Evidence categories (Ia-IV) and recommendation grades (A-C) are defined at the end of the Major Recommendations field.
In addition to evidence-based recommendations, the guideline development group (GDG) also identifies good practice points (GPP) as well as evidence from diagnostic studies (DS) and from the National Institute for Clinical Excellence (NICE) guidelines or health technology appraisal programme (NICE).
Diagnosing Heart Failure
The full evaluation of heart failure is more than stating whether the syndrome is present or not; it requires consideration of the underlying abnormality of the heart, the severity of the syndrome, the aetiology, precipitating and exacerbating factors, identification of concomitant disease relevant to the management, and an estimation of prognosis. It is important to exclude other conditions that may masquerade as heart failure (see below and Table 2 in the full version of the original guideline document).
Other Conditions That May Present with Similar Symptoms
- Obesity
- Chest disease – including lung, diaphragm, or chest wall
- Venous insufficiency in lower limbs
- Drug-induced ankle swelling (e.g., dihydropyridine calcium channel blockers)
- Drug-induced fluid retention (e.g., nonsteroidal anti-inflammatory drugs [NSAIDs])
- Hypoalbuminaemia
- Intrinsic renal or hepatic disease
- Pulmonary embolic disease
- Depression and/or anxiety disorders
- Severe anaemia or thyroid disease
- Bilateral renal artery stenosis
*Elderly patients are likely to have a number of concomitant medical problems.
Cardiac Assessment
GPP - Take a careful and detailed history and perform a clinical examination. These should be combined with tests to confirm the presence of heart failure and make a complete diagnosis.
B - Health care professionals should seek to exclude a diagnosis of heart failure through the following investigations:
- 12-lead electrocardiography (ECG)
- and/or natriuretic peptides (B-type natriuretic peptide [BNP] or N-terminal pro-B-type natriuretic peptide [NTproBNP]) – where available
If one or both are abnormal, a diagnosis of heart failure cannot be excluded and transthoracic Doppler 2-dimensional (2D) echocardiography should be performed because it consolidates the diagnosis and provides information on the underlying functional abnormality of the heart.
GPP - Efforts should be made to exclude other disorders that may present in a similar manner.
GPP – To evaluate possible aggravating factors and/or alternative diagnoses the following tests are recommended.
- Chest x-ray
- Blood tests:
- Biochemical profile including electrolytes, urea, and creatinine
- Full blood count
- Thyroid function tests
- Liver function tests
- Fasting lipids
- Fasting glucose
- Urinalysis
- Peak flow or spirometry
GPP – Transthoracic Doppler 2D echocardiographic examination should be performed to exclude important valve disease, assess the systolic (and diastolic) function of the (left) ventricle, and detect intracardiac shunts.
GPP – Transthoracic Doppler 2D echocardiographic studies should be performed on high-resolution equipment by experienced operators trained to the relevant professional standards. Need and demand for these studies should not compromise quality.
GPP – The reporting of Doppler 2D echocardiography should be by those experienced in doing so.
B – Alternative methods of imaging the heart should be considered when a poor image is produced by echocardiography. Such methods may include radionuclide angiography, cardiac magnetic resonance imaging, or transoesophageal Doppler 2D echocardiography.
Diastolic Heart Failure
GPP - Where the diagnosis is unclear, or if a diagnosis of diastolic heart failure is being considered, the patient should be referred for more specialist assessment.
Review of Existing Diagnoses
GPP- The basis for historical diagnoses of heart failure should be reviewed, and only patients whose diagnosis is confirmed should be managed in accordance with this guideline.
GPP - If the diagnosis of heart failure is still suspected, but confirmation of the underlying cardiac abnormality has not occurred, then the patient should have appropriate further investigation.
Treating Heart Failure
Treatments are available that can improve the life expectancy and quality of life of a person with heart failure. Treatment recommendations are given below and include aspects of lifestyle, pharmacological therapy, and invasive procedures. It is also helpful to consider the need to keep patients fully informed about their condition and the treatment options, and this is reflected in the recommendations.
Lifestyle
Exercise Training and Rehabilitation
B - Patients with heart failure should be encouraged to adopt regular aerobic and/or resistive exercise. This may be more effective when part of an exercise programme or a programme of rehabilitation.
Smoking
GPP - Patients must be strongly advised not to smoke. Referral to smoking cessation services should be considered.
Alcohol
C - Patients with alcohol-related heart failure should abstain from drinking alcohol.
GPP - Health care professionals should discuss alcohol consumption with the patient and tailor their advice appropriately to the clinical circumstances.
Sexual Activity
GPP - Health care professionals should be prepared to broach sensitive issues with patients, such as sexual activity, as these are unlikely to be raised by the patient.
Vaccination
GPP - Patients with heart failure should be offered an annual vaccination against influenza.
GPP - Patients with heart failure should be offered vaccination against pneumococcal disease (only required once).
Air Travel
GPP - Air travel will be possible for the majority of patients with heart failure, depending on their clinical condition at the time of travel.
Driving Regulations
GPP - Heavy Goods Vehicle and Public Service Vehicle license: physicians should be up to date with the latest Driver and Vehicle Licensing Authority guidelines. Check the Web site for regular updates: www.dvla.gov.uk/
Pharmacological Therapy for Patients with Heart Failure due to Left Ventricular (LV) Systolic Dysfunction
Drug therapy is required for the vast majority of patients with heart failure. It is the responsibility of the individual prescriber to check the dosage of medication. This document should be read as a guide to treatment rather than being considered a protocol that must be followed prescriptively in all patients. Treatment should be tailored to the individual patient, with referral for more specialist advice being considered where appropriate.
Note that at the time of issue of this guideline, the following drugs in this guideline are unlicensed in the United Kingdom for the treatment of heart failure or its common signs or symptoms.
- Angiotensin II receptor antagonists
- The positive inotropic agents (Dobutamine and Dopamine)
- Calcium channel blockers (Amiodipine)
Recommendations on Specific Drugs
Recommendations for pharmacological therapy for patients with heart failure due to left ventricular systolic dysfunction are summarised in the algorithm on page 22 in the full version of the original guideline document.
Diuretics
C - Diuretics should be routinely used for the relief of congestive symptoms and fluid retention in patients with heart failure and should be titrated (up and down) according to need following the initiation of subsequent heart failure therapies. Please refer to Table 4 in the full version of the original guideline document for information on specific dosages and side effects of diuretics.
Angiotensin-converting Enzyme (ACE) Inhibitors
A - All patients with heart failure due to left ventricular systolic dysfunction should be considered for treatment with an ACE inhibitor. Please refer to Table 5 in the full version of the original guideline document for information on practical recommendations on the use of ACE inhibitors.
A - ACE inhibitor therapy should be instituted in patients with heart failure due to left ventricular systolic dysfunction before beta-blockade is introduced.
GPP - ACE inhibitor therapy should be initiated at the appropriate dose and titrated upwards at short intervals (for example, every 2 weeks) until the optimal tolerated or target dose is achieved. (Refer to Table 5 in the full version of the original guideline document for information on practical recommendations on the use of ACE inhibitors.)
GPP – Blood biochemistry (urea, creatinine, and electrolytes) should be measured after initiation and at each dose increment.
Beta-blockers
A - Beta-blockers licensed for use in heart failure should be initiated in patients with heart failure due to left ventricular systolic dysfunction after diuretic and ACE inhibitor therapy (regardless of whether or not symptoms persist). (Refer to Table 6 in the full version of the original guideline for information on practical recommendations on the use of beta-blockers.)
C - Beta-blockade therapy for heart failure should be introduced in a "start low, go slow" manner, with assessment of heart rate, blood pressure, and clinical status after each titration.
GPP - Patients who develop heart failure due to left ventricular systolic dysfunction and who are already on treatment with a beta-blocker for a concomitant condition (for example, angina, hypertension) should continue with a beta-blocker – either their current beta-blocker or an alternative licensed for heart failure treatment.
Aldosterone Antagonists
A - Patients with heart failure due to left ventricular systolic dysfunction who remain moderately to severely symptomatic despite optimal therapy (as outlined in the algorithm in the original guideline document) should be prescribed spironolactone at a dose of 12.5 to 50 mg once per day, and specialist advice should be sought. (Refer to Table 7 in the full version of the original guideline document for specific information on practical recommendations for the use of spironolactone.)
GPP - Patients with heart failure taking spironolactone should have blood potassium and creatinine levels monitored for signs of hyperkalaemia and/or deteriorating renal function. If hyperkalaemia is a problem, then the dose of spironolactone should be halved and biochemistry rechecked.
Digoxin
Digoxin is recommended for:
- A
- Worsening or severe heart failure due to left ventricular systolic dysfunction despite ACE inhibitor, beta-blocker, and diuretic therapy
- C
- Patients with atrial fibrillation and any degree of heart failure
Angiotensin II Receptor Antagonists
A - At the time of issue of this guideline, angiotensin II receptor antagonists are not licensed in the United Kingdom for heart failure and studies are ongoing. However, angiotensin II receptor antagonists may provide an alternative to ACE inhibitors for patients intolerant of ACE inhibitors (for example, because of cough). (Refer to Table 8 of the full version in of the original guideline document for specific information on currently available angiotensin II receptor antagonists.)
GPP - The triple combination of ACE inhibitor, beta-blocker, and angiotensin II receptor antagonist should be avoided, pending the results of further trials.
Amiodarone
GPP - The decision to prescribe amiodarone should be made in consultation with a specialist.
GPP - The need to continue the prescription should be reviewed regularly.
GPP - Patients taking amiodarone should have a routine 6-monthly clinical review, including liver and thyroid function test, and including a review of side effects.
Anticoagulants
A - Anticoagulation is indicated for patients with the combination of heart failure and atrial fibrillation (also refer to the recommendations below concerning patients with heart failure and atrial fibrillation).
GPP - In patients with heart failure in sinus rhythm, anticoagulation should be considered for those with a history of thromboembolism, left ventricular aneurysm, or intracardiac thrombus.
Aspirin
B - Aspirin (75–150 mg once daily) should be prescribed for patients with the combination of heart failure and atherosclerotic arterial disease (including coronary heart disease).
Statins (Hydroxymethylglutaryl-coenzyme A Reductase Inhibitors)
GPP - Patients with the combination of heart failure and known atherosclerotic vascular disease should receive statins only in accordance with current indications. Specific trials in this area are ongoing.
Isosorbide/hydralazine Combination (Specialist Initiation Only)
A - An isosorbide/hydralazine combination may be used in patients with heart failure who are intolerant of ACE inhibitors or angiotensin II receptor antagonists.
Inotropic Agents (specialist use only)
A - Intravenous inotropic agents (such as dobutamine, milrinone, or enoximone) should only be considered for the short-term treatment of acute decompensation of chronic heart failure. This will require specialist advice.
Calcium Channel Blockers
A - Amlodipine should be considered for the treatment of comorbid hypertension and/or angina in patients with heart failure, but verapamil, diltiazem, or short-acting dihydropyridine agents should be avoided.
Major Comorbidities that Impact on the Pharmacological Management of Heart Failure
The presence of certain comorbidities may affect the drugs that can be used for the treatment of heart failure or increase the likelihood of side effects. The major comorbidities that impact on the management of heart failure are summarised in Table 9 in the full version of the original guideline document.
Side Effects of Drugs Commonly Used in the Treatment of Heart Failure
All drugs have side effects. See the Summary of Product Characteristics for individual drugs for details.
Improving Adherence to Pharmacological Therapy
B - Dosing regimens should be kept as simple as possible, and the health care professional should ensure that the patient and carer are fully informed about their medication.
Invasive Procedures
Although drug therapy is the mainstay of treatment of heart failure, some patients will also benefit from diagnostic or interventional invasive procedures. These procedures are normally organised by a specialist. This guideline can only give general advice, and specialist advice is strongly recommended where such procedures might be considered.
Coronary Revascularisation
C - Coronary revascularisation should not be routinely considered in patients with heart failure due to systolic left ventricular impairment, unless they have refractory angina.
Cardiac Transplantation
C
- Specialist referral for transplantation should be considered in patients with severe refractory symptoms or refractory cardiogenic shock.
Cardiac Resynchronisation Therapy
A - Resynchronisation therapy should be considered in selected patients with left ventricular systolic dysfunction (left ventricular ejection fraction <35%), drug refractory symptoms, and a QRS duration >120 ms. The results of ongoing trials will help guide appropriate patient selection.
Implantable Cardioverter-Defibrillators (ICDs)
NICE 2000 – Recommendation from NICE Technology Appraisal Guidance No. 11, "Guidance on the use of implantable cardioverter defibrillators for arrhythmias" (Available from: www.nice.org.uk/Docref.asp?d=10239).
The use of ICDs should be routinely considered for patients in the following categories:
- Secondary prevention, that is for patients who present, in the absence of a treatable cause, with:
- Cardiac arrest due to either ventricular tachycardia (VT) or ventricular fibrillation
- Spontaneous sustained VT causing syncope or significant haemodynamic compromise
- Sustained VT without syncope/cardiac arrest, and who have an associated reduction in ejection fraction (less than 35%) but are no worse than Class III* of the New York Heart Association functional classification of heart failure
- "Primary prevention" for patients with:
- A history of previous myocardial infarction and all of the following:
- Non-sustained VT on Holter (24-hour ECG) monitoring
- inducible VT on electrophysiological testing
- Left ventricular dysfunction with an ejection fraction less than 35% and no worse than Class III* of the New York Heart Association functional classification of heart failure
- A familial cardiac condition with a high risk of sudden death, including long QT syndrome, hypertrophic cardiomyopathy, Brugada syndrome, arrhythmogenic right ventricular dysplasia, and following repair of tetralogy of Fallot.
*Note: Marked limitation of physical activity. Although patients are comfortable at rest, less than ordinary physical activity will lead to symptoms (symptomatically "moderate" heart failure)
Oxygen Therapy and Continuous Airway Pressure
The evidence for oxygen therapy and continuous positive airway pressure was considered during development of this guideline, but it was not possible to make specific recommendations because of the small evidence base. For further details, see the full version of the original guideline document.
Recommendations for Treatment of Heart Failure Not Due to Left Ventricular Systolic Dysfunction
Valve Disease
C - Patients with heart failure due to valve disease should be referred for specialist assessment and advice regarding follow-up.
C - ACE inhibitor therapy should not be initiated in a patient with a clinical suspicion of haemodynamically significant valve disease, until the valve disease has been assessed by a specialist.
Patients with valve disease (but no heart failure) should also be assessed by a specialist, as the onset of heart failure increases the risk of surgery and reduces the likelihood of full recovery.
Diastolic Dysfunction
GPP - The diagnosis and treatment of diastolic dysfunction should be made by a specialist, and other conditions that present in a similar way may need to be considered. Patients in whom this diagnosis has been made should usually be treated with a low to medium dose of loop diuretics (for example, less than 80 mg furosemide per day). Patients who do not respond to this treatment will require further specialist advice.
Other Causes
The management of other causes of heart failure requires specialist input. This would include congenital heart disease, cardiomyopathies, and specific heart muscle disease such as amyloid.
Recommendations for Patients with Heart Failure and Atrial Fibrillation
C - For patients with heart failure and atrial fibrillation, specialist advice should be sought as to whether the aim is improvement of heart rate control or cardioversion (return to sinus rhythm).
A - Anticoagulation is indicated for patients with heart failure and atrial fibrillation (see also recommendations above concerning anticoagulation).
Recommendations for Different Subgroups of Patients with Heart Failure
Age
A - The management of heart failure should be determined by clinical criteria, irrespective of the age of the patient.
GPP - Tolerance of drugs may be lower and side effects require closer and more frequent monitoring in older patients.
Gender
GPP - The principles of pharmacological management of heart failure should be the same for men and women.
GPP - The potential teratogenic effects of drugs should be considered.
Pregnancy
GPP - In women of reproductive age who have heart failure, contraception and pregnancy should be discussed. If pregnancy is being considered or occurs, specialist advice should be sought. Subsequently, specialist care should be shared between the cardiologist and obstetrician.
Ethnicity
GPP - The principles of pharmacological management should be the same for all patients with heart failure, regardless of ethnicity.
Monitoring
The clinical condition of a person with heart failure may fluctuate, and repeated admission to hospital is common, particularly for patients with more severe heart failure. Monitoring of clinical status is necessary and will involve health care professionals in both primary and secondary care. Patients and their carers are playing an increasing role in monitoring, but this requires appropriate education and support.
Clinical Review
GPP - All patients with chronic heart failure require monitoring. This monitoring should include (Refer to the information below and to section 8.1 in the full version of the original guideline document for specific information on assessments to be made at clinical review):
- A clinical assessment of functional capacity, fluid status, cardiac rhythm (minimum of examining the pulse), cognitive status, and nutritional status
- A review of medication, including need for changes and possible side effects
- Serum urea, electrolytes, and creatinine*
*Note: This is a minimum. Patients with comorbidities or coprescribed medications will require further monitoring. Monitoring serum potassium is particularly important if a patient is taking digoxin or spironolactone.
Assessments to be Made at Clinical Review
Assessment of Functional Capacity
Chiefly from history, but more objectively by use of New York Heart Association class, specific quality-of-life questionnaires, 6-minute walk test, or maximal exercise test. Note: Not all of these tests are likely to be necessary or appropriate at each assessment.
Assessment of Fluid Status
Chiefly by physical examination – changes in body weight, extent of jugular venous distension, lung crackles and hepatomegaly, extent of peripheral oedema, and lying and standing blood pressure (postural drop in blood pressure may indicate hypovolaemia)
Assessment of Cardiac Rhythm
Chiefly by clinical examination, but may require 12-lead electrocardiogram (ECG) or 24-hour electrocardiographic ("Holter") monitoring if suspicion of arrhythmia
Laboratory Assessment
Checking of serum biochemistry (urea, electrolytes, creatinine) is essential, but other tests (such as thyroid function, haematology, liver function, level of anticoagulation) may also be required depending on the medication prescribed and comorbidity.
GPP – More detailed monitoring will be required if the patient has significant comorbidity or their condition has deteriorated since the previous review.
GPP – The frequency of monitoring should depend on the clinical status and stability of the patient. The monitoring interval should be short (days to 2 weeks) if the clinical condition or medication has changed but is required at least 6 monthly for stable patients with proven heart failure.
GPP- Patients who wish to be involved in monitoring of their condition should be provided with sufficient education and support from their health care professional to do this, with clear guidelines as to what to do in the event of deterioration.
Therapeutic Drug Monitoring of Serum Digoxin Concentrations
GPP – Routine monitoring of serum digoxin concentrations is not recommended. A digoxin concentration measured within 8 to 12 hours of the last dose may be useful to confirm a clinical impression of toxicity or non-compliance.
GPP – The serum digoxin concentration should be interpreted in the clinical context, as toxicity may occur even when the concentration is within the "therapeutic range."
Referral and Approach to Care
The management of heart failure is likely to be shared between health care professionals in both primary and secondary care. Patients and their carers are increasingly involved in management decisions. Work with patient focus groups suggests that the major failings of management relate to poor communication between health care professionals, and between health care professionals and the patients they care for.
Referral for More Specialist Advice
GPP - Patients with heart failure require specialist advice in the following situations:
- Heart failure due to valve disease, diastolic dysfunction or any other cause except left ventricular systolic dysfunction
- One or more of the comorbidities outlined in Table 9 in the full version of the original guideline document
- Angina, atrial fibrillation, or other symptomatic arrhythmia
- Women who are planning a pregnancy or who are pregnant
GPP - The following situations also require referral:
- Severe heart failure
- Heart failure that does not respond to treatment as discussed in this guideline and outlined in the algorithm on page 54 in the full version of the original guideline document
- Heart failure that can no longer be managed effectively in the home setting
Discharge Planning
GPP - Patients with heart failure should generally be discharged from hospital only when their clinical condition is stable and the management plan is optimised. Timing of discharge should take into account patient and carer wishes and the level of care and support that can be provided in the community.
GPP - The primary care team, patient and carer must be aware of the management plan.
GPP - Clear instructions should be given as to how the patient/carer can access advice, particularly in the high-risk period immediately following discharge.
Multidisciplinary Team Approach to Heart Failure Management
A - Heart failure care should be delivered by a multidisciplinary team with an integrated approach across the health care community.
Non-National Health Service (NHS) Agencies
GPP - Standard one of The Older People National Service Framework (NSF) states: Social care services will not use age in their eligibility criteria or policies to restrict access to available services. This applies to patients with heart failure. (See www.doh.gov.uk/nsf/olderpeople.htm)
GPP - Management plans for patients with heart failure should be discussed with non-NHS agencies where they are involved in or responsible for the care of a person with heart failure.
GPP - The principles of pharmacological management for a patient cared for in a non-NHS institution should be similar to those for any other patient with heart failure.
GPP - The education needs of non-NHS agency carers should be considered.
Supporting Patients and Carers
Understanding the information needs of patients and carers is vital. Key issues identified by patient focus groups include the importance of honesty and accurate information, and the potential value of support groups. The recommendations below are based on earlier consensus guidelines produced by a Royal College of Physicians’ working party.
Communication
GPP - Good communication between health care professionals and patients and carers is essential for the best management of heart failure.
C - Guidelines for good communication.
- Listen to patients and respect their views and beliefs.
- Give patients the information they ask for or need about their condition, its treatment, and prognosis, in a way they can understand, including information about any serious side effects of drugs to be prescribed.
- Provide the most important information first.
- Explain how each item will affect patients personally.
- Present information in separate categories.
- Make advice specific, detailed, and concrete.
- Use words the patients will understand; confirm understanding by questions; define unfamiliar words; write down key words; draw diagrams, and keep a copy in the medical notes.
- Repeat the information using the same words each time.
- Prepare material, written or taped, to back up handwritten notes.
- Share information with patients' partners, close relatives, or carers if they ask you to do so. When patients cannot indicate their consent for such sharing of information, it is advisable to share the information that those close to the patient need or want to know, except where you have reason to believe that the patient would object if able to do so.
C - The content, style and timing of information provision should be tailored to the needs of the individual patient.
GPP - Health care professionals should assess cognitive ability when sharing information.
GPP - Carers and relatives of patients who are cognitively impaired should be made aware of treatment regimens for the patients they care for and be encouraged to identify any need for clinical support.
GPP - Management of heart failure should be seen as a shared responsibility between patient and health care professional.
GPP - Unless specifically excluded by the patient, carers and relatives should be involved in the management of the patient, particularly where the patient cannot look after him- or herself.
Prognosis
GPP – Prognosis should be discussed with patients and carers in a sensitive, open, and honest manner.
Support Groups
GPP – Health care professionals should be aware of local cardiac support networks and provide this information to patients and carers.
Anxiety and Depression
Depression tends to be more common in patients with heart failure than in the general population. Drug therapy with antidepressants may lead to complications such as fluid retention, hypotension, and arrhythmias.
C - The diagnosis of depression should be considered in all patients with heart failure.
C - Where depression is likely to have been precipitated by heart failure symptoms, then reassessment of psychological status should be undertaken once the physical condition has stabilised following treatment for heart failure. If the symptoms have improved, no further specific treatment for depression is required.
C - Where it is apparent that depression is co-existing with heart failure, then the patient should be treated for depression following the NICE guideline ("Depression: the management of depression in primary and secondary care"), scheduled for publication in February 2004.
GPP - For patients with heart failure, the potential risks and benefits of drug therapies for depression should be considered carefully.
GPP - Patients with heart failure should consult a health care professional before using over-the-counter therapies for depression such as St John’s wort (Hypericum perforatum). Health care professionals should be aware of the potential interaction with prescribed medication and should always ask about self-medication, including the use of herbal products.
End of Life Issues
There is substantial evidence for considerable unmet palliative needs of patients with heart failure and their informal carers. The main areas of need include symptom control, psychological and social support, planning for the future, and end of life care.
GPP - Issues of sudden death and living with uncertainty are pertinent to all patients with heart failure. The opportunity to discuss these issues should be available at all stages of care.
GPP - The palliative needs of patients and carers should be identified, assessed, and managed at the earliest opportunity.
GPP - Patients with heart failure and their carers should have access to professionals with palliative care skills within the heart failure team.
Definitions:
Evidence Categories
Ia: Evidence obtained from systematic review of meta-analysis of randomised controlled trials
Ib: Evidence obtained from at least one randomised controlled trial
IIa: Evidence obtained from at least one well-designed controlled study without randomisation
IIb: Evidence obtained from at least one other type of well-designed quasi-experimental study
III: Evidence obtained from well-designed non-experimental descriptive studies, such as comparative studies, correlation studies and case studies
IV: Evidence obtained from expert committee reports or opinions and/or clinical experience of respected authorities.
Grading of Recommendations
A: At least one randomised controlled trial as part of a body of literature of overall good quality and consistency addressing the specific recommendation (evidence levels Ia and Ib)
B: Well-conducted clinical studies but no randomised clinical trials on the topic of recommendation (evidence levels IIa, IIb, and III)
C: Expert committee reports or opinions and/or clinical experience of respected authorities. This grading indicates that directly applicable clinical studies or good quality are absent (evidence level IV).
GPP: Recommended good practice based on the clinical experience of the Guideline Development Group
DS: Diagnostic studies
NICE: Evidence from the National Institute for Clinical Excellence (NICE) guidelines or health technology appraisal programme