2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure

3.1 Definition of heart failure

HF is a clinical syndrome characterized by typical 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) caused by a structural and/or functional cardiac abnormality, resulting in a reduced cardiac output and/or elevated intracardiac pressures at rest or during stress.

The current definition of HF restricts itself to stages at which clinical symptoms are apparent. Before clinical symptoms become apparent, patients can present with asymptomatic structural or functional cardiac abnormalities [systolic or diastolic left ventricular (LV) dysfunction], which are precursors of HF. Recognition of these precursors is important because they are related to poor outcomes, and starting treatment at the precursor stage may reduce mortality in patients with asymptomatic systolic LV dysfunction4, 5 (for details see Section 6).

Demonstration of an underlying cardiac cause is central to the diagnosis of HF. This is usually a myocardial abnormality causing systolic and/or diastolic ventricular dysfunction. However, abnormalities of the valves, pericardium, endocardium, heart rhythm and conduction can also cause HF (and more than one abnormality is often present). Identification of the underlying cardiac problem is crucial for therapeutic reasons, as the precise pathology determines the specific treatment used (e.g. valve repair or replacement for valvular disease, specific pharmacological therapy for HF with reduced EF, reduction of heart rate in tachycardiomyopathy, etc).

3.2 Terminology

3.2.1 Heart failure with preserved, mid-range and reduced ejection fraction

The main terminology used to describe HF is historical and is based on measurement of the LVEF. HF comprises a wide range of patients, from those with normal LVEF [typically considered as ≥50%; HF with preserved EF (HFpEF)] to those with reduced LVEF [typically considered as <40%; HF with reduced EF (HFrEF)] (Table 3.1). Patients with an LVEF in the range of 40–49% represent a ‘grey area’, which we now define as HFmrEF (Table 3.1). Differentiation of patients with HF based on LVEF is important due to different underlying aetiologies, demographics, co-morbidities and response to therapies.6 Most clinical trials published after 1990 selected patients based on LVEF [usually measured using echocardiography, a radionuclide technique or cardiac magnetic resonance (CMR)], and it is only in patients with HFrEF that therapies have been shown to reduce both morbidity and mortality.

Table 3.1. Definition of heart failure with preserved (HFpEF), mid-range (HFmrEF) and reduced ejection fraction (HFrEF)

The diagnosis of HFpEF is more challenging than the diagnosis of HFrEF. Patients with HFpEF generally do not have a dilated LV, but instead often have an increase in LV wall thickness and/or increased left atrial (LA) size as a sign of increased filling pressures. Most have additional ‘evidence’ of impaired LV filling or suction capacity, also classified as diastolic dysfunction, which is generally accepted as the likely cause of HF in these patients (hence the term ‘diastolic HF’). However, most patients with HFrEF (previously referred to as ‘systolic HF’) also have diastolic dysfunction, and subtle abnormalities of systolic function have been shown in patients with HFpEF. Hence the preference for stating preserved or reduced LVEF over preserved or reduced ‘systolic function’.

In previous guidelines it was acknowledged that a grey area exists between HFrEF and HFpEF.7 These patients have an LVEF that ranges from 40 to 49%, hence the term HFmrEF. Identifying HFmrEF as a separate group will stimulate research into the underlying characteristics, pathophysiology and treatment of this group of patients. Patients with HFmrEF most probably have primarily mild systolic dysfunction, but with features of diastolic dysfunction (Table 3.1).

Patients without detectable LV myocardial disease may have other cardiovascular causes for HF (e.g. pulmonary hypertension, valvular heart disease, etc.). Patients with non-cardiovascular pathologies (e.g. anaemia, pulmonary, renal or hepatic disease) may have symptoms similar or identical to those of HF and each may complicate or exacerbate the HF syndrome.

3.3 Epidemiology, aetiology and natural history of heart failure

The prevalence of HF depends on the definition applied, but is approximately 1–2% of the adult population in developed countries, rising to ≥10% among people >70 years of age.14-17 Among people >65 years of age presenting to primary care with breathlessness on exertion, one in six will have unrecognized HF (mainly HFpEF).18, 19 The lifetime risk of HF at age 55 years is 33% for men and 28% for women.16 The proportion of patients with HFpEF ranges from 22 to 73%, depending on the definition applied, the clinical setting (primary care, hospital clinic, hospital admission), age and sex of the studied population, previous myocardial infarction and the year of publication.17, 18, 20-30

Data on temporal trends based on hospitalized patients suggest that the incidence of HF may be decreasing, more for HFrEF than for HFpEF.31, 32 HFpEF and HFrEF seem to have different epidemiological and aetiological profiles. Compared with HFrEF, patients with HFpEF are older, more often women and more commonly have a history of hypertension and atrial fibrillation (AF), while a history of myocardial infarction is less common.32, 33 The characteristics of patients with HFmrEF are between those with HFrEF and HFpEF,34 but further studies are needed to better characterize this population.

The aetiology of HF is diverse within and among world regions. There is no agreed single classification system for the causes of HF, with much overlap between potential categories (Table 3.4). Many patients will have several different pathologies—cardiovascular and non-cardiovascular—that conspire to cause HF. Identification of these diverse pathologies should be part of the diagnostic workup, as they may offer specific therapeutic opportunities.

Table 3.4. Aetiologies of heart failure

Many patients with HF and ischaemic heart disease (IHD) have a history of myocardial infarction or revascularization. However, a normal coronary angiogram does not exclude myocardial scar (e.g. by CMR imaging) or impaired coronary microcirculation as alternative evidence for IHD.

In clinical practice, a clear distinction between acquired and inherited cardiomyopathies remains challenging. In most patients with a definite clinical diagnosis of HF, there is no confirmatory role for routine genetic testing, but genetic counselling is recommended in patients with hypertrophic cardiomyopathy (HCM), ‘idiopathic’ DCM or arrhythmogenic right ventricular cardiomyopathy (ARVC) (see Section 5.10.1), since the outcomes of these tests may have clinical implications.

Over the last 30 years, improvements in treatments and their implementation have improved survival and reduced the hospitalization rate in patients with HFrEF, although the outcome often remains unsatisfactory. The most recent European data (ESC-HF pilot study) demonstrate that 12-month all-cause mortality rates for hospitalized and stable/ambulatory HF patients were 17% and 7%, respectively, and the 12-month hospitalization rates were 44% and 32%, respectively.35 In patients with HF (both hospitalized and ambulatory), most deaths are due to cardiovascular causes, mainly sudden death and worsening HF. All-cause mortality is generally higher in HFrEF than HFpEF.35, 36 Hospitalizations are often due to non-cardiovascular causes, particularly in patients with HFpEF. Hospitalization for cardiovascular causes did not change from 2000 to 2010, whereas those with non-cardiovascular causes increased.31

3.4 Prognosis

Estimation of prognosis for morbidity, disability and death helps patients, their families and clinicians decide on the appropriate type and timing of therapies (in particular, decisions about a rapid transition to advanced therapies) and assists with planning of health and social services and resources.

Numerous prognostic markers of death and/or HF hospitalization have been identified in patients with HF (Web Table 3.5). However, their clinical applicability is limited and precise risk stratification in HF remains challenging.

In recent decades, several multivariable prognostic risk scores have been developed for different populations of patients with HF,36-41 and some are available as interactive online applications. Multivariable risk scores may help predict death in patients with HF, but remain less useful for the prediction of subsequent HF hospitalizations.37, 38 A systematic review examining 64 prognostic models37 along with a meta-analysis and meta-regression study of 117 prognostic models38 revealed only a moderate accuracy of models predicting mortality, whereas models designed to predict the combined endpoint of death or hospitalization, or only hospitalization, had an even poorer discriminative ability.

4.1 Symptoms and signs

Symptoms are often non-specific and do not, therefore, help discriminate between HF and other problems (Table 4.1).42-46 Symptoms and signs of HF due to fluid retention may resolve quickly with diuretic therapy. Signs, such as elevated jugular venous pressure and displacement of the apical impulse, may be more specific, but are harder to detect and have poor reproducibility.18, 46, 47 Symptoms and signs may be particularly difficult to identify and interpret in obese individuals, in the elderly and in patients with chronic lung disease.48-50 Younger patients with HF often have a different aetiology, clinical presentation and outcome compared with older patients.51, 52

Table 4.1. Symptoms and signs typical of heart failure

A detailed history should always be obtained. HF is unusual in an individual with no relevant medical history (e.g. a potential cause of cardiac damage), whereas certain features, particularly previous myocardial infarction, greatly increase the likelihood of HF in a patient with appropriate symptoms and signs.42-45

At each visit, symptoms and signs of HF need to be assessed, with particular attention to evidence of congestion. Symptoms and signs are important in monitoring a patient's response to treatment and stability over time. Persistence of symptoms despite treatment usually indicates the need for additional therapy, and worsening of symptoms is a serious development (placing the patient at risk of urgent hospital admission and death) and merits prompt medical attention.

4.2 Essential initial investigations: natriuretic peptides, electrocardiogram and echocardiography

The plasma concentration of natriuretic peptides (NPs) can be used as an initial diagnostic test, especially in the non-acute setting when echocardiography is not immediately available. Elevated NPs help establish an initial working diagnosis, identifying those who require further cardiac investigation; patients with values below the cut-point for the exclusion of important cardiac dysfunction do not require echocardiography (see also Section 4.3 and Section 12). Patients with normal plasma NP concentrations are unlikely to have HF. The upper limit of normal in the non-acute setting for B-type natriuretic peptide (BNP) is 35 pg/mL and for N-terminal pro-BNP (NT-proBNP) it is 125 pg/mL; in the acute setting, higher values should be used [BNP < 100 pg/mL, NT-proBNP < 300 pg/mL and mid-regional pro A-type natriuretic peptide (MR-proANP) < 120 pmol/L]. Diagnostic values apply similarly to HFrEF and HFpEF; on average, values are lower for HFpEF than for HFrEF.54, 55 At the mentioned exclusionary cut-points, the negative predictive values are very similar and high (0.94–0.98) in both the non-acute and acute setting, but the positive predictive values are lower both in the non-acute setting (0.44–0.57) and in the acute setting (0.66–0.67).54, 56-61 Therefore, the use of NPs is recommended for ruling-out HF, but not to establish the diagnosis.

There are numerous cardiovascular and non-cardiovascular causes of elevated NPs that may weaken their diagnostic utility in HF. Among them, AF, age and renal failure are the most important factors impeding the interpretation of NP measurements.55 On the other hand, NP levels may be disproportionally low in obese patients62 (see also Section 12.2 and Table 12.2).

An abnormal electrocardiogram (ECG) increases the likelihood of the diagnosis of HF, but has low specificity.18, 46, 63, 64 Some abnormalities on the ECG provide information on aetiology (e.g. myocardial infarction), and findings on the ECG might provide indications for therapy (e.g. anticoagulation for AF, pacing for bradycardia, CRT if broadened QRS complex) (see Sections 8 and 10). HF is unlikely in patients presenting with a completely normal ECG (sensitivity 89%).43 Therefore, the routine use of an ECG is mainly recommended to rule out HF.

Echocardiography is the most useful, widely available test in patients with suspected HF to establish the diagnosis. It provides immediate information on chamber volumes, ventricular systolic and diastolic function, wall thickness, valve function and pulmonary hypertension.65-74 This information is crucial in establishing the diagnosis and in determining appropriate treatment (see Sections 5.2–5.4 for details on echocardiography).

The information provided by careful clinical evaluation and the above mentioned tests will permit an initial working diagnosis and treatment plan in most patients. Other tests are generally required only if the diagnosis remains uncertain (e.g. if echocardiographic images are suboptimal or an unusual cause of HF is suspected) (for details see Sections 5.5–5.10).

4.3 Algorithm for the diagnosis of heart failure

4.3.1 Algorithm for the diagnosis of heart failure in the non-acute setting

An algorithm for the diagnosis of HF in the non-acute setting is shown in Figure 4.1. The diagnosis of HF in the acute setting is discussed in Section 12.

For patients presenting with symptoms or signs for the first time, non-urgently in primary care or in a hospital outpatient clinic (Table 4.1), the probability of HF should first be evaluated based on the patient's prior clinical history [e.g. coronary artery disease (CAD), arterial hypertension, diuretic use], presenting symptoms (e.g. orthopnoea), physical examination (e.g. bilateral oedema, increased jugular venous pressure, displaced apical beat) and resting ECG. If all elements are normal, HF is highly unlikely and other diagnoses need to be considered. If at least one element is abnormal, plasma NPs should be measured, if available, to identify those who need echocardiography (an echocardiogram is indicated if the NP level is above the exclusion threshold or if circulating NP levels cannot be assessed).55-60, 75-78

5.1 Chest X-ray

A chest X-ray is of limited use in the diagnostic work-up of patients with suspected HF. It is probably most useful in identifying an alternative, pulmonary explanation for a patient's symptoms and signs, i.e. pulmonary malignancy and interstitial pulmonary disease, although computed tomography (CT) of the chest is currently the standard of care. For the diagnosis of asthma or chronic obstructive pulmonary disease (COPD), pulmonary function testing with spirometry is needed. The chest X-ray may, however, show pulmonary venous congestion or oedema in a patient with HF, and is more helpful in the acute setting than in the non-acute setting.49, 64 It is important to note that significant LV dysfunction may be present without cardiomegaly on the chest X-ray.49, 64

5.2 Transthoracic echocardiography

Echocardiography is a term used here to refer to all cardiac ultrasound imaging techniques, including two-dimensional/three-dimensional echocardiography, pulsed and continuous wave Doppler, colour flow Doppler, tissue Doppler imaging (TDI) contrast echocardiography and deformation imaging (strain and strain rate).

Transthoracic echocardiography (TTE) is the method of choice for assessment of myocardial systolic and diastolic function of both left and right ventricles.

5.3 Transoesophageal echocardiography

Transoesophageal echocardiography (TOE) is not needed in the routine diagnostic assessment of HF; however, it may be valuable in some clinical scenarios of patients with valve disease, suspected aortic dissection, suspected endocarditis or congenital heart disease and for ruling out intracavitary thrombi in AF patients requiring cardioversion. When the severity of mitral or aortic valve disease does not match the patient's symptoms using TTE alone, a TOE examination should be performed.

5.4 Stress echocardiography

Exercise or pharmacological stress echocardiography may be used for the assessment of inducible ischaemia and/or myocardium viability99 and in some clinical scenarios of patients with valve disease (e.g. dynamic mitral regurgitation, low-flow–low-gradient aortic stenosis).99, 100 There are also suggestions that stress echocardiography may allow the detection of diastolic dysfunction related to exercise exposure in patients with exertional dyspnoea, preserved LVEF and inconclusive diastolic parameters at rest.85, 86

5.5 Cardiac magnetic resonance

CMR is acknowledged as the gold standard for the measurements of volumes, mass and EF of both the left and right ventricles. It is the best alternative cardiac imaging modality for patients with non-diagnostic echocardiographic studies (particularly for imaging of the right heart) and is the method of choice in patients with complex congenital heart diseases.91, 101, 102

CMR is the preferred imaging method to assess myocardial fibrosis using late gadolinium enhancement (LGE) along with T1 mapping and can be useful for establishing HF aetiology.91, 103 For example, CMR with LGE allows differentiation between ischaemic and non-ischaemic origins of HF and myocardial fibrosis/scars can be visualized. In addition, CMR allows the characterization of myocardial tissue of myocarditis, amyloidosis, sarcoidosis, Chagas disease, Fabry disease non-compaction cardiomyopathy and haemochromatosis.91, 101, 103, 104

CMR may also be used for the assessment of myocardial ischaemia and viability in patients with HF and CAD (considered suitable for coronary revascularization). However, limited evidence from RCTs has failed to show that viability assessed by CMR or other means identified patients who obtained clinical benefit from revascularization.105-107

Clinical limitations of CMR include local expertise, lower availability and higher costs compared with echocardiography, uncertainty about safety in patients with metallic implants (including cardiac devices) and less reliable measurements in patients with tachyarrhythmias. Claustrophobia is an important limitation for CMR. Linear gadolinium-based contrast agents are contraindicated in individuals with a glomerular filtration rate (GFR) <30 mL/min/1.73m², because they may trigger nephrogenic systemic fibrosis (this may be less of a concern with newer cyclic gadolinium-based contrast agents).108

5.6 Single-photon emission computed tomography and radionuclide ventriculography

Single-photon emission CT (SPECT) may be useful in assessing ischaemia and myocardial viability.109 Gated SPECT can also yield information on ventricular volumes and function, but exposes the patient to ionizing radiation. 3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scintigraphy may be useful for the detection of transthyretin cardiac amyloidosis.110

5.7 Positron emission tomography

Positron emission tomography (PET) (alone or with CT) may be used to assess ischaemia and viability, but the flow tracers (N-13 ammonia or O-15 water) require an on-site cyclotron.92, 111 Rubidium is an alternative tracer for ischaemia testing with PET, which can be produced locally at relatively low cost. Limited availability, radiation exposure and cost are the main limitations.

5.8 Coronary angiography

Indications for coronary angiography in patients with HF are in concordance with the recommendations of other relevant ESC guidelines.112-114 Coronary angiography is recommended in patients with HF who suffer from angina pectoris recalcitrant to medical therapy,115 provided the patient is otherwise suitable for coronary revascularization. Coronary angiography is also recommended in patients with a history of symptomatic ventricular arrhythmia or aborted cardiac arrest. Coronary angiography should be considered in patients with HF and intermediate to high pre-test probability of CAD and the presence of ischaemia in non-invasive stress tests in order to establish the ischaemic aetiology and CAD severity.

5.9 Cardiac computed tomography

The main use of cardiac CT in patients with HF is as a non-invasive means to visualize the coronary anatomy in patients with HF with low intermediate pre-test probability of CAD or those with equivocal non-invasive stress tests in order to exclude the diagnosis of CAD, in the absence of relative contraindications. However, the test is only required when its results might affect a therapeutic decision.

The most important clinical indications for the applicability of certain imaging methods in patients with suspected or confirmed HF are shown in the recommendations table.

Recommendations for cardiac imaging in patients with suspected or established heart failure

5.10 Other diagnostic tests

Comprehensive assessment of patients with HF comprises, besides medical history and physical examination, including adequate imaging techniques, a set of additional diagnostic tests, i.e. laboratory variables, ECG, chest X-ray, exercise testing, invasive haemodynamic assessments and endomyocardial biopsy. The major typical indications are summarized in the recommendations table for diagnostic tests in patients with HF. Although there is extensive research on biomarkers in HF (e.g. ST2, galectin 3, copeptin, adrenomedullin), there is no definite evidence to recommend them for clinical practice.

Recommendations for diagnostic tests in patients with heart failure

7.1 Objectives in the management of heart failure

The goals of treatment in patients with HF are to improve their clinical status, functional capacity and quality of life, prevent hospital admission and reduce mortality. The fact that several drugs for HF have shown detrimental effects on long-term outcomes, despite showing beneficial effects on shorter-term surrogate markers, has led regulatory bodies and clinical practice guidelines to seek mortality/morbidity data for approving/recommending therapeutic interventions for HF. However, it is now recognized that preventing HF hospitalization and improving functional capacity are important benefits to be considered if a mortality excess is ruled out.159-161

Figure 7.1 shows a treatment strategy for the use of drugs (and devices) in patients with HFrEF. The recommendations for each treatment are summarized below.

Neuro-hormonal antagonists (ACEIs, MRAs and beta-blockers) have been shown to improve survival in patients with HFrEF and are recommended for the treatment of every patient with HFrEF, unless contraindicated or not tolerated. A new compound (LCZ696) that combines the moieties of an ARB (valsartan) and a neprilysin (NEP) inhibitor (sacubitril) has recently been shown to be superior to an ACEI (enalapril) in reducing the risk of death and of hospitalization for HF in a single trial with strict inclusion/exclusion criteria.162 Sacubitril/valsartan is therefore recommended to replace ACEIs in ambulatory HFrEF patients who remain symptomatic despite optimal therapy and who fit these trial criteria. ARBs have not been consistently proven to reduce mortality in patients with HFrEF and their use should be restricted to patients intolerant of an ACEI or those who take an ACEI but are unable to tolerate an MRA. Ivabradine reduces the elevated heart rate often seen in HFrEF and has also been shown to improve outcomes, and should be considered when appropriate.

The above medications should be used in conjunction with diuretics in patients with symptoms and/or signs of congestion. The use of diuretics should be modulated according to the patient's clinical status.

The key evidence supporting the recommendations in this section is given in Web Table 7.1. The recommended doses of these disease-modifying medications are given in Table 7.2. The recommendations given in Sections 7.5 and 7.6 summarize drugs that should be avoided or used with caution in patients with HFrEF.

Table 7.2. Evidence-based doses of disease-modifying drugs in key randomized trials in heart failure with reduced ejection fraction (or after myocardial infarction)

7.2 Treatments recommended in all symptomatic patients with heart failure with reduced ejection fraction

7.2.1 Angiotensin-converting enzyme inhibitors

ACEIs have been shown to reduce mortality and morbidity in patients with HFrEF2, 5, 163-165 and are recommended unless contraindicated or not tolerated in all symptomatic patients. ACEIs should be up-titrated to the maximum tolerated dose in order to achieve adequate inhibition of the renin–angiotensin–aldosterone system (RAAS). There is evidence that in clinical practice the majority of patients receive suboptimal doses of ACEI.166 ACEIs are also recommended in patients with asymptomatic LV systolic dysfunction to reduce the risk of HF development, HF hospitalization and death (see Section 6).

Pharmacological treatments indicated in patients with symptomatic (NYHA Class II-IV) heart failure with reduced ejection fraction

Practical guidance on how to use ACE inhibitors is given in Web Table 7.4.

7.3 Other treatments recommended in selected symptomatic patients with heart failure with reduced ejection fraction

7.3.1 Diuretics

Diuretics are recommended to reduce the signs and symptoms of congestion in patients with HFrEF, but their effects on mortality and morbidity have not been studied in RCTs. A Cochrane meta-analysis has shown that in patients with chronic HF, loop and thiazide diuretics appear to reduce the risk of death and worsening HF compared with placebo, and compared with an active control, diuretics appear to improve exercise capacity.178, 179

Loop diuretics produce a more intense and shorter diuresis than thiazides, although they act synergistically and the combination may be used to treat resistant oedema. However, adverse effects are more likely and these combinations should only be used with care. The aim of diuretic therapy is to achieve and maintain euvolaemia with the lowest achievable dose. The dose of the diuretic must be adjusted according to the individual needs over time. In selected asymptomatic euvolaemic/hypovolaemic patients, the use of a diuretic drug might be (temporarily) discontinued. Patients can be trained to self-adjust their diuretic dose based on monitoring of symptoms/signs of congestion and daily weight measurements.

Doses of diuretics commonly used to treat HF are provided in Table 7.3. Practical guidance on how to use diuretics is given in Web Table 7.7.

Table 7.3. Doses of diuretics commonly used in patients with heart failure

Other pharmacological treatments recommended in selected patients with symptomatic (NYHA Class II-IV) heart failure with reduced ejection fraction

7.4 Other treatments with less certain benefits in symptomatic patients with heart failure with reduced ejection fraction

This section describes treatments that have shown benefits in terms of symptomatic improvement, reduction in HF hospitalizations or both, and are useful additional treatments in patients with HFrEF.

7.5 Treatments not recommended (unproven benefit) in symptomatic patients with heart failure with reduced ejection fraction

7.5.3 Renin inhibitors

Aliskiren (direct renin inhibitor) failed to improve outcomes for patients hospitalized for HF at 6 months or 12 months in one study208 and is not presently recommended as an alternative to an ACEI or ARB.

Treatments (or combinations of treatments) that may cause harm in patients with symptomatic (NYHA Class II–IV) heart failure with reduced ejection fraction

7.6 Treatments not recommended (believed to cause harm) in symptomatic patients with heart failure with reduced ejection fraction

8.1 Implantable cardioverter-defibrillator

A high proportion of deaths among patients with HF, especially those with milder symptoms, occur suddenly and unexpectedly. Many of these are due to electrical disturbances, including ventricular arrhythmias, bradycardia and asystole, although some are due to coronary, cerebral or aortic vascular events. Treatments that improve or delay the progression of cardiovascular disease will reduce the annual rate of sudden death, but they may have little effect on lifetime risk and will not treat arrhythmic events when they occur. ICDs are effective in preventing bradycardia and correcting potentially lethal ventricular arrhythmias. Some antiarrhythmic drugs might reduce the rate of tachyarrhythmias and sudden death, but they do not reduce overall mortality and may increase it.

Recommendations for implantable cardioverter-defibrillator in patients with heart failure

8.2 Cardiac resynchronization therapy

Recommendations for cardiac resynchronization therapy implantation in patients with heart failure

CRT improves cardiac performance in appropriately selected patients and improves symptoms286 and well-being286 and reduces morbidity and mortality.266 Of the improvement in quality-adjusted life-years (QALYs) with CRT among patients with moderate to severe HF, two-thirds may be attributed to improved quality of life and one-third to increased longevity.287

Only the COMPANION265 and CARE-HF trials262, 263 compared the effect of CRT to guideline-advised medical therapy. Most other trials have compared CRT-D to ICD, and a few have compared CRT-P to backup pacing. The prevention of lethal bradycardia might be an important mechanism of benefit shared by all pacing devices. In CARE-HF, at baseline, 25% of patients had a resting heart rate of ≤60 bpm.262-264 If prevention of bradycardia is important, the effect of CRT will appear greater in trials where there is no device in the control group.

Most studies of CRT have specified that the LVEF should be <35%, but RAFT267 and MADIT-CRT268, 269 specified an LVEF <30%, while REVERSE270-272 specified <40% and BLOCK-HF274 <50%. Relatively few patients with an LVEF of 35–40% have been randomized, but an individual participant data (IPD) meta-analysis suggests no diminution of the effect of CRT in this group.266

Not all patients respond favourably to CRT.286 Several characteristics predict improvement in morbidity and mortality, and the extent of reverse remodelling is one of the most important mechanisms of action of CRT. Patients with ischaemic aetiology will have less improvement in LV function due to myocardial scar tissue, which is less likely to undergo favourable remodelling.288 Conversely, women may be more likely to respond than men, possibly due to smaller body and heart size.273, 285, 289 QRS width predicts CRT response and was the inclusion criterion in all randomized trials. But QRS morphology has also been related to a beneficial response to CRT. Several studies have shown that patients with left bundle branch block (LBBB) morphology are more likely to respond favourably to CRT, whereas there is less certainty about patients with non-LBBB morphology. However, patients with LBBB morphology often have wider QRS duration, and there is a current debate about whether QRS duration or QRS morphology is the main predictor of a beneficial response to CRT. Evidence from two IPD meta-analyses indicates that after accounting for QRS duration, there is little evidence to suggest that QRS morphology or aetiology of disease influence the effect of CRT on morbidity or mortality.266, 273 In addition, none of the landmark trials selected patients for inclusion according to QRS morphology, sex or ischaemic aetiology, nor were they powered for subgroup analyses.

The Echo-CRT283, 284 trial and an IPD meta-analysis266 suggest possible harm from CRT when QRS duration is <130 ms, thus implantation of CRT is not recommended if QRS duration is <130 ms.266, 283, 284

If a patient is scheduled to receive an ICD and is in sinus rhythm with a QRS duration ≥130 ms, CRT-D should be considered if QRS is between 130 and 149 ms and is recommended if QRS is ≥150 ms. However, if the primary reason for implanting a CRT is for the relief of symptoms, then the clinician should choose CRT-P or CRT-D, whichever they consider appropriate. Clinical practice varies widely among countries. The only randomized trial to compare CRT-P and CRT-D265 failed to demonstrate a difference in morbidity or mortality between these technologies.288 If the primary reason for implanting CRT is to improve prognosis, then the majority of evidence lies with CRT-D for patients in NYHA Class II and with CRT-P for patients in NYHA Classes III–IV. It is unclear whether CRT reduces the need for an ICD (by reducing the arrhythmia burden) or increases the benefit from an ICD (by reducing mortality rates from worsening HF, leading to longer exposure to the risk of arrhythmia).

When LVEF is reduced, RV pacing may exacerbate cardiac dyssynchrony. This can be prevented by CRT, which might improve patient outcomes.274, 275, 277, 290 However, a difference in outcome was not observed between CRT and RV pacing in a subgroup analysis of RAFT267 or in patients without HFrEF in BioPACE.291 On balance, CRT rather than RV pacing is recommended for patients with HFrEF regardless of NYHA class who have an indication for ventricular pacing in order to reduce morbidity, although no clear effect on mortality was observed. Patients with HFrEF who have received a conventional pacemaker or an ICD and subsequently develop worsening HF with a high proportion of RV pacing, despite OMT, should be considered for upgrading to CRT.

Only two small trials have compared pharmacological therapy alone vs. CRT in patients with AF, with conflicting results. Several studies have indicated that CRT is superior to RV pacing in patients undergoing atrio-ventricular (AV) node ablation.275, 277, 290 However, CRT is not an indication to carry out AV node ablation except in rare cases when ventricular rate remains persistently high (>110 bpm) despite attempts at pharmacological rate control. A subgroup analysis of patients with AF from the RAFT study found no benefit from CRT-D compared with ICD, although less than half of patients had >90% biventricular capture.276 Observational studies report that when biventricular capture is <98%, the prognosis of patients with CRT declines.277 Whether this association reflects a loss of resynchronization (which might be remedied by device programming), poor placing of the LV lead (which might be avoided at implantation) or greater difficulty in pacing severely diseased myocardium (which might not be amenable to the above) is uncertain. This observation has not been confirmed in a randomized trial.

Imaging tests for dyssynchrony have not yet been shown to be of value in selecting patients for CRT.292 Patients with extensive myocardial scar will have less improvement in LV function with CRT, but this is true of any treatment for HFrEF and does not reliably predict less clinical benefit.293 Pacing thresholds are higher in scarred myocardium and, if possible, lead placement should avoid such regions.294, 295 Although patients with extensive scarring have an intrinsically worse prognosis, there is little evidence that they obtain less prognostic benefit from CRT.266

The reader is directed to guidelines on pacing and CRT for recommendations on device implantation procedures. The value of trying to optimize AV or VV intervals after implantation using echo- or electrocardiographic criteria or blood pressure response is uncertain, but may be considered for patients who have had a disappointing response to CRT.296, 297

8.3 Other implantable electrical devices

For patients with HFrEF who remain symptomatic despite OMT and do not have an indication for CRT, new device therapies have been proposed and in some cases are approved for clinical use in several European Union (EU) countries but remain under trial evaluation.

Cardiac contractility modulation (CCM) is similar in its mode of insertion to CRT, but it involves non-excitatory electrical stimulation of the ventricle during the absolute refractory period to enhance contractile performance without activating extra systolic contractions. CCM has been evaluated in patients with HFrEF in NYHA Classes II–III with normal QRS duration (<120 ms).221, 222 An individual patient data meta-analysis demonstrated an improvement in exercise tolerance (peak VO₂) and quality of life (Minnesota Living with Heart Failure questionnaire). Thus CCM may be considered in selected patients with HF. The effect of CCM on HF morbidity and mortality remains to be established.

Most other devices under evaluation involve some modification of the activity of the autonomic nervous system (ANS) by targeted electrical stimulation.298, 299 These include vagal nerve stimulation, spinal cord stimulation, carotid body ablation and renal denervation, but so far none of the devices has improved symptoms or outcomes in RCTs.

Devices for remote monitoring are discussed in Section 14.

9.1 Effect of treatment on symptoms in heart failure with preserved ejection fraction

Diuretics will usually improve congestion, if present, thereby improving symptoms and signs of HF. The evidence that diuretics improve symptoms is similar across the spectrum of LVEF.178, 179

Evidence that beta-blockers and MRAs improve symptoms in these patients is lacking. There is inconsistent evidence for an improvement in symptoms in those treated with ARBs (only for candesartan was there an improvement in NYHA class)309, 310 and ACEIs.311

9.2 Effect of treatment on hospitalization for heart failure in heart failure with preserved ejection fraction

For patients in sinus rhythm, there is some evidence that nebivolol,173, 312, 313 digoxin,314 spironolactone301 and candesartan310 might reduce HF hospitalizations. For patients in AF, beta-blockers do not appear to be effective and digoxin has not been studied. The evidence in support of either ARBs315 or ACEIs311 is inconclusive.

9.3 Effect of treatment on mortality in heart failure with preserved ejection fraction

Trials of ACEIs, ARBs, beta-blockers and MRAs have all failed to reduce mortality in patients with HFpEF or HFmrEF. However, in older patients with HFrEF, HFpEF or HFmrEF, nebivolol reduced the combined endpoint of death or cardiovascular hospitalization,173, 312 with no significant interaction between treatment effect and baseline LVEF.313

9.4 Other considerations

Patients in AF should receive an anticoagulant to reduce the risk of thromboembolic events (for details, see the ESC guidelines of AF316]. Antiplatelet agents are ineffective for this purpose. Renal dysfunction, which is common in this population, may contraindicate or increase the risk of haemorrhage with NOACs.

The optimal ventricular rate in patients with HFmrEF/HFpEF and AF is uncertain, and aggressive rate control might be deleterious. Whether digoxin, beta-blockers or rate-limiting CCBs, or a combination of these, should be preferred is unknown. Verapamil or diltiazem should not be combined with a beta-blocker. There are insufficient data to recommend ablation strategies (either pulmonary venous or AV node) for HFpEF and HFmrEF.

Circumstantial evidence suggests that treating hypertension, often predominantly systolic, is important in HFmrEF/HFpEF.127, 317 Diuretics, ACEIs, ARBs and MRAs all appear appropriate agents, but beta-blockers may be less effective in reducing SBP. A recent study suggests that patients with hypertension and HFpEF or HFmrEF should not receive an ARB (olmesartan) if they are receiving ACEIs and beta-blockers.318

The first-line oral hypoglycaemic drug for patients with HFpEF and HFmrEF should be metformin319 (see also Section 11.6). Recently, a trial of empagliflozin showed a reduction in blood pressure and body weight, probably by inducing glycosuria and osmotic diuresis. Its use was associated with a reduction in hospitalization for HF and in cardiovascular mortality.130 However, aggressive management of dysglycaemia may be harmful.153, 320

Myocardial ischaemia may contribute to symptoms, morbidity and mortality and should be considered when assessing patients. However, there is only anecdotal evidence that revascularization improves symptoms or outcome. Patients with angina should follow the same management route as patients with HFrEF.112

Patients with HFpEF and HFmrEF have impaired exercise tolerance, commonly accompanied by an augmented blood pressure response to exercise and chronotropic incompetence. Combined endurance/resistance training appears safe for patients with HFpEF and HFmrEF and improves exercise capacity (as reflected by an increase in peak oxygen consumption), physical functioning score and diastolic function.307, 321

Recommendations for treatment of patients with heart failure with preserved ejection fraction and heart failure with mid-range ejection fraction

10.1 Atrial fibrillation

AF is the most common arrhythmia in HF irrespective of concomitant LVEF; it increases the risk of thromboembolic complications (particularly stroke) and may impair cardiac function, leading to worsening symptoms of HF.316 Incident HF precipitated by AF is associated with a more benign prognosis,331 but new-onset AF in a patient with established HF is associated with a worse outcome, probably because it is both a marker of a sicker patient and because it impairs cardiac function.332, 333 Patients with chronic HF and permanent AF have a worse outcome than those in sinus rhythm, although this is largely explained by more advanced age and HF severity.332, 333 Persistent ventricular rates >150 bpm may cause HFrEF that resolves with rate control or rhythm correction (‘tachycardiomyopathy’).334, 335 AF should be classified and managed according to the current AF guidelines (i.e. first diagnosed episode, paroxysmal, persistent, long-standing persistent or permanent), recognizing the uncertainty about the actual duration of the episode and about previous undetected episodes.316

10.1.2 Management of new-onset, rapid atrial fibrillation in patients with heart failure

If the patient has no distressing symptoms of HF, then treatment with oral beta-blockers may be initiated to provide ventricular rate control. For patients with marked congestion who nonetheless have few symptoms at rest, initial treatment with oral or intravenous (i.v.) digoxin is preferred. For patients in haemodynamic instability, an i.v. bolus of digoxin or amiodarone348, 349 should be administered into a peripheral vein with extreme care to avoid extravasation into tissues; where uncertainty exists about venous access, amiodarone must not be given. Longer-term infusion of amiodarone should be given only by central or long-line venous access to avoid peripheral vein phlebitis. In patients with haemodynamic collapse, emergency electrical cardioversion is recommended (see also Section 12).

Recommendations for initial management of a rapid ventricular rate in patients with heart failure and atrial fibrillation in the acute or chronic setting

10.1.4 Rhythm control

In patients with chronic HF, a rhythm control strategy (including pharmacological or electrical cardioversion) has not been shown to be superior to a rate control strategy in reducing mortality or morbidity.359 Urgent cardioversion is indicated only if the AF is life threatening, otherwise both HF and ventricular rate should be controlled prior to cardioversion. A rhythm control strategy is probably best reserved for patients with a reversible secondary cause of AF (e.g. hyperthyroidism) or an obvious precipitant (e.g. recent pneumonia) and in patients with troublesome symptoms due to AF after optimization of rate control and HF therapy. The use of class I antiarrhythmic agents and dronedarone increases morbidity and mortality in patients with HF and AF and should be avoided.246, 247, 347 Amiodarone will cause some patients with chronic AF to revert to sinus rhythm, may reduce symptomatic paroxysms of AF and will help maintain patients in sinus rhythm after spontaneous or electrical cardioversion.343-346 When used, the need for continued administration of amiodarone should be regularly reviewed and justified.

The safety and efficacy of catheter ablation in the atria and pulmonary veins (PV) as a rhythm control strategy in HF is at present uncertain except for tachycardia induced cardiomyopathy.316 One small study suggested that AF ablation was superior to AV node ablation and CRT.360 Another study, including 203 patients with persistent AF, HF and an ICD or CRT device, showed that AF ablation was superior to amiodarone in correcting AF, and this was associated with fewer hospitalizations for HF and lower mortality. Two small studies of AF ablation compared with rate control met with mixed success in terms of procedural complications and success in improving symptoms.278, 279 The most recent evidence from a meta-analysis that included 914 patients suggests an encouraging success rate of PV ablation of AF in patients with LV dysfunction, with improvements in LVEF and functional capacity.361 These results need to be confirmed in ongoing RCTs such as CASTLE AF,362 AMICA and CABANA.

Recommendations for a rhythm control management strategy in patients with atrial fibrillation, symptomatic heart failure (NYHA Class II–IV) and left ventricular systolic dysfunction and no evidence of acute decompensation

10.1.5 Thromboembolism prophylaxis

Patients with HF and AF should generally be anticoagulated and the balance of benefit and risk of bleeding (using CHA₂DS₂-VASc and HAS-BLED scores; for details, please see Web Tables 10.1 and 10.2.) should be evaluated as recommended in the ESC guidelines for AF.316 A substantial proportion of patients with HF will have both benefit and risk scores ≥3, indicating that careful consideration should be given before prescribing an oral anticoagulant and that regular review is subsequently needed (and correctable risk factors for bleeding addressed) if an oral anticoagulant is given.

NOACs are preferred for patients with HF with non-valvular AF, as NOACs compared with vitamin K antagonists seem to be at least similarly effective and even safer (less intracranial haemorrhage) in patients with HF than in subjects without HF,316, 366, 367 although concerns exist about their safety in older patients with HF and poor renal function368, 369 [for a detailed description of the interaction between NOAC and renal function, see Heidbuchel et al.370]. In patients with HF and AF who have mechanical heart valves or at least moderate mitral stenosis, only oral vitamin K antagonists should be used for prevention of thromboembolic stroke.370

The dabigatran dose should be reduced to 110 mg b.i.d. when creatinine clearance is 30–49 mL/min, rivaroxaban to 15 mg daily and edoxaban to 30 mg daily when creatinine clearance is 30–50 mL/min and apixaban to 2.5 mg twice daily if a patient has two or more of the following: age ≥80 years, serum creatinine ≥1.5 mg/dL or body weight ≤60 kg.370-375 The summary of the recommendations for the prevention of thromboembolism in patients with symptomatic HF and paroxysmal or persistent/permanent AF is presented in the recommendations table. For further details, please refer to the recent ESC guidelines on AF.316

A left atrial occlusion device could be considered in a patient with AF as an alternative to an oral anticoagulant who is at high-risk both of thromboembolism and of bleeding in order to avoid the risk of haemorrhage due to anticoagulation risk.381, 382

Recommendations for the prevention of thrombo-embolism in patients with symptomatic heart failure (NYHA Class II–IV) and paroxysmal or persistent/permanent atrial fibrillation

10.2 Ventricular arrhythmias

The initial management of asymptomatic ventricular arrhythmias is correction of electrolyte abnormalities, particularly low serum potassium and magnesium, withdrawal of agents that might provoke arrhythmias and, in patients with HFrEF, optimization of pharmacological therapy with ACEIs, beta-blockers and MRAs and sacubitril/valsartan, which all reduce the risk of sudden death.174, 177, 383, 384

The clinical relevance of myocardial ischaemia for the provocation of ventricular arrhythmias is uncertain, although anecdotal cases of ischaemia-induced arrhythmias exist. Randomized trials of revascularization for patients with HFrEF have not reduced overall mortality,107, 385 even in subgroups of patients with angina or myocardial ischaemia,115, 386 but further analysis did suggest a reduction in sudden deaths.387

Amiodarone (often in combination with a beta-blocker) may be used to suppress symptomatic ventricular arrhythmias, but it may adversely affect prognosis, especially in patients with more severe HF.227, 244 Other antiarrhythmic drugs should be avoided.247 Transcatheter radiofrequency modification of the arrhythmogenic substrate may reduce the number of appropriate ICD discharges and may be used to terminate arrhythmic storm in patients with HF and frequent, recurrent ventricular tachyarrhythmias and therefore should be considered in such patients. Seeking the advice of the members of the HF Team with expertise in electrophysiology is recommended in patients with recalcitrant ventricular arrhythmias. For further details we refer the reader to the ESC/EHRA guidelines on ventricular arrhythmias and sudden cardiac death.260

Recommendations for the management of ventricular tachyarrhythmias in heart failure

10.3 Symptomatic bradycardia, pauses and atrio-ventricular block

The ESC Guidelines on Pacing and CRT recommended intervention when pauses exceed 6 s, even when this is not associated with symptoms.389 However, these recommendations were generated mainly for patients without obvious myocardial dysfunction, and shorter pauses might require intervention in patients with HFrEF.329 If pauses >3 s are identified on electrocardiographic monitoring, medications should be reviewed and the following agents stopped or reduced in dose, starting with rate-limiting CCBs then amiodarone, digoxin and ivabradine. For patients in AF, a reduction in the dose of beta-blockers allowing the daytime resting ventricular rate to rise to 70–90 bpm may be considered, since evidence that beta-blockers improve outcome in patients with AF is lacking.177 For patients with pauses but in sinus rhythm, a reduction in the dose of beta-blockers should be avoided unless the pauses are symptomatic, prolonged or frequent, in which case the relative merits of dose reduction, beta-blocker withdrawal and (biventricular) pacing may be considered. However, evidence is lacking to support a strategy of pacing solely to permit initiation or titration of beta-blocker therapy in the absence of a conventional pacing indication; this strategy is not recommended. For patients with HFrEF and high-degree AV block, CRT is preferred over RV pacing (Section 8.2). When the cause of bradycardia or pauses is sinus node disease with intact AV conduction, then therapeutic strategies that avoid inducing ventricular dyssynchrony are preferred, although clinical trial evidence to support this expert opinion for patients with HF is sparse. For other pacing indications, please consult the ESC Guidelines on Pacing and CRT.389

Recommendations for the management of bradyarrhythmias in heart failure

11.1 Heart failure and co-morbidities

Co-morbidities are of great importance in HF (Table 11.1) and may affect the use of treatments for HF (e.g. it may not be possible to use renin–angiotensin system inhibitors is some patients with severe renal dysfunction) (see Section 7). The drugs used to treat co-morbidities may cause worsening of HF (e.g. NSAIDs given for arthritis, some anti-cancer drugs) (see Section 7). Management of co-morbidities is a key component of the holistic care of patients with HF (see Section 14). Many co-morbidities are actively managed by specialists in the field of the co-morbidity, and these physicians will follow their own specialist guidelines. The current guidelines will identify where the presence of HF should change the way a co-morbidity would normally be treated. This may be because either safety or efficacy may be different in the presence of HF (or may simply be unknown) or because of evidence of particular effects in an HF population, either beneficial or detrimental. HFpEF has an even higher prevalence of co-morbidities compared with HFrEF, and many of these may be instrumental in the progression of this syndrome.398

Table 11.1. Importance of co-morbidities in patients with heart failure

11.2 Angina and coronary artery disease

11.2.2 Myocardial revascularization

For indications for invasive coronary angiography in patients with HF, please refer to Section 5.8.

Percutaneous and surgical revascularization are complementary approaches for symptomatic relief of angina in HFpEF, but whether these interventions improve outcomes is not entirely clear. Recent ESC guidelines on myocardial revascularization recommended coronary artery bypass grafting (CABG) for patients with significant left main stenosis and left main equivalent (proximal stenosis of both the left anterior descending and left circumflex arteries) to improve prognosis.112, 113 However, one needs to be aware of a lack of studies including patients who have well-defined HF, therefore this recommendation is solely based on expert opinion. On the basis of the results of the STICH trial [which excluded patients with left main disease and Canadian Cardiovascular Society (CCS) angina classes III–IV], CABG is also recommended in patients with HFrEF, significant CAD (left anterior descending artery or multivessel disease) and LVEF ≤35% to reduce death and hospitalization for cardiovascular causes.385 Patients with >10% dysfunctional but viable LV myocardium may be more likely to benefit from myocardial revascularization (and those with ≤10% are less likely to benefit), although this approach to patient selection for revascularization is unproven. In the STICH trial, neither the presence of viability nor the severity of LV remodelling identified those who benefited from CABG in terms of a reduction in mortality.118 For the assessment of techniques to assess myocardial viability, please refer to Section 5. Post hoc analyses from the STICH trial revealed that the presence of inducible myocardial ischaemia (either on radionuclide stress test or dobutamine stress echocardiogram) or angina does not identify those with worse prognosis and greater benefit from CABG over OMT.115, 386 However, CABG does improve angina to a greater extent than medical therapy alone.

The choice between CABG and PCI should be made by the Heart Team after careful evaluation of the patient's clinical status and coronary anatomy, expected completeness of revascularization, coexisting valvular disease and co-morbidities.

Recommendations for the treatment of stable angina pectoris with symptomatic (NYHA Class II-IV) heart failure with reduced ejection fraction112, 113

11.3 Cachexia and sarcopenia (for frailty, please refer to Section 14)

Cachexia is a generalized wasting process affecting all body compartments [i.e. lean tissue (skeletal muscle), fat tissue (energy reserves) and bone tissue (osteoporosis)]. It may occur in 5–15% of patients with HF, especially those with HFrEF, and more advanced disease status.414-416 This serious complication is associated with more severe symptoms and reduced functional capacity, more frequent hospitalization and decreased survival. Cachexia in HF can be diagnosed and defined as involuntary non-oedematous weight loss ≥6% of total body weight within the previous 6–12 months.414-417

The causes are multifactorial, and in individual patients they are difficult to determine. These may include pro-inflammatory immune activation, neurohormonal derangements, poor nutrition and malabsorption, impaired calorie and protein balance, anabolic hormone resistance, reduced anabolic drive, prolonged immobilization and physical deconditioning, together characterized by catabolic/anabolic imbalance.418 Skeletal muscle wasting, when associated with impaired mobility and symptoms (termed sarcopenia or myopenia), occurs in 30–50% of patients with HFrEF.419 In its most severe form it is associated with frailty and poor morbidity and mortality.420

Potential treatments may include appetite stimulants, exercise training120 and anabolic agents, including testosterone, in combination with the application of nutritional supplements and anti-catabolic interventions, although none is of proven benefit and their safety is unknown.421

11.4 Cancer

Certain chemotherapeutic agents can cause (or aggravate) LV systolic dysfunction and HF. The best recognized of these are the anthracyclines (e.g. doxorubicin), trastuzumab and tyrosine kinase inhibitors.397, 422 A recent Cochrane review found that dexrazoxane may confer some cardioprotection in patients receiving anthracyclines.423 Pre- and post-evaluation of LVEF, if available with myocardial strain imaging, is essential in patients receiving cardiotoxic chemotherapy, as detailed elsewhere.397, 422 A risk score for identifying women with breast cancer at risk of developing HF during trastuzumab therapy has been developed based on age, chemotherapy details, baseline cardiovascular status and other co-morbidities, and may be helpful.424 Chemotherapy should be discontinued and HFrEF therapy commenced in patients developing moderate to severe LV systolic dysfunction. If LV function improves, the risks and benefits of further chemotherapy need to be reconsidered.397, 425, 426 Mediastinal irradiation can also lead to a variety of long-term cardiac complications. Cardiac biomarkers (NPs and troponins) can be used to identify patients at higher risk of cardiotoxicity and may be helpful in monitoring the use and dosing of cardiotoxic cytotoxics.397, 425, 426

11.5 Central nervous system (including depression, stroke and autonomic dysfunction)

Stroke and HF commonly coexist because of an overlap of shared risk factors. Both contribute to a worse prognosis. Stroke may make self-care more difficult for the HF patient. Management of high-risk stroke patients may require balancing the risk of anticoagulant and antiplatelet therapies.

Autonomic dysfunction is common in HFrEF, especially when severe.427 Combined with low blood pressure, it can make fainting and injuries more likely and can interfere with optimal dosing of beta-blockers, ACEIs, ARBs and MRAs. Diuretic dosage may be reduced to reduce the severity of postural hypotension.

Depression is common and is associated with worse clinical status and a poor prognosis in HF.428-430 It may also contribute to poor adherence and social isolation. A high index of suspicion is needed to make the diagnosis, especially in the elderly. Routine screening using a validated questionnaire is good practice. Until now, the Beck Depression Inventory (BDI) and Cardiac Depression Scale have been formally validated as reliable tools for the assessment of depressive mood in patients with HF,431, 432 but other questionnaires have been broadly used in this group of patients (e.g. Geriatric Depression Scale, Hamilton Depression Scale, Hospital Anxiety and Depression Scale).

Psychosocial intervention and pharmacological treatment are helpful, as well as exercise training, in patients with HFrEF and depression.433 Cognitive behavioural therapy delivered in patients with HF and major depression beyond standard care and a structured education programme were able to reduce depression severity, anxiety and fatigue symptoms, as well as improve social functioning and mental and HF-related quality of life.434

Selective serotonin reuptake inhibitors are thought to be safe, although the Sertraline Antidepressant Heart Attack Randomized Trial did not confirm that sertraline provides a greater reduction in depressive symptoms or improvement in cardiovascular status compared with placebo in HFrEF patients, but this trial was not powered enough to prove the latter.435 Similarly, escitalopram had no effect on either depression or clinical outcomes during the 24-month follow-up as compared with placebo in patients with HFrEF and depression. Importantly, tricyclic antidepressants should be avoided, because they may cause hypotension, worsening HF and arrhythmias.429, 435

11.6 Diabetes

Dysglycaemia and diabetes are very common in HF, and diabetes is associated with poorer functional status and worse prognosis. In patients with HFrEF, interventions that reduce morbidity and mortality confer similar benefit in the presence or absence of diabetes.320 For instance, beta-blockers improve outcome similarly, whether or not the patient has diabetes, although different beta-blockers may vary in their effects on glycaemic indices.436

Whether strict glycaemic control alters the risk of cardiovascular events in patients with HF is uncertain.437 Among patients with HF who have not been treated for diabetes, higher HbA1c is associated with greater risk of cardiovascular events,438, 439 but this may not be the case once treatment for diabetes has been commenced.439

In patients with diabetes and HF, glycaemic control should be implemented gradually and moderately, giving preference to those drugs, such as metformin, that have been shown to be safe and effective. In contrast to what was previously believed, metformin is safe to use in patients with HFrEF, and it should be the treatment of choice in patients with HF440, 441 but is contraindicated in patients with severe renal or hepatic impairment, because of the risk of lactic acidosis.

Insulin is required for patients with type 1 diabetes and to treat symptomatic hyperglycaemia in patients with type 2 diabetes and pancreatic islet β cell exhaustion. However, insulin is a powerful sodium-retaining hormone, and when combined with a reduction in glycosuria, may exacerbate fluid retention, leading to HF worsening. Sulphonylurea derivatives have also been associated with an increased risk of worsening HF and should be used with caution.

Thiazolidinediones (glitazones) cause sodium and water retention and increased risk of worsening HF and hospitalization and are not recommended in patients with HF.209, 210 Dipeptidylpeptidase-4 inhibitors (DPP4is; gliptins), which increase incretin secretion, thereby stimulating insulin release, and long-acting glucagon-like peptide 1 (GLP-1) receptor agonists, which act as incretin mimetics, improve glycaemic indices but do not reduce and may increase the risk of cardiovascular events and worsening HF.320, 442, 443 Importantly, there are no data on the safety of gliptins and GLP-1 analogues in patients with HF.

Recently, empagliflozin, an inhibitor of sodium-glucose co-transporter 2, reduced hospitalization for HF and mortality, but not myocardial infarction or stroke, in patients with diabetes at high cardiovascular risk, some of whom had HF.130 In the absence of other studies with drugs from this group, the results obtained with empaglifozin cannot be considered as a proof of a class effect.

As glycaemic derangement progresses, the judgement on glycaemic control should be made according to cardiac conditions, and if the new anti-diabetic drugs are to be prescribed, they have to be closely monitored by an HF team.

11.7 Erectile dysfunction

Erectile dysfunction is a common and important component of quality of life in men with HF.444, 445 Its treatment should include optimal therapies for underlying cardiovascular diseases and other interfering co-morbidities (e.g. diabetes) and amelioration of anxiety and depressive symptoms. Some drugs applied for HF therapy (e.g. thiazide diuretics, spironolactone and beta-blockers) may augment erectile dysfunction.444, 445 Phosphodiesterase type 5 inhibitors (PDE5Is) have been shown to have favourable haemodynamic and anti-remodelling effects and to improve exercise capacity and quality of life in patients with HFrEF,446, 447 but they are contraindicated in patients taking nitrates.

11.8 Gout and arthritis

Hyperuricaemia and gout are common in HF and may be caused or aggravated by diuretic treatment. Hyperuricaemia is associated with a worse prognosis in HFrEF.448 The current European League Against Rheumatism (EULAR) guideline for the management of gout recommends that urate-lowering therapy (ULT) is indicated in patients with recurrent acute flares, arthropathy, tophi or radiographic changes of gout, aiming to maintain a serum urate level below the saturation point for monosodium urate [<357 μmol/L (<6 mg/dL)].449

Xanthine oxidase inhibitors (allopurinol, oxypurinol) may be used to prevent gout, although their safety in HFrEF is uncertain.450 Gout attacks are better treated with colchicine rather than with NSAIDs (although colchicine should not be used in patients with very severe renal dysfunction and may cause diarrhoea). Intra-articular corticosteroids are an alternative for monoarticular gout, but systemic corticosteroids cause sodium and water retention.

Arthritis is a common co-morbidity and is a common cause of both self-taken and prescribed drugs that can worsen renal function and HF, especially NSAIDs. Rheumatoid arthritis is associated with an increased risk of HFpEF. The safety of disease-modifying drugs commonly given to patients with rheumatoid arthritis has not been established in HF.

11.9 Hypokalaemia and hyperkalaemia

Both hypokalaemia and hyperkalaemia are associated with HF and with many drugs used for HF treatment.451 Both can aggravate ventricular arrhythmias.

Loop and thiazide diuretics reduce serum potassium, while ACEIs, ARBs and MRAs can all increase serum potassium. Amiloride and triamterene are sometimes used as adjunct diuretics in resistant oedema and to assist in preventing hypokalaemia. The treatment of hypokalaemia can involve recommending high potassium foods or prescribing potassium supplements.

The management of acute hyperkalaemia (>6.0 mmol/L) may require a short-term cessation of potassium-retaining agents and RAAS inhibitors, but this should be minimized and RAAS inhibitors should be carefully reintroduced as soon as possible while monitoring potassium levels. A Cochrane review452 found no trial evidence of major outcome benefits for any emergency therapy regimen for hyperkalaemia. Two new potassium binders (patiromer and sodium zirconium cyclosilicate) are currently under consideration for regulatory approval.453, 454 Initial results from patients with HF are available and confirm the efficacy of these therapies in reducing serum potassium455 and preventing recurrent hyperkalaemia in patients with HF and CKD in the context of treatment with RAAS inhibitors.456

11.10 Hyperlipidaemia

Elevated low-density lipoprotein cholesterol is uncommon in HFrEF; patients with advanced HFrEF often have low concentrations of low-density lipoprotein, which is associated with a worse prognosis. Rosuvastatin did not reduce the primary composite mortality/morbidity endpoints in two large RCTs in patients with HF with or without IHD, but it also did not increase risk, and may have reduced, hospitalizations.205, 457 Therefore there is no evidence to recommend the initiation of statins in most patients with HF. However, in patients who are already receiving a statin for CAD, a continuation of this therapy may be considered.

11.11 Hypertension

Hypertension is associated with an increased risk of developing HF; antihypertensive therapy markedly reduces the incidence of HF (with an exception of α-adrenoceptor blockers, which are less effective than other antihypertensives in preventing HF).458 A recent prospective cohort study documented that in a population with incident HF, higher baseline systolic, diastolic and pulse pressure levels were associated with a higher rate of adverse events, which further supports the importance for optimized blood pressure control in this population.459 Blood pressure control is an element of the holistic management of patients with HF.

Negatively inotropic CCBs (i.e. diltiazem and verapamil) should not be used to treat hypertension in patients with HFrEF (but are believed to be safe in HFpEF), and moxonidine should also be avoided in patients with HFrEF, as it increased mortality in patients in one RCT.460 If blood pressure is not controlled with an ACEI (or an ARB), a beta-blocker, an MRA and a diuretic, then hydralazine and amlodipine215 [or felodipine216] are additional blood pressure lowering agents that have been shown to be safe in systolic HF. The blood pressure targets recommended in hypertension guidelines317 are applicable to HF. Uncontrolled hypertension in patients with HFrEF is very rare, provided they are optimally treated for HF. In contrast, treatment of hypertension is an important issue in patients with HFpEF. In patients with AHF, i.v. nitrates (or sodium nitroprusside) are recommended to lower blood pressure (see Section 12).

Recommendations for the treatment of hypertension in patients with symptomatic (NYHA Class II-IV) heart failure with reduced ejection fraction

11.12 Iron deficiency and anaemia

Iron deficiency is common in HF, as it is with other chronic illnesses, and it can lead to anaemia and/or skeletal muscle dysfunction without anaemia.466 Within an HF population, iron deficiency is associated with a worse prognosis.467, 468 Intravenous iron has been specifically studied in two RCTs in patients with HF and iron deficiency (serum ferritin <100 µg/L or ferritin between 100 and 299 µg/L and transferrin saturation <20%)469, 470 both with and without anaemia. Intravenous ferric carboxymaltose (FCM) has been shown to improve self-reported patient global assessment, quality of life and NYHA class (over 6 months) in the FAIR-HF trial469 both in anaemic and non-anaemic patients with HF,471 and in the CONFIRM-HF trial470, exercise capacity improved over 24 weeks. In the analysis of secondary endpoints in the CONFIRM-HF trial, i.v. iron reduced the risk of HF hospitalizations in iron-deficient patients with HFrEF.470 A meta-analysis of i.v. iron therapy in HFrEF patients with iron deficiency over up to 52 weeks showed reduced hospitalization rates and improved HF symptoms, exercise capacity and quality of life.472 Treatment with FCM may therefore result in sustainable improvement in functional capacity, symptoms and quality of life. Treatment was also associated with a significant reduction in hospitalizations for worsening HF. The number of deaths and the incidence of adverse events were similar. Neither i.v. iron trial was powered to test for an effect on major outcomes or to evaluate separately the effects in anaemic and non-anaemic patients. The effect of treating iron deficiency in HFpEF/HFmrEF and the long-term safety of iron therapy in either HFrEF, HFmrEF or HFpEF is unknown. The safety of i.v. iron is unknown in patients with HF and haemoglobin >15 g/dL.469, 470 Patients with iron deficiency need to be screened for any potentially treatable/reversible causes (e.g. gastrointestinal sources of bleeding).

Recommendations for the treatment of other co-morbidities in patients with heart failure

Treatments not recommended of other co-morbidities in patients with heart failure

Anaemia (defined as a haemoglobin concentration <13.0 g/dL in men and <12.0 g/dL in women) is common in HF, particularly in hospitalized patients. It is more common in women, the elderly and in patients with renal impairment and is associated with advanced myocardial remodelling, inflammation and volume overload.474 Anaemia is associated with advanced symptoms, worse functional status, greater risk of HF hospitalization and reduced survival. A diagnostic workup to seek a cause for any finding of anaemia is indicated (e.g. occult blood loss, iron deficiency, B12/folate deficiency, blood dyscrasias), although in many patients no specific cause is found. The erythropoietin-stimulating agent darbepoetin alfa did not improve clinical outcomes in HFrEF patients with mild to moderate anaemia, but led to an excess of thromboembolic events and is therefore not recommended.475

11.13 Kidney dysfunction (including chronic kidney disease, acute kidney injury, cardio-renal syndrome and prostatic obstruction)

HF and CKD frequently coexist, share many risk factors (diabetes, hypertension, hyperlipidaemia) and interact to worsen prognosis.476, 477 CKD is generally defined as an eGFR <60 mL/min/1.73 m² and/or the presence of albuminuria (high 30–300 or very high >300 mg albumin/1 g of urine creatinine). Patients with severe renal dysfunction (eGFR <30 mL/min/1.73m²) have systematically been excluded from randomized clinical trials and therefore there is lack of evidence-based therapies in these patients.

A further deterioration in renal function, termed worsening renal function (WRF), is used to indicate an increase in serum creatinine, usually by >26.5 µmol/L (0.3 mg/dL) and/or a 25% increase or a 20% drop in GFR. The importance of these apparently small changes is that they are frequent, they promote the development and progression of CKD478 and, as a consequence, can worsen the prognosis of HF. Increases in creatinine during an AHF hospitalization are not always clinically relevant, especially when they are accompanied by appropriate decongestion, diuresis and haemoconcentration.479

Large increases in serum creatinine, termed acute kidney injury (AKI), are relatively rare in HF and are probably associated with the combination of diuretic therapy with other potentially nephrotoxic drugs such as some antibiotics (gentamicin and trimethoprim), contrast media, ACEIs, ARBs, NSAIDs, etc. Of relevance, some of these drugs may accumulate if they are renally excreted. In HF, WRF is relatively common, especially during initiation and up-titration of RAAS inhibitor therapy. Despite the fact that RAAS blockers can frequently cause a decrease in GFR in patients with HF, this reduction is usually small and should not lead to treatment discontinuation unless there is a marked decrease, as the treatment benefit in these patients is probably largely maintained.480 When large increases in serum creatinine occur, care should be taken to evaluate the patient thoroughly and should include assessment of a possible renal artery stenosis, excessive hyper- or hypovolaemia, concomitant medication and hyperkalaemia, which frequently coincides with WRF.

Diuretics, especially thiazides, but also loop diuretics, may be less effective in patients with a very low GFR, and if used, should be dosed appropriately (higher doses to achieve similar effects). Renally excreted drugs (e.g. digoxin, insulin and low molecular weight heparin) may accumulate in patients with renal impairment and may need dose adjustment if renal function deteriorates. Patients with HF and coronary or peripheral vascular disease are at risk of acute renal dysfunction when they undergo contrast media enhanced angiography [contrast-induced acute kidney injury (CI-AKI)]. Renal dysfunction and worsening renal function is further discussed in the section about AHF (see Section 12).

Prostatic obstruction is common in older men and can interfere with renal function; it should therefore be ruled out in men with HF with deteriorating renal function. α-adrenoceptor blockers cause hypotension and sodium and water retention, and may not be safe in HFrEF.458, 464, 465 For these reasons, 5-α-reductase inhibitors are generally preferred in the medical treatment of prostatic obstruction in patients with HF.

11.14 Lung disease (including asthma and chronic obstructive pulmonary disease)

The diagnosis of COPD and asthma may be difficult in patients with HF, due to overlap in symptoms and signs, but also problems in the interpretation of spirometry, especially in HFpEF.48, 49, 391 COPD (and asthma) in patients with HF may be overdiagnosed.481 Spirometry should be performed when patients have been stable and euvolaemic for at least 3 months, to avoid the confounding effect of pulmonary congestion causing external obstruction of alveoli and bronchioles.482 Both correctly and incorrectly labelled COPD are associated with worse functional status and a worse prognosis in HFrEF.

Beta-blockers are only relatively contraindicated in asthma, but not in COPD, although a more selective β1-adrenoceptor antagonist (i.e. bisoprolol, metoprolol succinate, or nebivolol) is preferred.48, 49, 391 The contraindication to beta-blockers in asthma, as mentioned on pharmacy leaflets, is based on small case series published in the 1980s and late 1990s with very high initial dosages in young patients with severe asthma. In clinical practice, starting with low doses of cardioselective beta-blockers combined with close monitoring for signs of airway obstruction (wheezing, shortness of breath with lengthening of the expiration) may allow the use of profoundly effective beta-blockers in HFrEF, especially in older people where true severe asthma is uncommon. Therefore, according to the 2015 GINA global strategy report,395, 396 asthma is not an absolute contraindication, but these medications should only be used under close medical supervision by a specialist, with consideration of the risks for and against their use. The long-term safety of cardioactive inhaled pulmonary drugs is uncertain and the need for their use should be reconsidered in patients with HFrEF, especially as their benefit in asthma and COPD may be symptomatic only without a clear effect on mortality. Oral corticosteroids can cause sodium and water retention, potentially leading to worsening of HF, but this is not believed to be a problem with inhaled corticosteroids. Pulmonary hypertension can complicate severe long-standing COPD, which, as a result, makes right-sided HF and congestion more likely. Non-invasive ventilation, added to conventional therapy, improves the outcome of patients with acute respiratory failure due to hypercapnic exacerbation of COPD or HF in situations of acute pulmonary oedema.

11.15 Obesity

Obesity is a risk factor for HF141 and complicates its diagnosis, because it can cause dyspnoea, exercise intolerance and ankle swelling and may result in poor-quality echocardiographic images. Obese individuals also have reduced NP levels.62 Obesity is more common in HFpEF than in HFrEF, although it is possible that misdiagnosis may explain at least some of this difference in prevalence. Although obesity is an independent risk factor for developing HF, once HF is diagnosed, it is well established that obesity is associated with lower mortality across a wide range of body mass indexes (BMIs) (see also cachexia in Section 11.3)—the so-called obesity paradox also seen in other chronic illnesses.414, 416 Obesity should be managed as recommended in the ESC guidelines on cardiovascular disease prevention,483 if the aim is to prevent future development of HF. However, these guidelines do not refer to the HF patient in whom higher BMI is not adverse, and, although often recommended for symptom benefit and risk factor control, weight loss as an intervention has never been prospectively shown to be either beneficial or safe in HFrEF. When weight loss is occurring in HF, it is associated with high mortality and morbidity, worse symptom status and poor quality of life. In patients with HF with moderate degrees of obesity (BMI <35 kg/m²), weight loss cannot be recommended. In more advanced obesity (BMI 35–45 kg/m²), weight loss may be considered to manage symptoms and exercise capacity.

11.16 Sleep disturbance and sleep-disordered breathing

Sleep-disordered breathing (SDB) occurs in more than one-third of patients with HF,484 being even more prevalent in patients with AHF.485 The most common types are: central sleep apnoea (CSA, similar to Cheyne Stokes respiration, CSR), obstructive sleep apnoea (OSA), and a mixed pattern of the two. Other causes of sleep disturbance include anxiety, depression, decubitus or paroxysmal pulmonary congestion (orthopnoea and paroxysmal nocturnal dyspnoea) and diuretic therapy causing nocturnal diuresis. Reviewing sleep history (including asking a partner) is part of the holistic care of patients with HF (see Section 14). CSA and OSA have been shown to be associated with a worse prognosis in HF.485, 486 OSA is associated with an increased risk of incident HF in men.487 CSA is the most common form of SDB in HFrEF, and HFrEF is the most common cause of CSA, so they are closely linked. Screening for, and the diagnosis and treatment of, sleep apnoea is discussed in detail elsewhere.484, 488 Diagnosis used to require overnight polysomnography, although advanced home testing equipment which can distinguish the type of sleep apnoea has been developed.

Nocturnal oxygen supplementation, continuous positive airway pressure (CPAP), bi-level positive airway pressure (BiPAP), and adaptive servo-ventilation (ASV) may be considered to treat nocturnal hypoxaemia in OSA as recommended in other guidelines.489, 490 An apnoea/hypopnoea index (AHI) of above 30 per hour can be treated using any of CPAP, BiPAP, ASV and nocturnal oxygen supplementation, which have all been shown to be effective in this regard. It should be noted, however, that none of these interventions has been prospectively shown to be beneficial on major outcomes in HFrEF.

CPAP in HF related CSA has been shown to reduce the frequency of episodes of apnoea and hypopnoea, and improve LVEF and 6 minute walk test distance, but did not improve prognosis or the rate of HF related hospitalizations.491

The recently published SERVE-HF473 trial has shown that ASV used in patients with HFrEF and a predominantly CSA was neutral regarding the composite primary endpoint (all-cause death, lifesaving cardiovascular intervention, i.e. cardiac transplantation, implantation of a ventricular assist device, resuscitation after sudden cardiac arrest, or appropriate lifesaving shock, or unplanned hospitalization for HF worsening), but more importantly led to an increase in both all-cause and cardiovascular mortality. Therefore ASV is not recommended in patients with HFrEF and predominantly CSA.

The safety and efficacy of alternative approaches to treating CSA in HFrEF patients, such as implantable phrenic nerve stimulation,219, 220, 492 are presently undergoing clinical investigation and may require additional long term study.

11.17 Valvular heart disease

Valvular heart disease may cause or aggravate HF. This section briefly addresses problems particularly relevant to HF, and the reader is referred to the recent guidelines on valvular disease for more information.493, 494

Patients with HF and concomitant valvular heart disease constitute a high-risk population. Thus, the whole process of decision-making through a comprehensive evaluation of the risk–benefit ratio of different treatment strategies should be made by a multidisciplinary ‘heart team’ with a particular expertise in valvular heart disease, including cardiologists with expertise in HF, cardiac surgeons, a structural valve interventionist if a catheter-based therapy is being considered, imaging specialists, anaesthetists and, if needed, general practitioners, geriatricians, or intensive care specialists. This may be particularly beneficial in patients with HF being considered for surgery, transcatheter aortic valve implantation or transcatheter mitral valve intervention.

All patients should receive OMT. In those with HFrEF pharmacological therapy should be planned according to a previously described algorithm (see Section 7 for details). Care must be taken using vasodilators (ACEI, ARBs, CCBs, hydralazine, and nitrates) in patients with severe aortic stenosis in order not to cause hypotension.

11.17.4 Tricuspid regurgitation

Secondary (functional) tricuspid regurgitation (TR) frequently complicates the natural course of HF, due to annular dilatation and increased tricuspid leaflet tethering in relation to RV pressure and/or volume overload. Severe TR causes/deteriorates symptoms and signs of right HF, thus diuretics are used to reduce peripheral oedema. As hepatic congestion is often present in these patients (additionally contributing to hyperaldosteronism), an addition of an MRA (in higher natriuretic doses) may improve decongestion.507 Management of HF which underlies secondary TR should be optimized as TR may diminish, following the treatment of its cause. Indications for surgical correction of secondary TR complicating HF are not clearly established.493, 494 The need for correction of TR is usually considered at the time of surgical correction of left-sided valve lesions.493, 494 A recent first report indicated that catheter-based interventions may be possible for TR.508

Recommendations for treatment of valvular diseases in patients with heart failure

12.1 Definition and classification

AHF refers to rapid onset or worsening of symptoms and/or signs of HF. It is a life-threatening medical condition requiring urgent evaluation and treatment, typically leading to urgent hospital admission.

AHF may present as a first occurrence (de novo) or, more frequently, as a consequence of acute decompensation of chronic HF, and may be caused by primary cardiac dysfunction or precipitated by extrinsic factors, often in patients with chronic HF. Acute myocardial dysfunction (ischaemic, inflammatory or toxic), acute valve insufficiency or pericardial tamponade are among the most frequent acute primary cardiac causes of AHF. Decompensation of chronic HF can occur without known precipitant factors, but more often with one or more factors, such as infection, uncontrolled hypertension, rhythm disturbances or non-adherence with drugs/diet (Table 12.1).

Table 12.1. Factors triggering acute heart failure

A large number of overlapping classifications of AHF based on different criteria have been proposed.510-513 In practice the most useful classifications are those based on clinical presentation at admission, allowing clinicians to identify patients at high risk of complications and to direct management at specific targets, which creates a pathway for personalized care in the AHF setting. In most cases, patients with AHF present with either preserved (90–140 mmHg) or elevated (>140 mmHg; hypertensive AHF) systolic blood pressure (SBP). Only 5–8% of all patients present with low SBP (i.e. <90 mmHg; hypotensive AHF), which is associated with poor prognosis, particularly when hypoperfusion is also present.514, 515

Another approach is to classify patients according to the presence of the following precipitants/causes leading to decompensation, which need to be treated/corrected urgently (see Section 12.3.1): ACS, hypertensive emergency, rapid arrhythmias or severe bradycardia/conduction disturbance, acute mechanical cause underlying AHF or acute pulmonary embolism.

Clinical classification can be based on bedside physical examination in order to detect the presence of clinical symptoms/signs of congestion (‘wet’ vs. ‘dry’ if present vs. absent) and/or peripheral hypoperfusion (‘cold’ vs. ‘warm’ if present vs. absent) (Figure 12.1).514, 515 The combination of these options identifies four groups: warm and wet (well perfused and congested) —most commonly present; cold and wet (hypoperfused and congested); cold and dry (hypoperfused without congestion); and warm and dry (compensated, well perfused without congestion). This classification may be helpful to guide therapy in the initial phase and carries prognostic information.510, 514, 515

Patients with HF complicating AMI can be classified according to Killip and Kimball13 into class I, no clinical signs of HF; class II, HF with rales and S₃ gallop; class III, with frank acute pulmonary oedema; class IV, cardiogenic shock, hypotension (SBP <90 mmHg) and evidence of peripheral vasoconstriction such as oliguria, cyanosis and diaphoresis.

Definitions of the terms used in this section related to clinical presentation of patients with AHF are provided in Table 12.2.

Table 12.2. Definitions of the terms used in Section 12 on acute heart failure

12.2 Diagnosis and initial prognostic evaluation

The diagnostic workup needs to be started in the pre-hospital setting and continued in the emergency department (ED) in order to establish the diagnosis in a timely manner and initiate appropriate management. The greater benefit of early treatment is well established in ACS and now needs to be considered in the setting of AHF.516, 517 In parallel, coexisting life-threatening clinical conditions and/or precipitants that require urgent treatment/correction need to be immediately identified and managed (Figure 12.2). Typically, an initial step in the diagnostic workup of AHF is to rule out alternative causes for the patient's symptoms and signs (i.e. pulmonary infection, severe anaemia, acute renal failure).

When AHF is confirmed clinical evaluation is mandatory to select further management.

It is recommended that initial diagnosis of AHF should be based on a thorough history assessing symptoms, prior cardiovascular history and potential cardiac and non-cardiac precipitants, as well as on the assessment of signs/symptoms of congestion and/or hypoperfusion by physical examination and further confirmed by appropriate additional investigations such as ECG, chest X-ray, laboratory assessment (with specific biomarkers) and echocardiography.

In patients presenting with AHF, early initiation of appropriate therapy (along with relevant investigations) is of key importance.516-518

Table 12.3. Causes of elevated concentrations of natriuretic peptides^522–524

Numerous clinical and laboratory variables are independent predictors of in-hospital complications and longer-term outcomes in AHF syndromes, but their impact on management has not been adequately established.

Recommendations regarding applied diagnostic measurements

12.3 Management

AHF is a life-threatening medical condition, thus rapid transfer to the nearest hospital should be pursued, preferably to a site with a cardiology department and/or a coronary care/intensive care unit (CCU/ICU).

Early diagnosis is important in AHF. Therefore, all patients with suspected AHF should have a diagnostic workup and appropriate pharmacological and non-pharmacological treatment should be started promptly and in parallel.

Initial evaluation and continued non-invasive monitoring of the patient's vital cardiorespiratory functions, including pulse oximetry, blood pressure, respiratory rate and a continuous ECG instituted within minutes, is essential to evaluate whether ventilation, peripheral perfusion, oxygenation, heart rate and blood pressure are adequate. Urine output should also be monitored, although routine urinary catheterization is not recommended.

Patients with respiratory distress/failure or haemodynamic compromise should be triaged to a location where immediate respiratory and cardiovascular support can be provided (Figure 12.2).

12.3.3 Management of the early phase

Oxygen therapy and/or ventilatory support

Recommendations for the management of patients with acute heart failure: oxygen therapy and ventilatory support

In AHF, oxygen should not be used routinely in non-hypoxaemic patients, as it causes vasoconstriction and a reduction in cardiac output.546, 547 In COPD, hyperoxygenation may increase ventilation–perfusion mismatch, suppressing ventilation and leading to hypercapnia. During oxygen therapy, acid–base balance and transcutaneous SpO₂ should be monitored.

Non-invasive positive pressure ventilation includes both CPAP and bi-level positive pressure ventilation (PPV). Bi-level PPV also allows inspiratory pressure support that improves minute ventilation and is especially useful in patients with hypercapnia, most typically COPD patients.

Congestion affects lung function and increases intrapulmonary shunting, resulting in hypoxaemia. The fraction of inspired oxygen (FiO₂) should be increased up to 100% if necessary, according to SpO₂, unless contraindicated. Hyperoxia, however, should be avoided.546, 547 Non-invasive positive pressure ventilation reduces respiratory distress541-545 and may decrease intubation and mortality rates,543 although data regarding mortality are less conclusive. CPAP is a feasible technique in the pre-hospital setting, because it is simpler than pressure support positive end-expiratory pressure (PS-PEEP) and requires minimal training and equipment. On hospital arrival, patients who still show signs of respiratory distress should continue with non-invasive ventilation, preferably PS-PEEP, in case of acidosis and hypercapnia, particularly in those with a previous history of COPD or signs of fatigue.540

Caution should be exercised with regard to side effects of anaesthetic drugs, among which propofol can induce hypotension and have cardiodepressive side effects. In contrast, midazolam may have fewer cardiac side effects and thus is preferred in patients with AHF or cardiogenic shock.

A management algorithm for patients with AHF based on the clinical profile during an early phase is presented in Figure 12.3.

Pharmacological therapy

Recommendations for the management of patients with acute heart failure: pharmacotherapy

Diuretics

Diuretics are a cornerstone in the treatment of patients with AHF and signs of fluid overload and congestion. Diuretics increase renal salt and water excretion and have some vasodilatory effect. In patients with AHF and signs of hypoperfusion, diuretics should be avoided before adequate perfusion is attained.

The initial approach to congestion management involves i.v. diuretics with the addition of vasodilators for dyspnoea relief if blood pressure allows. To enhance diuresis or overcome diuretic resistance, options include dual nephron blockade by loop diuretics (i.e. furosemide or torasemide) with thiazide diuretics or natriuretic doses of MRAs.570, 571 However, this combination requires careful monitoring to avoid hypokalaemia, renal dysfunction and hypovolaemia.

Data defining optimal dosing, timing and method of delivery are incomplete. In the ‘high-dose’ arm of the DOSE study, administration of furosemide at 2.5 times the previous oral dose resulted in greater improvement in dyspnoea, larger weight change and fluid loss at the cost of transient worsening in renal function.548 In AHF, i.v. furosemide is the most commonly used first-line diuretic. The dose should be limited to the smallest amount to provide adequate clinical effect and modified according to previous renal function and previous dose of diuretics. The initial i.v. dose should be at least equal to the pre-existing oral dose used at home. Consequently, patients with new-onset AHF or those with chronic HF without a history of renal failure and previous use of diuretics may respond to i.v. boluses of 20–40 mg, whereas those with previous use of diuretics usually require higher doses. A bolus of 10–20 mg i.v. torasemide may be considered as an alternative.

Vasodilators

Intravenous vasodilators (Table 12.4) are the second most often used agents in AHF for symptomatic relief; however, there is no robust evidence confirming their beneficial effects.

Table 12.4. Intravenous vasodilators used to treat acute heart failure

They have dual benefit by decreasing venous tone (to optimize preload) and arterial tone (decrease afterload). Consequently, they may also increase stroke volume. Vasodilators are especially useful in patients with hypertensive AHF, whereas in those with SBP <90 mmHg (or with symptomatic hypotension) they should be avoided. Dosing should be carefully controlled to avoid excessive decreases in blood pressure, which is related to poor outcome. Vasodilators should be used with caution in patients with significant mitral or aortic stenosis.

Use of an inotrope (Table 12.5) should be reserved for patients with a severe reduction in cardiac output resulting in compromised vital organ perfusion, which occurs most often in hypotensive AHF. Inotropic agents are not recommended in cases of hypotensive AHF where the underlying cause is hypovolaemia or other potentially correctable factors before elimination of these causes. Levosimendan is preferable over dobutamine to reverse the effect of beta-blockade if beta-blockade is thought to be contributing to hypoperfusion.572 However, levosimendan is a vasodilator, thus it is not suitable for treatment of patients with hypotension (SBP <85 mmHg) or cardiogenic shock unless in combination with other inotropes or vasopressors.559, 573, 574 Inotropes, especially those with adrenergic mechanisms, can cause sinus tachycardia and may induce myocardial ischaemia and arrhythmias, thus ECG monitoring is required. There is long-standing concern that they may increase mortality, which derives from studies in which intermittent or continuous infusions of inotropes were given.559-563, 575 In any case, inotropes have to be used with caution starting from rather low doses and up-titrating with close monitoring.

Table 12.5. Positive inotropes and/or vasopressors used to treat acute heart failure

Vasopressors

Drugs with prominent peripheral arterial vasoconstrictor action such as norepinephrine or dopamine in higher doses (>5 μg/kg/min) are given to patients with marked hypotension. These agents are given to raise blood pressure and redistribute blood to the vital organs. However, this is at the expense of an increase in LV afterload.

Dopamine was compared with norepinephrine in the treatment of various shock patients. A subgroup analysis suggested that norepinephrine would have fewer side effects and lower mortality.558 Epinephrine (adrenaline) should be restricted to patients with persistent hypotension despite adequate cardiac filling pressures and the use of other vasoactive agents, as well as for resuscitation protocols.576

Thromboembolism prophylaxis

Thromboembolism prophylaxis with heparin or another anticoagulant is recommended unless contraindicated or unnecessary (because of existing treatment with oral anticoagulants).

Digoxin

Digoxin is mostly indicated in patients with AF and rapid ventricular rate (>110 bpm) and given in boluses of 0.25–0.5 mg i.v. if not used previously (0.0625–0.125 mg may be an adequate dose in patients with moderate to severe renal dysfunction). However, in patients with co-morbidities or other factors affecting digoxin metabolism (including other drugs) and/or the elderly, the maintenance dose may be difficult to estimate theoretically, and in this situation it should be established empirically, based on the measurements of digoxin concentration in peripheral blood.

Vasopressin antagonists

Vasopressin antagonists such as tolvaptan block the action of arginine vasopressin (AVP) at the V₂ receptor in renal tubules and promote aquaresis. Tolvaptan may be used to treat patients with volume overload and resistant hyponatraemia (thirst and dehydration are recognized adverse effects).577

Opiates

Opiates relieve dyspnoea and anxiety. In AHF, routine use of opiates is not recommended and they may only be cautiously considered in patients with severe dyspnoea, mostly with pulmonary oedema. Dose-dependent side effects include nausea, hypotension, bradycardia and respiratory depression (potentially increasing the need for invasive ventilation). There are controversies regarding the potentially elevated mortality risk in patients receiving morphine.568, 569

Anxiolytics and sedatives

Anxiolytics or sedatives may be needed in a patient with agitation or delirium. Cautious use of benzodiazepines (diazepam or lorazepam) may be the safest approach.

Device therapy

Recommendations regarding renal replacement therapy in patients with acute heart failure

Renal replacement therapy

Ultrafiltration involves the removal of plasma water across a semipermeable membrane in response to a transmembrane pressure gradient. There is no evidence favouring ultrafiltration over loop diuretics as first-line therapy in patients with AHF.571, 578 At the present time, routine use of ultrafiltration is not recommended and should be confined to patients who fail to respond to diuretic-based strategies.

The following criteria may indicate the need for initiation of renal replacement therapy in patients with refractory volume overload: oliguria unresponsive to fluid resuscitation measures, severe hyperkalaemia (K⁺ >6.5 mmol/L), severe acidaemia (pH <7.2), serum urea level >25 mmol/L (150 mg/dL) and serum creatinine >300 µmol/L (>3.4 mg/dL).

Mechanical assist devices

Intra-aortic balloon pump

The conventional indications for an intra-aortic balloon pump (IABP) are to support the circulation before surgical correction of specific acute mechanical problems (e.g. interventricular septal rupture and acute mitral regurgitation), during severe acute myocarditis and in selected patients with acute myocardial ischaemia or infarction before, during and after percutaneous or surgical revascularization. There is no good evidence that an IABP is of benefit in other causes of cardiogenic shock (for details see below).

Ventricular assist devices

Ventricular assist devices and other forms of mechanical circulatory support (MCS) may be used as a ‘bridge to decision’ or longer term in selected patients (see Section 13).

Other interventions

In patients with AHF and pleural effusion, pleurocentesis with fluid evacuation may be considered if feasible in order to alleviate dyspnoea.

In patients with ascites, ascitic paracentesis with fluid evacuation may be considered in order to alleviate symptoms. This procedure, through reduction in intra-abdominal pressure, may also partially normalize the transrenal pressure gradient, thus improving renal filtration.581

12.3.4 Management of patients with cardiogenic shock

Cardiogenic shock is defined as hypotension (SBP <90 mmHg) despite adequate filling status with signs of hypoperfusion (Table 12.1). The pathogenetic scenarios of cardiogenic shock range from low-output advanced end-stage chronic HF to acute-onset de novo cardiogenic shock most often caused by STEMI, but also by various aetiologies other than ACS. A patient in cardiogenic shock should undergo immediate comprehensive assessment. ECG and echocardiography are required immediately in all patients with suspected cardiogenic shock. In patients with cardiogenic shock complicating ACS, an immediate coronary angiography is recommended (within 2 h from hospital admission) with an intent to perform coronary revascularization.114, 535 Invasive monitoring with an arterial line should be also considered.

There is no agreement on the optimal method of haemodynamic monitoring in assessing and treating patients in cardiogenic shock, including pulmonary artery catheterization.

Pharmacologic therapy aims to improve organ perfusion by increasing cardiac output and blood pressure. After fluid challenge, pharmacologic management consists of an inotropic agent and a vasopressor as needed. Treatment is guided by the continuous monitoring of organ perfusion and haemodynamics. Pulmonary artery catheterization may be considered. As a vasopressor, norepinephrine is recommended when mean arterial pressure needs pharmacologic support. Dobutamine is the most commonly used adrenergic inotrope. Levosimendan may also be used in combination with a vasopressor.582, 583 Levosimendan infusion in cardiogenic shock following AMI on top of dobutamine and norepinephrine improved cardiovascular haemodynamics without leading to hypotension.582, 583 PDE3 inhibitors may be another option, especially in non-ischaemic patients.561, 584

However, rather than combining several inotropes, device therapy has to be considered when there is an inadequate response. Recently the IABP-SHOCK II trial showed that the use of an IABP did not improve outcomes in patients suffering from AMI and cardiogenic shock.585, 586 Therefore, routine use of an IABP cannot be recommended.

Recommendations regarding management of patients with cardiogenic shock

12.4 Management of evidence-based oral therapies

Recommendations regarding oral evidence-based disease-modifying therapies in patients with acute heart failure

Oral disease-modifying HF therapy should be continued on admission with AHF, except in the presence of haemodynamic instability (symptomatic hypotension, hypoperfusion, bradycardia), hyperkalaemia or severely impaired renal function. In these cases, the daily dosage of oral therapy may be reduced or stopped temporarily until the patient is stabilized. In particular, beta-blockers can be safely continued during AHF presentations except in cardiogenic shock. A recent meta-analysis demonstrated that discontinuation of beta-blockers in patients hospitalized with AHF was associated with significantly increased in-hospital mortality, short-term mortality and the combined endpoint of short-term rehospitalization or mortality.587

12.5 Monitoring of clinical status of patients hospitalized due to acute heart failure

Recommendations regarding monitoring of clinical status of patients hospitalized due to acute heart failure

Patients should be weighed daily and an accurate fluid balance chart should be maintained. Renal function should preferably be monitored with daily measurement of BUN/urea, creatinine and electrolytes. Routine use of a urinary catheter is not recommended.

Renal function is commonly impaired at admission, but may improve or deteriorate with diuresis. Routine monitoring of pulse, respiratory rate and blood pressure should continue. There is no study showing the usefulness of invasive haemodynamic monitoring in patients with AHF excluding those with cardiogenic shock. There is evidence that measuring NPs during the hospital admission may help with discharge planning. Patients whose NP concentrations fall during admission have lower cardiovascular mortality and readmission rates at 6 months.588-590

12.6 Criteria for discharge from hospital and follow-up in high-risk period

12.7 Goals of treatment during the different stages of management of acute heart failure

During the treatment of patients with AHF, one can distinguish subsequent stages that require different therapeutic approaches (described in the previous sections of this chapter). Importantly, the goals of treatment during the different stages of management of patients with AHF also differ, and are summarized in Table 12.6.

Table 12.6. Goals of treatment in acute heart failure

13.1 Mechanical circulatory support

For patients with either chronic or acute HF who cannot be stabilized with medical therapy, MCS systems can be used to unload the failing ventricle and maintain sufficient end-organ perfusion. Patients in acute cardiogenic shock are initially treated with short-term assistance using extracorporeal, non-durable life support systems so that more definitive therapy may be planned. Patients with chronic, refractory HF despite medical therapy can be treated with a permanent implantable left ventricular assist device (LVAD). Table 13.1 lists the current indications for the use of mechanical circulatory assist devices.593

Table 13.1. Terms describing various indications for mechanical circulatory support

13.1.2 Mechanical circulatory support in end-stage chronic heart failure

Heart transplantation has always been a limited therapeutic option for patients with end-stage chronic HF. The increasing number of patients with refractory, chronic HF and the declining willingness for organ donation have resulted in expanded waiting lists and prolonged waiting times for patients listed for heart transplantation (median 16 months in the region covered by Eurotransplant).598 More than 60% of patients are transplanted in high-urgency status, leaving little chance for patients listed for less urgent transplantation. Three times more patients are listed for heart transplantation annually than are actually transplanted, and the mortality rate on the Eurotransplant waiting list in 2013 was 21.7%.598

More recent data suggest that patients with ongoing LVAD support may have an improved survival on the transplant waiting list.599 Accordingly, MCS devices, particularly continuous-flow LVADs, are increasingly seen as an alternative to heart transplantation. Initially LVADs were developed for use as a short-term BTT approach (Table 12.6),600 but they are now being used for months to years in patients who will either face a long-term wait on the transplant list (currently only 10% of patients with an MCS device implanted with a BTT indication will receive an organ within 1 year of listing) or in patients who are not eligible for transplantation as permanent therapy or destination therapy. The number of patients with a permanent LVAD who are considered neither too old nor ineligible for transplantation is constantly growing. For a majority of these patients, lifelong LVAD therapy, despite eligibility for transplantation, has become a clinical reality. Current 2–3-year survival rates in carefully selected patients receiving the latest continuous flow devices are excellent, and comparable to early survival after heart transplantation.595 However, fewer data are available for longer-term outcomes. Among patients with continuous-flow LVADs, actuarial survival is 80% at 1 year and 70% at 2 years in predominantly non-transplant-eligible patients. Notably, survival of 85% at 2 years was recorded for patients up to 70 years of age without diabetes, renal impairment or cardiogenic shock.601, 602 Patients receiving LVAD devices as BTT have a post-transplant survival rate similar or better than those not requiring or receiving bridging.599 Despite technological improvements, bleeding, thromboembolism (both of which can cause stroke), pump thrombosis, driveline infections and device failure remain significant problems and affect the long-term outcome of patients on MCS.599, 603-606 It is recommended that such devices should only be implanted and managed at centres with appropriately trained specialist HF physicians and surgeons and an outpatient LVAD clinic with trained nursing staff.607

In some patients, LV reverse remodelling and functional improvement during MCS may permit removal of the LVAD [‘bridge to recovery’ (BTR)]. This outcome is more likely in younger patients with an acute fulminant but reversible cause of HF, such as acute myocarditis or peripartum cardiomyopathy.608, 609 LVADs may also be used as a ‘bridge to candidacy’ (BTC) in order to permit recovery of end-organ dysfunction, improve RV function and relieve pulmonary hypertension, which may allow initially ineligible patients to become eligible for heart transplantation.

Earlier ventricular assist device (VAD) implantation in less severely ill patients, e.g. those not yet on inotropic support, was tested in a recent trial that revealed better outcomes than in those patients continuing on medical therapy.605 The INTERMACS registry likewise shows better outcomes in patients implanted with a higher INTERMACS class, although the majority of VAD implants are done at INTERMACS levels 1–3.604, 610 Additionally, it needs to be remembered that no RCTs exist comparing medical therapy vs. MCS devices in these transplant-eligible patients (Table 13.2).

Table 13.2. INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) stages for classifying patients with advanced heart failure

Typically, patients with end-stage HF considered for MCS exhibit many clinical hallmarks of declining cardiovascular function593 and may already be on continuous inotropic support or manifest a decline in end-organ function. Markers of liver and renal dysfunction, haematologic and coagulation abnormalities and lower serum albumin levels are associated with worse outcome.611, 612

Evaluation of RV function is crucial since postoperative RV failure greatly increases perioperative mortality and reduces survival to, and after, transplantation. There are, however, multiple approaches to assessment of the RV (see Section 5.2.3). If RV failure is expected to be potentially reversible, temporary (days to weeks) extracorporeal right ventricular assist device (RVAD) support using a centrifugal pump in addition to LVAD implantation may be considered. For patients with chronic biventricular failure or a high risk for persisting RV failure after LVAD implantation, implantation of a biventricular assist device (BiVAD) may be necessary. Patients requiring long-term BiVAD support must be transplant-eligible, as BiVAD therapy is not suitable for destination therapy. The outcomes of BiVAD therapy are inferior to those for LVAD therapy and therefore the indication for VAD therapy should be discussed before RV function deteriorates. The implantation of a total artificial heart with removal of the native heart should be restricted to selected patients who cannot be treated with an LVAD (unrepairable ventricular septal defect, cardiac rupture).

Patients with active infection, severe renal, pulmonary or hepatic dysfunction or uncertain neurological status after cardiac arrest or due to cardiogenic shock are not usually candidates for BTT or DT but may be candidates for BTC (Table 13.3).

Table 13.3. Patients potentially eligible for implantation of a left ventricular assist device

Recommendations for implantation of mechanical circulatory support in patients with refractory heart failure

13.2 Heart transplantation

Heart transplantation is an accepted treatment for end-stage HF.614, 615 Although controlled trials have never been conducted, there is a consensus that transplantation—provided that proper selection criteria are applied—significantly increases survival, exercise capacity, quality of life and return to work compared with conventional treatment.

Apart from the shortage of donor hearts, the main challenges in transplantation are the consequences of the limited effectiveness and complications of immunosuppressive therapy in the long term (i.e. antibody-mediated rejection, infection, hypertension, renal failure, malignancy and coronary artery vasculopathy). The indications for and contraindications to heart transplantation have recently been updated and are summarized in Table 13.4.616 It needs to be considered that some contraindications are transient and treatable. While an active infection remains a relative contraindication to heart transplantation, patients with HIV, hepatitis, Chagas disease and tuberculosis can be considered as suitable candidates provided certain strict management principles are adhered to by the teams. In patients with cancer requiring heart transplantation, a close collaboration with oncology specialists should occur to stratify each patient as to their risk of tumour recurrence.616

Table 13.4. Heart transplantation: indications and contra-indications

The use of mechanical circulatory support, particularly LVAD, should be considered for patients with potentially reversible or treatable co-morbidities, such as cancer, obesity, renal failure, tobacco use and pharmacologically irreversible pulmonary hypertension, with a subsequent re-evaluation to establish candidacy.

14.1 Organization of care

The goal of management of HF is to provide a ‘seamless’ system of care that embraces both the community and hospital throughout the health care journey. The standards of care that patients with HF should expect have been published by the ESC HFA.591 To achieve this goal, other services, such as cardiac rehabilitation and palliative care, must be integrated into the overall provision for patients with HF. Fundamental to the delivery of this complete package of care are multidisciplinary management programmes designed to improve outcomes through structured follow-up with patient education, optimization of medical treatment, psychosocial support and improved access to care (Table 14.1). Such strategies reduce HF hospitalization and mortality in patients discharged from the hospital.624, 625

Key to the success of these programmes is coordination of care along the continuum of HF and throughout the chain of care delivered by the various services within the health care system. This necessitates close collaboration between HF practitioners (primarily cardiologists, HF nurses and general practitioners) and other experts, including pharmacists, dieticians, physiotherapists, psychologists, palliative care providers and social workers. The content and structure of HF management programmes may vary in different countries and health care settings. The components shown in Table 14.1 are recommended. HF services should be easily accessible to the patient and his/her family and care providers. A telephone helpline may facilitate access to professional advice.

The website http://ww.heartfailurematters.org is an option for professional information for those patients and families with Internet access.

14.2 Discharge planning

Early readmission after hospital discharge is common and may be addressed through coordinated discharge planning. The standards of care that patients should expect have been published by the HFA and the Acute Cardiac Care Association.540, 631 Discharge planning should commence as soon as the patient's condition is stable. During hospital admission, providing patients with information and education for self-care improves outcome. Discharge should be arranged for when the patient is euvolaemic and any precipitants of the admission have been treated. Hospitals with early physician follow-up after discharge show reduced 30-day readmission, and those that initiated programmes to discharge patients with an outpatient follow-up appointment already scheduled experienced a greater reduction in readmissions than those not taking up this strategy.632

14.3 Lifestyle advice

There is little evidence that specific lifestyle advice improves quality of life or prognosis; however, providing this information has become a key component of education for self-care. Patients should be provided with sufficient up-to-date information to make decisions on lifestyle adjustment and self-care. Ideally for those patients admitted to the hospital, lifestyle advice should begin prior to discharge. Information should be individually tailored to need and take into account relevant co-morbidities that may influence retention of information (such as cognitive impairment and depression). Practical recommendations have been published by the HFA.591 Key topics to include are recommended in Table 14.2.

14.4 Exercise training

Several systematic reviews and meta-analyses of small studies have shown that physical conditioning by exercise training improves exercise tolerance, health-related quality of life and HF hospitalization rates in patients with HF. A single large RCT618 showed a modest and non-significant reduction in the primary composite outcome of all-cause mortality or all-cause hospitalization. There was no reduction in mortality and no safety concerns were raised.618, 633 The most recent Cochrane review of exercise training619 included 33 trials with 4740 patients with HF (predominantly HFrEF). There was a trend towards a reduction in mortality with exercise in trials with >1 year of follow-up. Compared with the control group, exercise training reduced the rate of overall and HF-specific hospitalization and improved quality of life. Practical recommendations on exercise training have been published by the HFA.120

There is evidence that in patients with HFpEF, exercise training has several benefits, including improvements in exercise capacity, as measured objectively using peak oxygen consumption, quality of life and diastolic function, assessed by echocardiography.321, 620, 621, 634

Patients with HF, regardless of LVEF, are recommended to perform properly designed exercise training (see the recommendations table).

14.5 Follow-up and monitoring

Patients with HF benefit from regular follow-up and monitoring of biomedical parameters to ensure the safety and optimal dosing of medicines and detect the development of complications or disease progression that may require a change in management (e.g. the onset of AF or development of anaemia). Monitoring may be undertaken by the patients themselves during home visits, in community or hospital clinics, by remote monitoring with or without implanted devices or by structured telephone support (STS). The optimal method of monitoring will depend on local organizations and resources and will vary among patients. For example, more frequent monitoring will be required during periods of instability or optimization of medication. Older adults may also benefit from more frequent monitoring. Some patients will be keen and able to participate in self-monitoring.

High circulating NPs predict unfavourable outcomes in patients with HF, and a decrease in NP levels during recovery from circulatory decompensation is associated with a better prognosis.588-590 Although it is plausible to monitor clinical status and tailor treatment based on changes in circulating NPs in patients with HF, published studies have provided differing results.635-638 This does not enable us to recommend a broad application of such an approach.

Telemedicine in HF, which is also termed remote patient management, has variable clinical trial results.639 Several meta-analyses suggest clinical benefits, but numerous prospectively initiated clinical trials including >3700 patients have not confirmed this. These clinical trials include Tele-HF,640 TIM-HF,641 INH,642 WISH643 and TEHAF.644 It is clear that there is not just one type of telemedicine, and each approach needs to be assessed on its individual merit.

Recently, two individual approaches were shown to be successful in improving clinical outcome when used in patients with HFpEF or HFrEF. These approaches include the CardioMems system (tested in 550 patients with both HFrEF and HFpEF)628 and the IN-TIME approach (tested in 664 HFrEF patients)630, which may be considered for use in selected patients with HF (see the recommendations table).

14.6 The older adult, frailty and cognitive impairment

HF management and self-care behaviour are complicated by ageing, co-morbid conditions, cognitive impairment, frailty and limited social support. HF is also a leading cause of hospital admission in the older adult, where it is associated with increased hospital length of stay and risk of mortality.645

Frailty is common in older adults with HF, with a recent study suggesting it may be present in >70% of patients with HF and >80 years of age.645 Frailty scoring systems provide an objective assessment and identify the presence of or change in the level of frailty. Patients with a high frailty score will benefit from closer contact with the HF specialist team, more frequent follow-up and monitoring and individualized self-care support.

Frailty scores include646 walking speed (gait speed test), timed up-and-go test, PRISMA 7 questionnaire, Frail Score,647 Fried Score647, 648 and Short Physical Performance Battery (SPPB).

Cognitive impairment and HF frequently coexist. Acute delirium is also associated with decompensated HF and may be present on hospital admission. Cognitive function can be assessed using the Mini-Mental State Examination649 or the Montreal cognitive assessment.650 The presence of delirium and HF is found more commonly in older adults and is associated with increased mortality and poorer self-care ability and increases any hospital length of stay.651 There is currently no clinical evidence that HF medication worsens or improves cognitive function. However, its effect on HF outcome suggests such medication should be used. Support from a multidisciplinary HF team in collaboration with specialist dementia support teams, alongside medication compliance aids, tailored self-care advice and involvement of family and caregivers, may improve adherence with complex HF medication and self-care regimens (see Table 14.2 on patient education) (Table 14.3).

Table 14.3. Specific recommendations regarding monitoring and follow-up of the older adult with heart failure

14.7 Palliative and end-of-life care

Palliative care approaches include a focus on symptom management, emotional support and communication between the patient and his/her family. Ideally this should be introduced early in the disease trajectory and increased as the disease progresses. A decision to alter the focus of care from modifying disease progression to optimising quality of life should be made in discussion with the patient, cardiologist, nurse and general practitioner. The patient's family should be involved in such discussions if requested by the patient652, 653 (Table 14.4).

Table 14.4. Patients with heart failure in whom end of life care should be considered

Key components of a palliative care service are recommended in Table 14.5. Palliative care has been discussed in detail in a position paper from the ESC HFA.654

Table 14.5. Key components of palliative care service in patients with heart failure

Liaison between the specialist palliative care services and the HF team and/or the primary care physician, using a shared care approach, is required in order to address and optimally coordinate the patient's care. Recent pilot studies have suggested an improvement in symptom burden and quality of life,653, 655 but these data are too limited to provide a recommendation.

Palliative outcome scores include the Palliative Care Outcome Scale,657 Karnofsky Performance Status658 and Functional Assessment of Chronic Illness Therapy – Palliative Care (FACIT-Pal).659