A randomized trial of the angiotensin-receptor blocker valsartan in chronic
heart failure. N Engl J Med. 2001 Dec 6;345(23):1667-75. Full text (https://www.nejm.org/
108. McMurray JJ, Ostergren J, Swedberg K, et al. Effects of candesartan in patients with chronic heart
failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors:
the CHARM-Added trial. Lancet. 2003 Sep 6;362(9386):767-71. Abstract (http://www.ncbi.nlm.nih.gov/
109. Weir RA, McMurray JJ, Puu M, et al. Efficacy and tolerability of adding an angiotensin receptor blocker
in patients with heart failure already receiving an angiotensin-converting inhibitor plus aldosterone
antagonist, with or without a beta blocker. Findings from the Candesartan in Heart failure: Assessment
of Reduction in Mortality and morbidity (CHARM)-Added trial. Eur J Heart Fail. 2008 Feb;10(2):157-63.
Full text (https://onlinelibrary.wiley.com/doi/full/10.1016/j.ejheart.2007.12.006) Abstract (http://
110. Sakata Y, Shiba N, Takahashi J, et al. Clinical impacts of additive use of olmesartan in hypertensive
patients with chronic heart failure: the supplemental benefit of an angiotensin receptor blocker in
hypertensive patients with stable heart failure using olmesartan (SUPPORT) trial. Eur Heart J. 2015
Apr 14;36(15):915-23. Full text (https://academic.oup.com/eurheartj/article/36/15/915/2293183)
111. European Medicines Agency. PRAC recommends against combined use of medicines affecting the
renin-angiotensin (RAS) system. Apr 2014 [internet publication]. Full text (https://www.ema.europa.eu/
documents/press-release/prac-recommends-against-combined-use-medicines-affecting-renin-
angiotensin-ras-system_en.pdf)
112. McMurray JJ, Krum H, Abraham WT, et al. Aliskiren, enalapril, or aliskiren and enalapril in
heart failure. N Engl J Med. 2016 Apr 21;374(16):1521-32. Full text (https://www.nejm.org/
113. McMurray JJ, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in
heart failure. N Engl J Med. 2014 Sep 11;371(11):993-1004. Full text (https://www.nejm.org/
114. Chandra A, Lewis EF, Claggett BL, et al. Effects of sacubitril/valsartan on physical and social
activity limitations in patients with heart failure: a secondary analysis of the PARADIGM-HF trial.
91
JAMA Cardiol. 2018 Jun 1;3(6):498-505. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/29617523?
REFERENCES
115. Desai AS, McMurray JJ, Packer M, et al. Effect of the angiotensin-receptor-neprilysin inhibitor
LCZ696 compared with enalapril on mode of death in heart failure patients. Eur Heart J. 2015 Aug
7;36(30):1990-7. Full text (https://academic.oup.com/eurheartj/article/36/30/1990/2398127) Abstract
116. Carson P, Ziesche S, Johnson G, et al; Vasodilator-Heart Failure Trial Study Group. Racial differences
in response to therapy for heart failure: analysis of the vasodilator-heart failure trials. J Card Fail. 1999
Sep;5(3):178-87. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/10496190?tool=bestpractice.bmj.com)
117. Taylor AL, Ziesche S, Yancy C, et al. Combination of isosorbide dinitrate and hydralazine in blacks
with heart failure. N Engl J Med. 2004 Nov 11;351(20):2049-57. Full text (https://www.nejm.org/
118. Shantsila E, Kozieł M, Lip GY. Anticoagulation versus placebo for heart failure in sinus rhythm.
Cochrane Database Syst Rev. 2021 May 18;5:CD003336. Full text (https://www.cochranelibrary.com/
cdsr/doi/10.1002/14651858.CD003336.pub4/full) Abstract (http://www.ncbi.nlm.nih.gov/
119. Homma S, Thompson JL, Pullicino PM, et al. Warfarin and aspirin in patients with heart failure
and sinus rhythm. N Engl J Med. 2012 May 17;366(20):1859-69. Full text (https://www.nejm.org/
120. oy D, Talajic M, Nattel S, et al. Rhythm control versus rate control for atrial fibrillation and
heart failure. N Engl J Med. 2008 Jun 19;358(25):2667-77. Full text (https://www.nejm.org/
121. Gheorghiade M, Patel K, Filippatos G, et al. Effect of oral digoxin in high-risk heart failure patients:
a pre-specified subgroup analysis of the DIG trial. Eur J Heart Fail. 2013 May;15(5):551-9. Full text
(https://onlinelibrary.wiley.com/doi/full/10.1093/eurjhf/hft010) Abstract (http://www.ncbi.nlm.nih.gov/
122. Vamos M, Erath JW, Hohnloser SH, et al. Digoxin-associated mortality: a systematic review and meta-
analysis of the literature. Eur Heart J. 2015 Jul 21;36(28):1831-8. Full text (https://academic.oup.com/
eurheartj/article/36/28/1831/2398087) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/25939649?
123. Ziff OJ, Lane DA, Samra M, et al. Safety and efficacy of digoxin: systematic review and meta-
analysis of observational and controlled trial data. BMJ. 2015 Aug 30;351:h4451. Full text
(https://www.bmj.com/content/351/bmj.h4451.long) Abstract (http://www.ncbi.nlm.nih.gov/
124. Fox K, Ford I, Steg PG, et al. Ivabradine in stable coronary artery disease without clinical
heart failure. N Engl J Med. 2014 Sep 18;371(12):1091-9. Full text (https://www.nejm.org/doi/
full/10.1056/NEJMoa1406430) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/25176136?
REFERENCES
125. Pitt B, Bakris G, Ruilope LM, et al. Serum potassium and clinical outcomes in the Eplerenone Post-
Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS). Circulation.
2008 Oct 14;118(16):1643-50. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/18824643?
126. National Institute for Health and Care Excellence. Ivabradine for treating chronic heart failure. Nov
2012 [internet publication]. Full text (https://www.nice.org.uk/guidance/ta267)
127. Ezekowitz JA, O'Meara E, McDonald MA, et al. 2017 comprehensive update of the Canadian
Cardiovascular Society guidelines for themanagement of heart failure. Can J Cardiol. 2017
Nov;33(11):1342-1433. Full text (https://www.doi.org/10.1016/j.cjca.2017.08.022) Abstract (http://
128. Mudge GH, Goldstein S, Addonizio LJ, et al. 24th Bethesda conference: Cardiac transplantation.
Task Force 3: Recipient guidelines/prioritization. J Am Coll Cardiol. 1993 Jul;22(1):21-31. Full text
(http://www.onlinejacc.org/content/22/1/21) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/8509544?
129. Mehra MR, Canter CE, Hannan MM, et al. The 2016 International Society for Heart Lung
Transplantation listing criteria for heart transplantation: a 10-year update. J Heart Lung
Transplant. 2016 Jan;35(1):1-23. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/26776864?
130. Mehra MR, Kobashigawa JA. Advances in heart and lung transplantation 2004: report from the 24th
International Society for Heart and Lung Transplantation Annual Meeting, San Francisco, 21-24
April 2004. J Heart Lung Transplant. 2004 Aug;23(8):925-30. Abstract (http://www.ncbi.nlm.nih.gov/
131. Miller LW. Listing criteria for cardiac transplantation: results of an American Society of Transplant
Physicians-National Institutes of Health conference. Transplantation. 1998 Oct 15;66(7):947-51.
132. Bardy GH, Lee KL, Mark DB, Poole JE, et al; Sudden Cardiac Death in Heart Failure Trial (SCD-
HeFT) Investigators. Amiodarone or an implantable cardioverter-defibrillator for congestive
heart failure. N Engl J Med. 2005 Jan 20;352(3):225-37. Full text (https://www.nejm.org/doi/
full/10.1056/NEJMoa043399) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/15659722?
133. Jarcho JA. Biventricular pacing. N Engl J Med. 2006 Jul 20;355(3):288-94. Abstract (http://
134. Bristow MR, Saxon LA, Boehmer J, et al. Cardiac-resynchronization therapy with or without
an implantable defibrillator in advanced chronic heart failure. N Engl J Med. 2004 May
20;350(21):2140-50. Full text (https://www.nejm.org/doi/10.1056/NEJMoa032423) Abstract (http://
93
135. De Marco T, Wolfel E, Feldman AM, et al. Impact of cardiac resynchronization therapy on exercise
performance, functional capacity, and quality of life in systolic heart failure with QRS prolongation:
COMPANION trial sub-study. J Card Fail. 2008 Feb;14(1):9-18. Abstract (http://www.ncbi.nlm.nih.gov/
REFERENCES
136. Linde C, Abraham WT, Gold MR, et al. Randomized trial of cardiac resynchronization in mildly
symptomatic heart failure patients and in asymptomatic patients with left ventricular dysfunction and
previous heart failure symptoms. J Am Coll Cardiol. 2008 Dec 2;52(23):1834-43. Full text (http://
137. Mark DB, Anstrom KJ, Sun JL, et al. Quality of life with defibrillator therapy or amiodarone in
heart failure. N Engl J Med. 2008 Sep 4;359(10):999-1008. Full text (https://www.nejm.org/
138. Bertoldi EG, Polanczyk CA, Cunha V, et al. Mortality reduction of cardiac resynchronization and
implantable cardioverter-defibrillator therapy in heart failure: an updated meta-analysis. Does
recent evidence change the standard of care? J Card Fail. 2011 Oct;17(10):860-6. Abstract (http://
139. Cleland JG, Freemantle N, Erdmann E, et al. Long-term mortality with cardiac resynchronization
therapy in the Cardiac Resynchronization-Heart Failure (CARE-HF) trial. Eur J Heart Fail. 2012
Jun;14(6):628-34. Full text (https://onlinelibrary.wiley.com/doi/full/10.1093/eurjhf/hfs055) Abstract
140. Cazeau S, Leclercq C, Lavergne T, et al. Effects of multisite biventricular pacing in patients with heart
failure and intraventricular conduction delay. N Engl J Med. 2001 Mar 22;344(12):873-80. Full text
(https://www.nejm.org/doi/10.1056/NEJM200103223441202) Abstract (http://www.ncbi.nlm.nih.gov/
141. Nelson GS, Berger RD, Fetics BJ, et al. Left ventricular or biventricular pacing improves cardiac
function at diminished energy cost in patients with dilated cardiomyopathy and left bundle-
branch block. Circulation. 2000 Dec 19;102(25):3053-9. Abstract (http://www.ncbi.nlm.nih.gov/
142. Abraham WT, Fisher WG, Smith AL, et al. Cardiac resynchronization in chronic heart failure. N Engl
J Med. 2002 Jun 13;346(24):1845-53. Full text (https://www.nejm.org/doi/10.1056/NEJMoa013168)
143. Cleland JG, Daubert JC, Erdmann E, et al. The CARE-HF study (CArdiac REsynchronisation in Heart
Failure study): rationale, design and end-points. Eur J Heart Fail. 2001 Aug;3(4):481-9. Full text
(https://onlinelibrary.wiley.com/doi/full/10.1016/S1388-9842%2801%2900176-3) Abstract (http://
144. Cleland JG, Daubert JC, Erdmann E, et al. Longer-term effects of cardiac resynchronization
therapy on mortality in heart failure [the CArdiac REsynchronization-Heart Failure (CARE-HF) trial
extension phase]. Eur Heart J. 2006 Aug;27(16):1928-32. Full text (https://academic.oup.com/
REFERENCES
145. Calvert MJ, Freemantle N, Cleland JG. The impact of chronic heart failure on health-related quality
of life data acquired in the baseline phase of the CARE-HF study. Eur J Heart Fail. 2005 Mar
2;7(2):243-51. Full text (https://onlinelibrary.wiley.com/doi/full/10.1016/j.ejheart.2005.01.012)
146. Calvert MJ, Freemantle N, Yao G, et al. Cost-effectiveness of cardiac resynchronization

therapy: results from the CARE-HF trial. Eur Heart J. 2005 Dec;26(24):2681-8. Full text (https://
academic.oup.com/eurheartj/article/26/24/2681/2888051) Abstract (http://www.ncbi.nlm.nih.gov/
147. Ellenbogen KA, Wood MA, Klein HU. Why should we care about CARE-HF? J Am Coll Cardiol. 2005
Dec 20;46(12):2199-203. Full text (http://www.onlinejacc.org/content/46/12/2199) Abstract (http://
148. Hoppe UC, Casares JM, Eiskjaer H, et al. Effect of cardiac resynchronization on the incidence of atrial
fibrillation in patients with severe heart failure. Circulation. 2006 Jul 4;114(1):18-25. Abstract (http://
149. Cleland JG, Daubert JC, Erdmann E, et al. Baseline characteristics of patients recruited into the
CARE-HF study. Eur J Heart Fail. 2005 Mar 2;7(2):205-14. Full text (https://onlinelibrary.wiley.com/
doi/abs/10.1016/j.ejheart.2005.01.010) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/15701468?
150. Cleland JG, Daubert JC, Erdmann E, et al. The effect of cardiac resynchronization on morbidity and
mortality in heart failure. N Engl J Med. 2005 Apr 14;352(15):1539-49. Full text (https://www.nejm.org/
151. leland JG, Calvert MJ, Verboven Y, et al. Effects of cardiac resynchronization therapy on long-term
quality of life: an analysis from the CArdiac Resynchronisation-Heart Failure (CARE-HF) study.
Am Heart J. 2009 Mar;157(3):457-66. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/19249415?
152. Ghio S, Freemantle N, Scelsi L, et al. Long-term left ventricular reverse remodelling with
cardiac resynchronization therapy: results from the CARE-HF trial. Eur J Heart Fail. 2009
May;11(5):480-8. Full text (https://onlinelibrary.wiley.com/doi/full/10.1093/eurjhf/hfp034) Abstract
153. Cleland J, Freemantle N, Ghio S, et al. Predicting the long-term effects of cardiac resynchronization
therapy on mortality from baseline variables and the early response a report from the CARE-HF
(Cardiac Resynchronization in Heart Failure) Trial. J Am Coll Cardiol. 2008 Aug 5;52(6):438-45.
154. Lindenfeld J, Feldman AM, Saxon L, et al. Effects of cardiac resynchronization therapy with or without
a defibrillator on survival and hospitalizations in patients with New York Heart Association class
95
IV heart failure. Circulation. 2007 Jan 16;115(2):204-12. Abstract (http://www.ncbi.nlm.nih.gov/
REFERENCES
155. Daubert C, Gold MR, Abraham WT, et al. Prevention of disease progression by cardiac
resynchronization therapy in patients with asymptomatic or mildly symptomatic left
ventricular dysfunction. J Am Coll Cardiol. 2009 Nov 10;54(20):1837-46. Full text (http://
156. Linde C, Gold MR, Abraham WT, et al. REVERSE study: CRT produces long-term improvements
in disease progression in mildly symptomatic heart failure patients. Five-year results from the
REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction study. Paper
presented at: European Society of Cardiology Congress 2012. 27 August 2012. Munich, Germany.
157. Peura JL, Colvin-Adams M, Francis GS, et al. Recommendations for the use of mechanical circulatory
support: device strategies and patient selection. A scientific statement from the American Heart
Association. Circulation. 2012 Nov 27;126(22):2648-67. Full text (https://www.ahajournals.org/doi/
full/10.1161/cir.0b013e3182769a54) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/23109468?
158. Gopinathannair R, Cornwell WK, Dukes JW, et al. Device therapy and arrhythmia management
in left ventricular assist device recipients: a scientific statement from the American Heart
Association. Circulation. 2019 May 14;139(20):e967-e989. Full text (https://www.doi.org/10.1161/
CIR.0000000000000673) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/30943783?
159. Cook JL, Colvin M, Francis GS, et al. Recommendations for the use of mechanical circulatory support:
ambulatory and community patient care: a scientific statement from the American Heart Association.
Circulation. 2017 Jun 20;135(25):e1145-58. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/28559233?
160. Zwisler AD, Soja AM, Rasmussen S, et al. Hospital-based comprehensive cardiac rehabilitation
versus usual care among patients with congestive heart failure, ischemic heart disease, or
high risk of ischemic heart disease: 12-month results of a randomized clinical trial. Am Heart
J. 2008 Jun;155(6):1106-13. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/18513526?
161. Poole-Wilson PA, Swedberg K, Cleland JG, et al. Comparison of carvedilol and metoprolol on
clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European
Trial (COMET): randomised controlled trial. Lancet. 2003 Jul 5;362(9377):7-13. Abstract (http://
162. Flather MD, Shibata MC, Coats AJ, et al. Randomized trial to determine the effect of nebivolol
on mortality and cardiovascular hospital admission in elderly patients with heart failure
(SENIORS). Eur Heart J. 2005 Feb;26(3):215-25. Full text (https://academic.oup.com/
163. Triposkiadis F, Giamouzis G, Kelepeshis G, et al. Acute hemodynamic effects of moderate doses
of nebivolol versus metoprolol in patients with systolic heart failure. Int J Clin Pharmacol Ther. 2007
Feb;45(2):71-7. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/17323786?tool=bestpractice.bmj.com)
REFERENCES
164. Richardson A, Bayliss J, Scriven AJ, et al. Double-blind comparison of captopril alone against
frusemide plus amiloride in mild heart failure. Lancet. 1987 Sep 26;2(8561):709-11. Abstract (http://
165. Captopril-Digoxin Multicenter Research Group. Comparative effects of therapy with captopril and
digoxin in patients with mild to moderate heart failure. JAMA. 1988 Jan 22-29;259(4):539-44. Abstract
166. Wilson JR, Reichek N, Dunkman WB, et al. Effect of diuresis on the performance of the failing
left ventricle in man. Am J Med. 1981 Feb;70(2):234-9. Abstract (http://www.ncbi.nlm.nih.gov/
167. Elkayam U, Johnson JV, Shotan A, et al. Double-blind, placebo-controlled study to evaluate the
effect of organic nitrates in patients with chronic heart failure treated with angiotensin-converting
enzyme inhibition. Circulation. 1999 May 25;99(20):2652-7. Abstract (http://www.ncbi.nlm.nih.gov/
168. Elkayam U, Karaalp IS, Wani OR, et al. The role of organic nitrates in the treatment of heart
failure. Prog Cardiovasc Dis. 1999 Jan-Feb;41(4):255-64. Abstract (http://www.ncbi.nlm.nih.gov/
169. Watanabe H, Kakihana M, Ohtsuka S, et al. Preventive effects of carvedilol on nitrate tolerance - a
randomized, double-blind, placebo-controlled comparative study between carvedilol and arotinolol.
J Am Coll Cardiol. 1998 Nov;32(5):1201-6. Full text (http://www.onlinejacc.org/content/32/5/1201)
170. Watanabe H, Kakihana M, Ohtsuka S, et al. Randomized, double-blind, placebo-controlled study of

carvedilol on the prevention of nitrate tolerance in patients with chronic heart failure. J Am Coll Cardiol.
1998 Nov;32(5):1194-200. Full text (http://www.onlinejacc.org/content/32/5/1194) Abstract (http://
171. Bauer JA, Fung HL. Concurrent hydralazine administration prevents nitroglycerin-induced
hemodynamic tolerance in experimental heart failure. Circulation. 1991 Jul;84(1):35-9. Abstract (http://
172. Gogia H, Mehra A, Parikh S, et al. Prevention of tolerance to hemodynamic effects of nitrates
with concomitant use of hydralazine in patients with chronic heart failure. J Am Coll Cardiol. 1995
Dec;26(7):1575-80. Full text (http://www.onlinejacc.org/content/26/7/1575) Abstract (http://
173. Fogelman AM, La Mont JT, Finkelstein S, et al. Fallibility of plasma-digoxin in differentiating toxic
from non-toxic patients. Lancet. 1971 Oct 2;2(7727):727-9. Abstract (http://www.ncbi.nlm.nih.gov/
97
174. Ingelfinger JA, Goldman P. The serum digitalis concentration - does it diagnose digitalis toxicity? N
Engl J Med. 1976 Apr 15;294(16):867-70. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/1250314?
REFERENCES
175. Jelliffe RW, Brooker G. A nomogram for digoxin therapy. Am J Med. 1974 Jul;57(1):63-8. Abstract
176. Massie B, Chatterjee K, Werner J, et al. Hemodynamic advantage of combined administration of

hydralazine orally and nitrates nonparenterally in the vasodilator therapy of chronic heart failure.
Am J Cardiol. 1977 Nov;40(5):794-801. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/411364?
177. Pierpont GL, Cohn JN, Franciosa JA. Combined oral hydralazine-nitrate therapy in left ventricular
failure. Hemodynamic equivalency to sodium nitroprusside. Chest. 1978 Jan;73(1):8-13. Abstract
178. Landoni G, Biondi-Zoccai G, Greco M, et al. Effects of levosimendan on mortality and hospitalization.
A meta-analysis of randomized controlled studies. Crit Care Med. 2012 Feb;40(2):634-46. Abstract
179. Follath F, Cleland JG, Just H, et al. Efficacy and safety of intravenous levosimendan compared with
dobutamine in severe low-output heart failure (the LIDO study): a randomised double-blind trial.
Lancet. 2002 Jul 20;360(9328):196-202. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/12133653?
180. Adamopoulos S, Parissis JT, Iliodromitis EK, et al. Effects of levosimendan versus dobutamine
on inflammatory and apoptotic pathways in acutely decompensated chronic heart failure. Am
J Cardiol. 2006 Jul 1;98(1):102-6. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/16784930?
181. Tavazzi L, Maggioni AP, Marchioli R, et al; Gissi-HF Investigators. Effect of n-3 polyunsaturated
fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind,
placebo-controlled trial. Lancet. 2008 Oct 4;372(9645):1223-30. Abstract (http://www.ncbi.nlm.nih.gov/
182. Kwak SM, Myung SK, Lee YJ, et al. Efficacy of omega-3 fatty acid supplements (eicosapentaenoic
acid and docosahexaenoic acid) in the secondary prevention of cardiovascular disease:
a meta-analysis of randomized, double-blind, placebo-controlled trials. Arch Intern Med.
2012 May 14;172(9):686-94. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/22493407?
183. Torre-Amione G, Anker SD, Bourge RC, et al. Results of a non-specific immunomodulation
therapy in chronic heart failure (ACCLAIM trial): a placebo-controlled randomised trial. Lancet.
2008 Jan 19;371(9608):228-36. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/18207018?
184. ritos NA, Danias PG. Growth hormone therapy in congestive heart failure due to left ventricular
systolic dysfunction: a meta-analysis. Endocr Pract. 2008 Jan-Feb;14(1):40-9. Abstract (http://
REFERENCES
185. Le Corvoisier P, Hittinger L, Chanson P, et al. Cardiac effects of growth hormone treatment in chronic
heart failure: a meta-analysis. J Clin Endocrinol Metab. 2007 Jan;92(1):180-5. Abstract (http://
186. Zhang L, Lu Y, Jiang H, et al. Additional use of trimetazidine in patients with chronic heart
failure: a meta-analysis. J Am Coll Cardiol. 2012 Mar 6;59(10):913-22. Full text (http://
187. McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in patients with heart failure and
reduced ejection fraction. N Engl J Med. 2019 Nov 21;381(21):1995-2008. Full text (https://
www.doi.org/10.1056/NEJMoa1911303) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/31535829?
188. Abi-Samra F, Gutterman D. Cardiac contractility modulation: a novel approach for the
treatment of heart failure. Heart Fail Rev. 2016 Nov;21(6):645-60. Full text (https://
www.doi.org/10.1007/s10741-016-9571-6) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/27394714?
189. Abraham WT, Zile MR, Weaver FA, et al. Baroreflex activation therapy for the treatment of heart
failure with a reduced ejection fraction. JACC Heart Fail. 2015 Jun;3(6):487-96. Full text (https://
www.doi.org/10.1016/j.jchf.2015.02.006) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/25982108?
190. Sánchez LA, Guerrero-Beltrán CE, Cordero-Reyes AM, et al. Use of stem cells in heart failure
treatment: where we stand and where we are going. Methodist Debakey Cardiovasc J. 2013 Oct-
Dec;9(4):195-200. Full text (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3846072) Abstract (http://
191. Fisher SA, Doree C, Mathur A, et al. Stem cell therapy for chronic ischaemic heart disease and
congestive heart failure. Cochrane Database Syst Rev. 2016 Dec 24;(12):CD007888. Full text
(https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007888.pub3/full) Abstract (http://
192. Tilemann L, Ishikawa K, Weber T, et al. Gene therapy for heart failure. Circ Res. 2012 Mar
2;110(5):777-93. Full text (https://www.ahajournals.org/doi/full/10.1161/CIRCRESAHA.111.252981)
193. Hammond HK, Penny WF, Traverse JH, et al. Intracoronary gene transfer of adenylyl cyclase 6
in patients with heart failure: a randomized clinical trial. JAMA Cardiol. 2016 May 1;1(2):163-71.
Full text (https://jamanetwork.com/journals/jamacardiology/fullarticle/2506673) Abstract (http://
194. Greenberg B, Butler J, Felker GM, et al. Calcium upregulation by percutaneous administration of
gene therapy in patients with cardiac disease (CUPID 2): a randomised, multinational, double-
99
blind, placebo-controlled, phase 2b trial. Lancet. 2016 Mar 19;387(10024):1178-86. Abstract (http://
REFERENCES
195. Klein P, Bax JJ, Shaw LJ, et al. Early and late outcome of left ventricular reconstruction surgery
in ischemic heart disease. Eur J Cardiothorac Surg. 2008 Dec;34(6):1149-57. Full text (https://
academic.oup.com/ejcts/article/34/6/1149/337090) Abstract (http://www.ncbi.nlm.nih.gov/
196. Bolling SF, Pagani FD, Deeb GM, et al. Intermediate-term outcome of mitral reconstruction in
cardiomyopathy. J Thorac Cardiovasc Surg. 1998 Feb;115(2):381-8. Full text (https://www.jtcvs.org/
article/S0022-5223(98)70282-X/fulltext) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/9475533?
197. Wu AH, Aaronson KD, Bolling SF, et al. Impact of mitral valve annuloplasty on mortality risk
in patients with mitral regurgitation and left ventricular systolic dysfunction. J Am Coll Cardiol.
2005 Feb 1;45(3):381-7. Full text (http://www.onlinejacc.org/content/45/3/381) Abstract (http://
198. Athanasuleas CL, Stanley AW, Jr., Buckberg GD, et al. Surgical anterior ventricular endocardial
restoration (SAVER) in the dilated remodeled ventricle after anterior myocardial infarction:
RESTORE group – Reconstructive Endoventricular Surgery, returning Torsion Original Radius
Elliptical Shape to the LV. J Am Coll Cardiol. 2001 Apr;37(5):1199-209. Full text (http://
199. Anker SD, Kirwan BA, van Veldhuisen DJ, et al. Effects of ferric carboxymaltose on hospitalisations
and mortality rates in iron-deficient heart failure patients: an individual patient data meta-analysis. Eur
J Heart Fail. 2018 Jan;20(1):125-33. Full text (https://www.doi.org/10.1002/ejhf.823) Abstract (http://
200. Lund LH, Aaronson KD, Mancini DM. Predicting survival in ambulatory patients with severe
heart failure on beta-blocker therapy. Am J Cardiol. 2003 Dec 1;92(11):1350-4. Abstract (http://
201. Aaronson KD, Schwartz JS, Chen TM, et al. Development and prospective validation of a
clinical index to predict survival in ambulatory patients referred for cardiac transplant evaluation.
Circulation. 1997 Jun 17;95(12):2660-7. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/9193435?
202. Levy WC, Mozaffarian D, Linker DT, et al. The Seattle Heart Failure Model: prediction of survival in
heart failure. Circulation. 2006 Mar 21;113(11):1424-33. Full text (https://www.ahajournals.org/doi/
full/10.1161/circulationaha.105.584102) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/16534009?
203. Lee DS, Austin PC, Rouleau JL, et al. Predicting mortality among patients hospitalized for heart
failure: derivation and validation of a clinical model. JAMA. 2003 Nov 19;290(19):2581-7. Abstract
204. Fonarow GC, Adams KF, Jr., Abraham WT, et al. Risk stratification for in-hospital mortality in
acutely decompensated heart failure: classification and regression tree analysis. JAMA. 2005 Feb
2;293(5):572-80. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/15687312?tool=bestpractice.bmj.com)
REFERENCES
205. Brophy JM, Dagenais GR, McSherry F, et al. A multivariate model for predicting mortality in patients
with heart failure and systolic dysfunction. Am J Med. 2004 Mar 1;116(5):300-4. Abstract (http://
206. Koelling TM, Joseph S, Aaronson KD. Heart failure survival score continues to predict clinical
outcomes in patients with heart failure receiving beta-blockers. J Heart Lung Transplant.
2004 Dec;23(12):1414-22. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/15607672?
207. Raphael CE, Whinnett ZI, Davies JE, et al. Quantifying the paradoxical effect of higher systolic
blood pressure on mortality in chronic heart failure. Heart. 2009 Jan;95(1):56-62. Abstract (http://
208. Gerstein HC, Swedberg K, Carlsson J, et al. The hemoglobin A1c level as a progressive risk factor
for cardiovascular death, hospitalization for heart failure, or death in patients with chronic heart
failure: an analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and
Morbidity (CHARM) program. Arch Intern Med. 2008 Aug 11;168(15):1699-704. Abstract (http://
209. Castel MA, Magnani S, Mont L, et al. Survival in New York Heart Association class IV heart
failure patients treated with cardiac resynchronization therapy compared with patients on optimal
pharmacological treatment. Europace. 2010 Aug;12(8):1136-40. Full text (https://academic.oup.com/
europace/article/12/8/1136/449076) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/20543199?
210. Ammar KA, Jacobsen SJ, Mahoney DW, et al. Prevalence and prognostic significance of heart
failure stages: application of the American College of Cardiology/American Heart Association heart
failure staging criteria in the community. Circulation. 2007 Mar 27;115(12):1563-70. Abstract (http://
211. Rangaswami J, Bhalla V, Blair JEA, et al. Cardiorenal syndrome: classification, pathophysiology,
diagnosis, and treatment strategies: a scientific statement from the American Heart
Association. Circulation. 2019 Apr 16;139(16):e840-78. Full text (https://www.doi.org/10.1161/
CIR.0000000000000664) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/30852913?
212. Philbin EF, Santella RN, Rocco TA Jr. Angiotensin-converting enzyme inhibitor use in older patients
with heart failure and renal dysfunction. J Am Geriatr Soc. 1999 Mar;47(3):302-8. Abstract (http://
213. Arnold SB, Byrd RC, Meister W, et al. Long-term digitalis therapy improves left ventricular function
in heart failure. N Engl J Med. 1980 Dec 18;303(25):1443-8. Abstract (http://www.ncbi.nlm.nih.gov/
101
214. Turini GA, Waeber B, Brunner HR. The renin-angiotensin system in refractory heart failure: clinical,
hemodynamic and hormonal effects of captopril and enalapril. Eur Heart J. 1983 Jan;4 (Suppl
A):189-97. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/6301835?tool=bestpractice.bmj.com)
REFERENCES
215. Weinfeld MS, Chertow GM, Stevenson LW. Aggravated renal dysfunction during intensive therapy
for advanced chronic heart failure. Am Heart J. 1999 Aug;138(2 Pt 1):285-90. Abstract (http://
216. Alpert MA. Cardiovascular factors influencing survival in dialysis patients. Adv Perit Dial.
1996;12:110-9. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/8865884?tool=bestpractice.bmj.com)
217. Besarab A, Bolton WK, Browne JK, et al. The effects of normal as compared with low hematocrit
values in patients with cardiac disease who are receiving hemodialysis and epoetin. N Engl J Med.
1998 Aug 27;339(9):584-90. Full text (https://www.nejm.org/doi/10.1056/NEJM199808273390903)
218. Risler T, Schwab A, Kramer B, et al. Comparative pharmacokinetics and pharmacodynamics of loop
diuretics in renal failure. Cardiology. 1994;84 (Suppl 2):155-61. Abstract (http://www.ncbi.nlm.nih.gov/
219. Iorio L. Daily hemofiltration in severe heart failure. Int J Artif Organs. 1998 Dec;21(12):778-80.
220. Iorio L, Nacca RG, Simonelli R, et al. Daily hemofiltration in severe heart failure. Miner Electrolyte
Metab. 1999 Jan-Apr;25(1-2):39-42. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/10207257?
221. Iorio L, Simonelli R, Nacca RG, et al. Daily hemofiltration in severe heart failure. Kidney
Int Suppl. 1997 Jun;59:S62-5. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/9185107?
222. Iorio L, Simonelli R, Nacca RG, et al. The benefits of daily hemofiltration in the management of anuria
in patients with severe heart failure (NYHA IV). Int J Artif Organs. 1998 Aug;21(8):457-9. Abstract
223. Horwich TB, Fonarow GC, Hamilton MA, et al. Anemia is associated with worse symptoms,
greater impairment in functional capacity and a significant increase in mortality in patients
with advanced heart failure. J Am Coll Cardiol. 2002 Jun 5;39(11):1780-6. Full text (http://
224. Al-Ahmad A, Rand WM, Manjunath G, et al. Reduced kidney function and anemia as risk factors
for mortality in patients with left ventricular dysfunction. J Am Coll Cardiol. 2001 Oct;38(4):955-62.
225. Silverberg DS, Wexler D, Blum M, et al. The use of subcutaneous erythropoietin and intravenous
iron for the treatment of the anemia of severe, resistant congestive heart failure improves cardiac
and renal function and functional cardiac class, and markedly reduces hospitalizations. J Am
Coll Cardiol. 2000 Jun;35(7):1737-44. Abstract (http://www.ncbi.nlm.nih.gov/pubmed/10841219?
REFERENCES
226. Silverberg DS, Wexler D, Sheps D, et al. The effect of correction of mild anemia in severe,
resistant congestive heart failure using subcutaneous erythropoietin and intravenous iron: a
randomized controlled study. J Am Coll Cardiol. 2001 Jun 1;37(7):1775-80. Full text (http://
227. Mancini DM, Katz SD, Lang CC, et al. Effect of erythropoietin on exercise capacity in patients with
moderate to severe chronic heart failure. Circulation. 2003 Jan 21;107(2):294-9. Abstract (http://
228. hali JK, Anand IS, Abraham WT, et al. Randomized double-blind trial of darbepoetin alfa in patients
with symptomatic heart failure and anemia. Circulation. 2008 Jan 29;117(4):526-35. Abstract (http://
229. 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. J Am Coll Cardiol. 2013 Oct 15;62(16):e147-239. Full text (http://
www.onlinejacc.org/content/62/16/e147) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/23747642?
230. Troughton RW, Frampton CM, Brunner-La Rocca HP, et al. Effect of B-type natriuretic peptide-
guided treatment of chronic heart failure on total mortality and hospitalization: an individual patient
meta-analysis. Eur Heart J. 2014 Jun 14;35(23):1559-67. Full text (https://academic.oup.com/
231. Felker GM, Anstrom KJ, Adams KF, et al. Effect of natriuretic peptide-guided therapy on hospitalization
or cardiovascular mortality in high-risk patients with heart failure and reduced ejection fraction: a
randomized clinical trial. JAMA. 2017 Aug 22;318(8):713-20. Full text (https://jamanetwork.com/
journals/jama/fullarticle/2649188) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/28829876?
232. Chaudhry SI, Phillips CO, Stewart SS, et al. Telemonitoring for patients with chronic heart failure:
a systematic review. J Card Fail. 2007 Feb;13(1):56-62. Abstract (http://www.ncbi.nlm.nih.gov/
233. Clark RA, Inglis SC, McAlister FA, et al. Telemonitoring or structured telephone support programmes
for patients with chronic heart failure: systematic review and meta-analysis. BMJ. 2007 May
5;334(7600):942. Full text (https://www.bmj.com/content/334/7600/942.long) Abstract (http://
234. Abraham WT, Adamson PB, Bourge RC, et al. Wireless pulmonary artery haemodynamic monitoring
in chronic heart failure: a randomised controlled trial. Lancet. 2011 Feb 19;377(9766):658-66. Abstract
103
235. Inglis SC, Clark RA, Dierckx R, et al. Structured telephone support or non-invasive telemonitoring
for patients with heart failure. Cochrane Database Syst Rev. 2015 Oct 31;(10):CD007228. Full text
(https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD007228.pub3/full) Abstract (http://
REFERENCES
236. Ades PA, Keteyian SJ, Balady GJ, et al. Cardiac rehabilitation exercise and self-
care for chronic heart failure. JACC Heart Fail. 2013 Dec;1(6):540-7. Full text (http://
heartfailure.onlinejacc.org/content/1/6/540) Abstract (http://www.ncbi.nlm.nih.gov/pubmed/24622007?
237. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC guidelines for the diagnosis and treatment
238. Piepoli MF, Conraads V, Corrà U, et al. Exercise training in heart failure: from theory to practice.
A consensus document of the Heart Failure Association and the European Association for
Cardiovascular Prevention and Rehabilitation. Eur J Heart Fail. 2011 Apr;13(4):347-57. Full text
(https://onlinelibrary.wiley.com/doi/full/10.1093/eurjhf/hfr017) Abstract (http://www.ncbi.nlm.nih.gov/
Chronic congestive heart failure Disclaimer
Disclaimer
BMJ Best Practice is intended for licensed medical professionals. BMJ Publishing Group Ltd (BMJ) does not
advocate or endorse the use of any drug or therapy contained within this publication nor does it diagnose
patients. As a medical professional you retain full responsibility for the care and treatment of your patients
and you should use your own clinical judgement and expertise when using this product.
This content is not intended to cover all possible diagnosis methods, treatments, follow up, drugs and any
contraindications or side effects. In addition, since such standards and practices in medicine change as
new data become available, you should consult a variety of sources. We strongly recommend that you
independently verify specified diagnosis, treatments and follow-up and ensure it is appropriate for your
patient within your region. In addition, with respect to prescription medication, you are advised to check the
product information sheet accompanying each drug to verify conditions of use and identify any changes in
dosage schedule or contraindications, particularly if the drug to be administered is new, infrequently used, or
has a narrow therapeutic range. You must always check that drugs referenced are licensed for the specified
use and at the specified doses in your region.
Information included in BMJ Best Practice is provided on an “as is” basis without any representations,
conditions or warranties that it is accurate and up to date. BMJ and its licensors and licensees assume no
responsibility for any aspect of treatment administered to any patients with the aid of this information. To
the fullest extent permitted by law, BMJ and its licensors and licensees shall not incur any liability, including
without limitation, liability for damages, arising from the content. All conditions, warranties and other terms
which might otherwise be implied by the law including, without limitation, the warranties of satisfactory
quality, fitness for a particular purpose, use of reasonable care and skill and non-infringement of proprietary
rights are excluded.
Where BMJ Best Practice has been translated into a language other than English, BMJ does not warrant the
accuracy and reliability of the translations or the content provided by third parties (including but not limited to
local regulations, clinical guidelines, terminology, drug names and drug dosages). BMJ is not responsible for
any errors and omissions arising from translation and adaptation or otherwise.Where BMJ Best Practice lists
drug names, it does so by recommended International Nonproprietary Names (rINNs) only. It is possible that
certain drug formularies might refer to the same drugs using different names.
Please note that recommended formulations and doses may differ between drug databases drug names and
brands, drug formularies, or locations. A local drug formulary should always be consulted for full prescribing
information.
DISCLAIMER
Treatment recommendations in BMJ Best Practice are specific to patient groups. Care is advised when
selecting the integrated drug formulary as some treatment recommendations are for adults only, and external
links to a paediatric formulary do not necessarily advocate use in children (and vice-versa). Always check
that you have selected the correct drug formulary for your patient.
Where your version of BMJ Best Practice does not integrate with a local drug formulary, you should consult
a local pharmaceutical database for comprehensive drug information including contraindications, drug
interactions, and alternative dosing before prescribing.
Interpretation of numbers
Regardless of the language in which the content is displayed, numerals are displayed according to the
original English-language numerical separator standard. For example 4 digit numbers shall not include a
comma nor a decimal point; numbers of 5 or more digits shall include commas; and numbers stated to be
less than 1 shall be depicted using decimal points. See Figure 1 below for an explanatory table.
BMJ accepts no responsibility for misinterpretation of numbers which comply with this stated numerical
separator standard.
This approach is in line with the guidance of the International Bureau of Weights and Measures Service.
Figure 1 – BMJ Best Practice Numeral Style
105
Chronic congestive heart failure Disclaimer
5-digit numerals: 10,000
4-digit numerals: 1000
numerals < 1: 0.25
Our full website and application terms and conditions can be found here: Website Terms and Conditions.
Contact us
+ 44 (0) 207 111 1105

support@bmj.com
BMJ
BMA House
Tavistock Square
London
WC1H 9JR
UK
DISCLAIMER
Contributors:
// Authors:
Syed Wamique Yusuf, FACC, FRCPI

Professor of Medicine
Department of Cardiology, University of Texas MD Anderson Cancer Center, Houston, TX
DISCLOSURES: SWY declares that he has no competing interests.
// Acknowledgements:
Dr Syed Wamique Yusuf would like to gratefully acknowledge Dr Andrew R.J. Mitchell, Dr Grigorios
Giamouzis, Dr Sonjoy Raja Laskar, and Dr Javed Butler, the previous contributors to this topic. ARJM, GG,
SRL, and JB declare that they have no competing interests.
// Peer Reviewers:
David Leaf, MD, MPH

Professor of Medicine
VA Greater Los Angeles Healthcare System, UCLA School of Medicine, Los Angeles, CA
DISCLOSURES: DL declares that he has no competing interests.
Brian Griffin, MD
Director
Cardiovascular Training Program, Cleveland Clinic, Cleveland, OH
DISCLOSURES: BG declares that he has no competing interests.
Abdallah Al-Mohammad, MD, FRCP(Edin.), FRCP(Lond.)

Consultant Cardiologist and Heart Failure Lead
Sheffield Teaching Hospitals NHS Foundation Trust (Northern General Hospital), Sheffield, UK
DISCLOSURES: AAM has accepted hospitality by NOVARTIS in 2008 to attend the American College of
Cardiology meeting in Chicago, and had received honoraria for delivering educational talks before 2008.
AAM is the co-author of the NICE chronic heart failure partial update of the guideline in 2010, and of several
related articles.

Chronic Congestive Heart Failure

Uploaded by

Copyright:

Available Formats

You might also like

Chronic Congestive Heart Failure

Uploaded by

Document Information

Original Description:

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Chronic Congestive Heart Failure

Uploaded by

Copyright:

Available Formats

Chronic congestive

Straight to the point of care

Last updated: Jun 16, 2021

Based on LVEF, heart failure is defined as follows:[1]

Common causes of chronic heart failure include:

• Coronary artery disease

• Infiltrative diseases: amyloidosis, haemochromatosis, sarcoid

Framingham criteria for the diagnosis of CHF[3]

• Neck vein distension

• Weight loss greater than 4.5 kg in 5 days in response to treatment.

History and exam

neck vein distension (common)

hepatojugular reflux (common)

orthopnoea and parox ysmal nocturnal dyspnoea (uncommon)

chest discomfort (common)

ankle oedema (common)

night cough (common)

fatigue, muscle weakness, or tiredness (common)

palpitations, pre-syncope, or syncope (uncommon)

exposure to cardiotoxic agents

left ventricular dysfunction

left ventricular hypertrophy

valvular heart disease

family history of heart failure

elevated tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6)

elevated C-reactive protein (CRP)

decreased insulin-like growth factor-1 (IGF-1)

elevated natriuretic peptides

dilation of the left ventricle

increased left ventricular mass

abnormal left ventricular diastolic filling

excess alcohol consumption

excess sodium intake

excess coffee consumption

serum electrolytes (including calcium and magnesium) decreased sodium

serum creatinine, blood urea nitrogen normal to elevated

• Reflects abdominal congestion.

blood lipids elevated in dyslipidaemia,

serum ferritin elevated (normal value

Other tests to consider

coronary angiogram coronary artery disease/

underlying presentation and echocardiogram findings.

right heart catheterisation provides objective

serum HIV enzyme-linked immunosorbent assay positive or negative

biomarkers borderline to minimally

Condition Differentiating signs / Differentiating tests

COPD/pulmonary fibrosis • Dyspnoea may be episodic, • Pulmonary function tests

Pneumonia • Patients may present with • CXR may show signs of

fever, cough, and productive consolidation. FBC may

Condition Differentiating signs / Differentiating tests

Post-partum • Patients most commonly • In the presence of raised

Cirrhosis • Typically causes jaundice, • LFTs are abnormal.

Nephrotic syndrome • Typically causes peripheral • Urinalysis shows proteinuria,

Condition Differentiating signs / Differentiating tests

Venous stasis • Oedema affects lower limbs • Doppler examination may

General principles of therapy

Initial drug treatments

Addition of an angiotensin-II receptor antagonist may be considered in persistently symptomatic patients