Buenos Aires 01 de Octubre del 2021



2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure

                      Developed by the Task Force for the diagnosis and treatment of
                      acute and chronic heart failure 
of the European Society of Cardiology (ESC)

                          With the special contribution of the Heart Failure Association (HFA) of the ESC


Authors/Task Force Members:
Theresa McDonagh (Chairperson-United Kingdom), Marco Metra (Chairperson-Italy), Marianna Adamo (Task Force Coordinator-Italy), Roy Gardner (Task Force Coordinator-United Kingdom), Andreas Baumbach (United Kingdom), Michael Bo-(Germany), Haran Burri (Switzerland), Javed Butler (United States of America), Jelena C_elutkiene_(Lithuania), Ovidiu Chioncel (Romania), John G.F. Cleland (United Kingdom), Andrew J.S. Coats (United Kingdom), Maria G. Crespo-Leiro (Spain), Dimitrios Farmakis (Greece), Martine Gilard (France), Stephane Heymans (Netherlands), Arno Hoes (Netherlands), Tiny Jaarsma (Sweden), Ewa A. Jankowska (Poland), Mitja Lainscak (Slovenia), Carolyn S.P. Lam (Singapore), Alexander R. Lyon (United Kingdom), John J.V. McMurray (United Kingdom), Alex Mebazaa (France), Richard Mindham (United Kingdom), Claudio Muneretto (Italy), Massimo Francesco Piepoli (Italy), Susanna Price (United Kingdom), Giuseppe M. Rosano (United Kingdom), Frank Ruschitzka (Switzerland), Anne Kathrine Skibelund (Denmark).

 Chapter 3 – 4 – 17 of 2021 ESC Guidelines


3.1 Definition of heart failure
Heart failure is not a single pathological diagnosis, but a clinical syndrome consisting of cardinal symptoms (e.g. breathlessness, ankle swelling, and fatigue) that may be accompanied by signs (e.g. elevated jugular venous pressure, pulmonary crackles, and peripheral oedema). It is due to a structural and/or functional abnormality of the heart that results in elevated intracardiac pressures and/or inadequate cardiac output at rest and/or during exercise.
Identification of the aetiology of the underlying cardiac dysfunction is mandatory in the diagnosis of HF as the specific pathology can determine subsequent treatment. Most commonly, HF is due to myocardial dysfunction: either systolic, diastolic, or both. However, pathology of the valves, pericardium, and endocardium, and abnormalities of heart rhythm and conduction can also cause or contribute to HF.

3.2 Terminology
3.2.1 Heart failure with preserved, mildly reduced, and reduced ejection fraction
Traditionally, HF has been divided into distinct phenotypes based on the measurement of left ventricular ejection fraction (LVEF). The rationale behind this relates to the original treatment trials in HF that demonstrated substantially improved outcomes in patients with LVEF <_40%. However, HF spans the entire range of LVEF (a normally distributed variable), and measurement by echocardiography is subject to substantial variability.We have decided on the following classification of HF:

  • Reduced LVEF is defined as <_40%, i.e. those with a significant reduction in LV systolic function. This is designated as HFrEF.
  • Patients with a LVEF between 41% and 49% have mildly reduced LV systolic function, i.e. HFmrEF. Retrospective analyses from RCTs in HFrEF or HF with preserved ejection fraction (HFpEF) that have included patients with ejection fractions in the 40_50% range suggest that they may benefit from similar therapies to those with LVEF <_40%. This supports the renaming of HFmrEF from ‘heart failure with mid-range ejection fraction’ to ‘heart failure with mildly reduced ejection fraction’.           
  • Those with symptoms and signs of HF, with evidence of structural and/or functional cardiac abnormalities and/or raised natriuretic peptides (NPs), and with an LVEF >_50%, have HFpEF.

These definitions are consistent with a recent report on the Universal Definition of Heart Failure.
Patients with non-CV disease, e.g. anaemia, pulmonary, renal, thyroid, or hepatic disease may have symptoms and signs very similar to those of HF, but in the absence of cardiac dysfunction, they do not fulfil the criteria for HF. However, these pathologies can coexist with HF and exacerbate the HF syndrome.
3.2.2 Right ventricular dysfunction
Heart failure can also be a result of right ventricular (RV) dysfunction. RV mechanics and function are altered in the setting of either pressure or volume overload. Although the main aetiology of chronic RV failure is LV dysfunction-induced pulmonary hypertension, there are a number of other causes of RV dysfunction [e.g. MI, arrhythmogenic right ventricular cardiomyopathy (ARVC), or valve disease].The diagnosis is determined by a quantitative assessment of global RV function, most commonly by echocardiography, using at least one of the following measurements: fractional area change (FAC); tricuspid annular plane systolic excursion (TAPSE); and Doppler tissue imaging-derived systolic S0 velocity of the tricuspid annulus. The diagnosis and management of RV dysfunction is covered comprehensively in a recent Heart Failure Association (HFA) position paper.
3.2.3 Other common terminology used in heart failure
Heart failure is usually divided into two presentations: chronic heart failure (CHF) and acute heart failure (AHF). CHF describes those who have had an established diagnosis of HF or who have a more gradual onset of symptoms. If CHF deteriorates, either suddenly or slowly, the episode may be described as ‘decompensated’ HF. This can result in a hospital admission or treatment with intravenous (i.v.) diuretic therapy in the outpatient setting. In addition, HF can present more acutely. Both of these are considered in the section on AHF.
Some individuals with HF may recover completely [e.g. those due to alcohol-induced cardiomyopathy (CMP), viral myocarditis,Takotsubo syndrome, peripartum cardiomyopathy  or tachycardiomyopathy]. Other patients with LV systolic dysfunction may show a substantial or even complete recovery of LV systolic function after receiving drug and device therapy.
3.2.4 Terminology related to the symptomatic severity of heart failure
The simplest terminology used to describe the severity of HF is the New York Heart Association (NYHA) functional classification. However, this relies solely on symptoms and there are many other better prognostic indicators in HF Importantly, patients with mild symptoms may still have a high risk of hospitalization and death. Predicting outcome is particularly important in advanced HF to guide selection of cardiac transplantation and device therapies. 

New York Heart Association functional classification based on severity of symptoms and physical activity

  • Class I No limitation of physical activity. Ordinary physical activity does not cause undue breathlessness, fatigue, or palpitations.
  • Class II Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in undue breathlessness, fatigue, or palpitations.
  • Class III Marked limitation of physical activity. Comfortable at rest,but less than ordinary activity results undue breathlessness, fatigue, or palpitations.
  • Class IV Unable to carry on any physical activity without discomfort. Symptoms at rest can be present. If any physical activity is undertaken, discomfort is increased.

3.3 Epidemiology and natural history of heart failure
3.3.1 Incidence and prevalence
In developed countries, the age-adjusted incidence of HF may be falling, presumably reflecting better management of CV disease, but due to ageing, the overall incidence is increasing.Currently, the incidence of HF in Europe is about 3/1000 person-years (all age-groups) or about 5/1000 person-years in adults.The prevalence of HF appears to be 1_2% of adults. As studies only usually include recognized/diagnosed HF cases, the true prevalence is likely to be higher.The prevalence increases with age: from around1% for those aged <55 years to >10% in those aged 70 years or over. It is generally believed that, of those with HF, about 50% have HFrEF and 50% have HFpEF/HFmrEF,mainly based on studies in hospitalized patients.The ESC Long-Term Registry, in the outpatient setting, reports that 60% have HFrEF, 24% have HFmrEF, and 16% have HFpEF. Somewhatmore than 50% of HF patients are female.
3.3.2 Aetiology of heart failure
The aetiology of HF varies according to geography. In Western-type and developed countries, coronary artery disease (CAD) and hypertension are predominant factors. With regard to ischaemic aetiology, HFmrEF resembles HFrEF, with a higher frequency of underlying CAD compared to those with HFpEF.
3.3.3 Natural history and prognosis
The prognosis of patients with HF has improved considerably since the publication of the first treatment trials a few decades ago. However, it remains poor, and quality of life (QOL) is also markedly reduced. The improvement in prognosis has been confined to those with HFrEF.
Mortality rates are higher in observational studies than in clinical trials. In the Olmsted County cohort, 1-year and 5-year mortality rates after diagnosis, for all types of HF patients, were 20% and 53%, respectively, between 2000 and 2010. A study combining the Framingham Heart Study (FHS) and Cardiovascular Health Study (CHS) cohorts reported a 67% mortality rate within 5 years following diagnosis. Despite receiving less evidence-based treatment, women have a better survival thanmen.
Overall prognosis is better in HFmrEF compared to HFrEF. Of note, transition in ejection fraction over time is common, and patients who progress from HFmrEF to HFrEF have a worse prognosis than those who remain stable or transition to a higher ejection fraction category.
HFpEF is generally considered to confer a better survival than HFrEF, but most observational studies show that this difference is negligible. In contrast, the large MAGGIC meta-analysis concluded that the adjusted mortality risk for patients with HFpEF was considerably lower than in patients with HFrEF.
Studies from several countries have shown that between 1980 and 2000 survival in HF patients has improved markedly. However, this positive trend may have levelled off since then. After the initial diagnosis, HF patients are hospitalized once every year on average. From 2000 to 2010, the mean rate of hospitalization in the Olmsted County cohort was 1.3 per person-year. Interestingly, the majority (63%) of hospitalizations were related to non-CV causes. Studies from several European countries and the United States (US) have shown that HF hospitalization rates peaked in the 1990s, and then declined.  However, in a recent study of incident HF conducted between 1998 and 2017 in the United Kingdom (UK), age-adjusted rates of first hospitalizations increased by 28% for both all-cause and HF admissions, and by 42% for non-CV admissions. These increases were higher in women, perhaps related to higher comorbidity rates. The risk of HF hospitalization is 1.5 times higher in patients with diabetes compared to controls. AF, a higher body mass index (BMI), and higher glycated haemoglobin (HbA1c), as well as a low estimated glomerular filtration rate (eGFR) are strong predictors of HF hospitalizations.
Due to population growth, ageing, and the increasing prevalence of comorbidities, the absolute number of hospital admissions for HF is expected to increase considerably in the future, perhaps by as much as 50% in the next 25 years.

Chapter 4

4.1 Key steps in the diagnosis of chronic heart failure
The diagnosis of CHF requires the presence of symptoms and/orsigns of HF and objective evidence of cardiac dysfunction.
Typical symptoms include breathlessness, fatigue and ankle swelling. Symptoms and signs lack sufficient accuracy to be used alone to  make the diagnosis of HF. The diagnosis of CHF is made more likely in patients with a history of MI, arterial hypertension, CAD, diabetes mellitus, alcohol misuse, chronic kidney disease (CKD), cardiotoxic chemotherapy, and in those with a family history of CMP or sudden death.
The following diagnostic tests are recommended for assessment of patients with suspected chronic HF:

(1)   Electrocardiogram (ECG). A normal ECG makes the diagnosis of HF unlikely.The ECG may reveal abnormalities such as AF, Q waves, LV hypertrophy (LVH), and a widened QRS complex  that increase the likelihood of a diagnosis of HF and also may guide therapy.

(2)   Measurement of NPs are recommended, if available.
A plasma concentration of:
         - B-type natriuretic peptide (BNP) <35 pg/m
         - N-terminal pro-B-type natriuretic peptide (NT-proBNP) <125 pg/ mL
         - Mid-regional pro-atrial natriuretic peptide (MR-proANP) <40 pmol/L
Make a diagnosis of HF unlikely.

(3)   Basic investigations such as serum urea, electrolytes, creatinine, full blood count, liver and thyroid function tests are recommended to differentiate HF from other conditions, to provide prognostic information, and to guide potential therapy.

(4)   Echocardiography is recommended as the key investigation for the assessment of cardiac function. As well as the determination of the LVEF, echocardiography also provides information,other parameters such as chamber size, eccentric or concentric LVH, regional wall motion abnormalities (that may suggest underlying CAD, Takotsubo syndrome, or myocarditis), RV function, pulmonary hypertension, valvular function, and markers of diastolic function.

(5)   A chest X-ray is recommended to investigate other potential causes of breathlessness (e.g. pulmonary disease). It may also provide supportive evidence of HF (e.g. pulmonary congestion or cardiomegaly).

4.2 Natriuretic peptides
Plasma concentrations of NPs are recommended as initial diagnostic tests in patients with symptoms suggestive of HF to rule out the diagnosis.
Elevated concentrations support a diagnosis of HF, are useful for prognostication, and may guide further cardiac investigation.
However, it should be noted that there are many causes of an elevatedNP—both CV and non-CV—that might reduce their diagnostic accuracy. These causes include AF, increasing age, and acute or chronic kidney disease. Conversely, NP concentrations may be disproportionately low in obese patients.
Causes of elevated concentrations of natriuretic peptides:

# Cardiac

  • Heart failure
  • ACS
  • Pulmonary embolism
  • Myocarditis
  • Left ventricular hypertrophy
  • Hypertrophic or restrictive cardiomyopathy
  • Valvular heart disease
  • Congenital heart disease
  • Atrial and ventricular tachyarrhythmias
  • Heart contusion
  • Cardioversion, ICD shock
  • Surgical procedures involving the heart
  • Pulmonary hypertension

 # Non-cardiac

  • Advanced age
  • Ischaemic stroke
  • Subarachnoid haemorrhage
  • Renal dysfunction
  • Liver dysfunction (mainly liver cirrhosis with ascites)
  • Paraneoplastic syndrome
  • COPD
  • Severe infections (including pneumonia and sepsis)
  • Severe burns
  • Anaemia
  • Severe metabolic and hormone abnormalities(e.g. thyrotoxicosis, diabetic ketosis)

4.3 Investigations to determine the underlying aetiology of chronic heart failure
Exercise or pharmacological stress echocardiography may be used for the assessment of inducible ischaemia in those who are considered suitable for coronary revascularization. In patients with HFpEF, valve disease, or unexplained dyspnoea, stress echocardiographymight help clarify the diagnosis.
Cardiac magnetic resonance (CMR) imaging with late gadolinium enhancement (LGE), T1 mapping and extracellular volume will identify myocardial fibrosis/scar, which are typically subendocardial for patients with ischaemic heart disease (IHD) in contrast to the mid-wall scar typical of dilated cardiomyopathy (DCM).
In addition, CMR allows myocardial characterization in, e.g. myocarditis, amyloidosis, sarcoidosis, Chagas disease, Fabry disease, LV non-compaction CMP, haemochromatosis, and arrhythmogenic cardiomyopathy (AC).
Computed tomography coronary angiography (CTCA) may be considered in patients with a low to intermediate pre-test probability of CAD, or those with equivocal non-invasive stress tests in order to exclude the diagnosis of CAD.
Single-photon emission CT (SPECT) can also be used to assess myocardial ischaemia and viability, myocardial inflammation or infiltration. Scintigraphy with technetium (Tc)-labelled bisphosphonate has shown high sensitivity and specificity for imaging cardiac transthyretin amyloid.
Coronary angiography is recommended in patients with HF, who have angina pectoris or an ‘angina equivalent’ despite pharmacological therapy, in order to establish the diagnosis of CAD and its severity.
Coronary angiography may also be considered in patients with HFrEF who have an intermediate to high pre-test probability of CAD and who are considered potentially suitable for coronary revascularization.

Chapter 17

17.1 ‘What to do’ and ‘what not to do’ messages from the guidelines

 Recommendations for the diagnosis of chronic HF                           Class - Level                                                                                 

 #   BNP/NT-proBNP.                                                                                         I - B                           #   12-lead ECG.                                                                                             I - C                           #   Transthoracic echocardiography.                                                                  I - C                           #   Routine blood tests for comorbidities (including full blood count, urea
       and electrolytes, thyroid function, fasting glucose and HbA1c, lipids.
       Iron studies (TSAT and ferritin).                                                                  I - C                           #   CMR is recommended for the assessment of myocardial structure and
       function in those with poor echocardiogram  acoustic windows.                      I - C                           #   CMR is recommended for the characterization of myocardial tissue in
       suspected infiltrative disease, Fabry disease, myocarditis, LV
       non-compaction, amyloid, sarcoidosis, iron overload/haemochromatosis.        I - C                          #   Invasive coronary angiography is recommended in patients with angina
       despite pharmacological therapy or symptomatic ventricular arrhythmias.       I - B                            #   Cardiopulmonary exercise testing is recommended, as a  part of the
       evaluation for heart transplantation and/or MCS.                                           I - C                            #   Right heart catheterization is recommended in patients with severe HF
       being evaluated for heart transplantation or MCS.                                          I - C