ISBN: 978-1-4731-3093-7 9.5.2 Transition between heart failure care settings 419 9.5.3 Information and support needs regarding diagnosis and prognosis 420 10 Advanced heart failure and palliative care 421 10.1 Diuretics in advanced heart failure 421 10.1.2 Review question: Which route of administration of diuretics (intravenous (IV), subcutaneous or oral) is most clinically and cost effective in people with advanced heart failure who are in the community, including patients receiving palliative care? 421 10.1.6 Recommendations and link to evidence 422 10.2 Domiciliary oxygen therapy in people with advanced heart failure 424 10.2.2 Review question: What is the effectiveness of domiciliary oxygen therapy in people with advanced heart failure 424 10.2.6 Recommendations and link to evidence 428 10.3 Discussing Implantable Cardioverter Defibrillatior (ICD) deactivation 430 10.3.2 Review question: What criteria should determine when to discuss defibrillator deactivation? 430 10.3.6 Recommendations and link to evidence 446 10.4 Identifying patients with an increased risk of mortality 450 10.4.2 Review question: In adults with heart failure, which validated risk tools best identify patients with heart failure who are at increased risk of mortality in the short term (up to 1 year)? 450 10.4.4 Discrimination and calibration 466 10.4.7 Recommendations and link to evidence 472 Chronic Heart Failure Contents NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 11 Reference list 478 12 Acronyms and abbreviations 507 13.1 Guideline-specific terms 512 13.2 General terms 513 Chronic Heart Failure Acknowledgements NICE 2018. All rights reserved. Subject to Notice of rights.


ISBN: 978-1-4731-3093-7 11 Reference list 478 12 Acronyms and abbreviations 507 13.1 Guideline-specific terms 512 13.2 General terms 513 Chronic Heart Failure Acknowledgements NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Guideline committee members Name Role Rajai Ahmad Consultant Cardiologist, Sandwell an d West Birmingham Hospitals NHS Trust Abdallah Al-Mohammad Consultant Cardiologist, Northern General Hospital Martin Cowie Honorary Consultant, Cardiologist, Royal Brompton & Harefield NHS Trust (resigned Dec 2016) Suzannah Hardman Consultant Cardiologist with an interest in Community Cardiology, Whittington Health Nick Hartshorn-Evans Lay Member Rani Khatib Consultant Pharmacist Cardiology and Cardiovascular Clinical Research, Leeds Teaching Hospitals, NHS Trust Richard Mindham Lay Member Jim Moore General Practitioner, Gloucestershire Rebekah Schiff Consultant Geriatrician and General Physician, Guy s & St Thomas NHS Trust Sue Simpson Head of Cardiac Care, Oxleas NHS Trust Clare Taylor General Practitioner, University of Birmingham Anthony Wierzbicki (Chair) Consultant in Metabolic Medicine and Chemical Pathology, Guys & St Thomas NHS Trust NGC technical team members Name Role Kate Ashmore Document Editor/Process Assistant (until Feb 2018) Resham Baruah Specialist Trainee in Cardiology (from Oct 2017) Rebecca Boffa Research Fellow Emma Brockis Senior Health Economist Jill Cobb Information Specialist Katrina Davis Research Fellow (Dec 2016 Jul 2017) Dalia Dawoud Senior Health Economist (until Sep 2016) Francesca Faesin Research Fellow (until Oct 2016) Elisabetta Fenu Senior Health Economist (Sep 2016 Dec 2016) Sophia Kemmis-Betty Senior Health Economist (from Dec 2016) Amy Kelsey Senior Project Manager (from Oct 2017) Liz Pearton Information Specialist Ben Pordes Senior Project Manager (until Oct 2017) Emma Pottinger Senior Research Fellow (Sep 2017-Feb 2018) Silvia Rabar Senior Research Fellow (from Feb 2018) Jacqui Real Senior Research Fellow (until Oct 2017) Gill Ritchie Guideline Lead Joseph Runicles Information Specialist Grit Scheffler-Ansari Research Fellow (Sep Nov 2017) Chronic Heart Failure Acknowledgements NICE 2018.


ISBN: 978-1-4731-3093-7 Guideline committee members Name Role Rajai Ahmad Consultant Cardiologist, Sandwell an d West Birmingham Hospitals NHS Trust Abdallah Al-Mohammad Consultant Cardiologist, Northern General Hospital Martin Cowie Honorary Consultant, Cardiologist, Royal Brompton & Harefield NHS Trust (resigned Dec 2016) Suzannah Hardman Consultant Cardiologist with an interest in Community Cardiology, Whittington Health Nick Hartshorn-Evans Lay Member Rani Khatib Consultant Pharmacist Cardiology and Cardiovascular Clinical Research, Leeds Teaching Hospitals, NHS Trust Richard Mindham Lay Member Jim Moore General Practitioner, Gloucestershire Rebekah Schiff Consultant Geriatrician and General Physician, Guy s & St Thomas NHS Trust Sue Simpson Head of Cardiac Care, Oxleas NHS Trust Clare Taylor General Practitioner, University of Birmingham Anthony Wierzbicki (Chair) Consultant in Metabolic Medicine and Chemical Pathology, Guys & St Thomas NHS Trust NGC technical team members Name Role Kate Ashmore Document Editor/Process Assistant (until Feb 2018) Resham Baruah Specialist Trainee in Cardiology (from Oct 2017) Rebecca Boffa Research Fellow Emma Brockis Senior Health Economist Jill Cobb Information Specialist Katrina Davis Research Fellow (Dec 2016 Jul 2017) Dalia Dawoud Senior Health Economist (until Sep 2016) Francesca Faesin Research Fellow (until Oct 2016) Elisabetta Fenu Senior Health Economist (Sep 2016 Dec 2016) Sophia Kemmis-Betty Senior Health Economist (from Dec 2016) Amy Kelsey Senior Project Manager (from Oct 2017) Liz Pearton Information Specialist Ben Pordes Senior Project Manager (until Oct 2017) Emma Pottinger Senior Research Fellow (Sep 2017-Feb 2018) Silvia Rabar Senior Research Fellow (from Feb 2018) Jacqui Real Senior Research Fellow (until Oct 2017) Gill Ritchie Guideline Lead Joseph Runicles Information Specialist Grit Scheffler-Ansari Research Fellow (Sep Nov 2017) Chronic Heart Failure Acknowledgements NICE 2018. All rights reserved. Subject to Notice of rights.


All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Co-optees Name Role Darren Green Consultant Nephrologist and Acute Physician, Salford Royal Foundation Trust Hasnain Dalal Senior Clinical Researcher, Royal Cornwall Hospitals; Honorary Clinical Associate Professor, University of Exeter Medical School Suzanne Kite Palliative Care Physician Kath Measures Clinical Specialist Physiotherapist in Cardiology Simon Corbett Consultant Cardiologist, University Hospital Southampton Rod Taylor Professor in Health Services Research (Medical Statistics & Clinical Trials), Director of Exeter Clinical Trials Unit Peer reviewers Name Role Martin Cowie Honorary Consultant, Cardiologist, Royal Brompton & Harefield NHS Trust Chronic Heart Failure Acknowledgements NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Acknowledgements The development of this guideline was greatly assisted by the following people: Professor Martin Cowie for reviewing the economic model methodology section prior to running the sensitivity analyses. Chronic Heart Failure Guideline summary NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 1 Guideline summary 1.1 Full list of recommendations 1. Take a careful and detailed history, and perform a clinical examination and tests to confirm the presence of heart failure. [2010] 2. Measure N-terminal pro-B-type natriuretic peptide [NT-proBNP] in people with suspected heart failure. [2018] 3. Because very high levels of NT-proBNP carry a poor prognosis, refer people with suspected heart failure and an NT-proBNP level above 2,000 ng/litre (236 pmol/litre) urgently, to have specialist assessment and transthoracic echocardiography within 2 weeks. [ 2018] 4. Refer people with suspected heart failure and an NT-proBNP level between 400 and 2,000 ng/litre (47 to 236 pmol/litre) to have specialist assessment and transthoracic echocardiography within 6 weeks. [2018] 5.


Refer people with suspected heart failure and an NT-proBNP level between 400 and 2,000 ng/litre (47 to 236 pmol/litre) to have specialist assessment and transthoracic echocardiography within 6 weeks. [2018] 5. Be aware that: an NT-proBNP level less than 400 ng/litre (47 pmol/litre) in an untreated person makes a diagnosis of heart failure less likely the level of serum natriuretic peptide does not differentiate between heart failure with reduced ejection fraction and heart failure with preserved ejection fraction. [2018] 6. Review alternative causes for symptoms of heart failure in people with NT- proBNP levels below 400 ng/litre. If there is still concern that the symptoms might be related to heart failure, discuss with a physician with subspeciality training in heart failure. [2018] 7. Be aware that: obesity, African or African-Caribbean family origin, or treatment with diuretics, angiotensin-converting enzyme(ACE) inhibitors , beta- blockers, angiotensin II receptor blockers (ARBs) or mineralcorticoid receptor antagonist (MRAs) can reduce levels of serum natriuretic peptides. high levels of serum natriuretic peptides can have causes other than heart failure (for example, age over 70 years, left ventricular hypertrophy, ischaemia, tachycardia, right ventricular overload, hypoxaemia [including pulmonary embolism], renal dysfunction ], sepsis, chronic obstructive pulmonary disease, diabetes, or cirrhosis of the liver). [2010, 8. Perform transthoracic echocardiography to exclude important valve disease, assess the systolic (and diastolic) function of the (left) ventricle, and detect intracardiac shunts. [2003, amended 2018] 9. Transthoracic echocardiography should be performed on high-resolution equipment, by experienced operators trained to the relevant professional Chronic Heart Failure Guideline summary NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 standards. Need and demand for these studies should not compromise 10. Ensure that those reporting echocardiography are experienced in doing so. 11.


Ensure that those reporting echocardiography are experienced in doing so. 11. Consider alternative methods of imaging the heart (for example, radionuclide angiography [multigated acquisition scanning], cardiac MRI or transoesophageal echocardiography) if a poor image is produced by transthoracic echocardiography. [2003, amended 2018] 12. Perform an ECG and consider the following tests to evaluate possible aggravating factors and/or alternative diagnoses: chest X-ray blood tests: renal function profile thyroid function profile liver function profile lipid profile glycosylated haemoglobin (HbA1c) full blood count urinalysis peak flow or spirometry. [2010, amended 2018] 13. Try to exclude other disorders that may present in a similar manner.[2003] 14. When a diagnosis of heart failure has been made, assess severity, aetiology, precipitating factors, type of cardiac dysfunction and correctable causes. 15. Refer people with heart failure caused by valve disease for specialist assessment and advice regarding follow-up. [2003] 16. Review the basis for a historical diagnosis of heart failure, and manage care in accordance with this guideline only if the diagnosis is confirmed. [2003] 17. If the diagnosis of heart failure is still suspected, but confirmation of the underlying cardiac abnormality has not occurred, then the person should have appropriate further investigation. [2003] 18. Do not routinely advise people with heart failure to restrict their sodium or fluid consumption. Ask about salt and fluid consumption and, if needed, advise as follows: restricting fluids for people with dilutional hyponatraemia reducing intake for people with high levels of salt and/or fluid consumption. Continue to review the need to restrict salt or fluid. 19. Advise people with heart failure to avoid salt substitutes that contain 20. Offer people with heart failure an annual vaccination against influenza. Chronic Heart Failure Guideline summary NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 21.


All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 21. Offer people with heart failure vaccination against pneumococcal disease (only required once). [2003] 22. In women of childbearing potential 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. ]2003] 23. Air travel will be possible for the majority of people with heart failure, depending on their clinical condition at the time of travel. [2003] 24. Large Goods Vehicle and Passenger Carrying Vehicle licence: physicians should be up to date with the latest Driver and Vehicle Licensing Agency guidelines. Check the website for regular updates [2003] 25. Diuretics should be routinely used for the relief of congestive symptoms and fluid retention in people with heart failure, and titrated (up and down) according to need following the initiation of subsequent heart failure 26. People who have heart failure with preserved ejection fraction should usually be offered a low to medium dose of loop diuretics (for example, less than 80 mg furosemide per day). People whose heart failure does not respond to this treatment will need further specialist advice. [2003, amended 2018] 27. Avoid verapamil, diltiazem and short-acting dihydropyridine agents in people who have heart failure with reduced ejection fraction. [2003, amended 2018] 28. Make the decision to prescribe amiodarone in consultation with a specialist. 29. Review the need to continue the amiodarone prescription at the 6-monthly clinical review. [2003, amended 2018] 30. Offer people taking amiodarone liver and thyroid function tests, and a review of side effects, as part of their routine 6-monthly clinical review. [2003, 31.


Offer people taking amiodarone liver and thyroid function tests, and a review of side effects, as part of their routine 6-monthly clinical review. [2003, 31. For people who have heart failure and atrial fibrillation, follow the recommendations on anticoagulation in the NICE guideline on atrial fibrillation. Be aware of the effects of impaired renal and liver function on anticoagulant therapies. [2018] 32. In people with heart failure in sinus rhythm, anticoagulation should be considered for those with a history of thromboembolism, left ventricular aneurysm or intracardiac thrombus. [2003] 33. Offer an angiotensin-converting enzyme (ACE) inhibitor and a beta-blocker licensed for heart failure to people who have heart failure with reduced ejection fraction. Use clinical judgement when deciding which drug to start first. [2010 ] 34. Do not offer ACE inhibitor therapy if there is a clinical suspicion of haemodynamically significant valve disease until the valve disease has been assessed by a specialist. [2003] 35. Do not withhold treatment with a beta-blocker solely because of age or the presence of peripheral vascular disease, erectile dysfunction, diabetes, interstitial pulmonary disease or chronic obstructive pulmonary disease. Chronic Heart Failure Guideline summary NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 36. Start ACE inhibitor therapy at a low dose and titrate upwards at short intervals (for example, every 2 weeks) until the target or maximum tolerated dose is reached. [2010] 37. Measure serum sodium and potassium and assess renal function before and 1 to 2 weeks after starting an ACE inhibitor, and after each dose 38. Measure blood pressure before and after each dose increment of an ACE inhibitor. Follow the recommendations on measuring blood pressure, including measurement in people with symptoms of postural hypotension, in the NICE guideline on hypertension in adults. [2018] 39.


Follow the recommendations on measuring blood pressure, including measurement in people with symptoms of postural hypotension, in the NICE guideline on hypertension in adults. [2018] 39. Once the target or maximum tolerated dose of an ACE inhibitor is reached, monitor treatment monthly for 3 months and then at least every 6 months, and at any time the person becomes acutely unwell. [2010, amended 2018] 40. Introduce beta-blockers in a start low, go slow manner. Assess heart rate, and clinical status after each titration. Measure blood pressure before and after each dose increment of a beta-blocker. [2010, amended 2018] 41. Switch people whose condition is stable and who are already taking a beta- blocker for a comorbidity (for example, angina or hypertension), and who develop heart failure with reduced ejection fraction, to a beta-blocker licensed for heart failure. [2010] 42. Consider an angiotensin II receptor blocker (ARB) licensed for heart failure as an alternative to an ACE inhibitor for people who have heart failure with reduced ejection fraction and intolerable side effects with ACE inhibitors. 43. Measure serum sodium and potassium and assess renal function before and after starting an ARB and after each dose increment.[2010, amended 2018] 44. Measure blood pressure after each dose increment of an ARB. Follow the recommendations on measuring blood pressure, including measurement in people with symptoms of postural hypotension, in the NICE guideline on hypertension in adults. [2018] 45. Once the target or maximum tolerated dose of an ARB is reached, monitor treatment monthly for 3 months and then at least every 6 months, and at any time the person becomes acutely unwell. [2010 amended 2018] 46.


Once the target or maximum tolerated dose of an ARB is reached, monitor treatment monthly for 3 months and then at least every 6 months, and at any time the person becomes acutely unwell. [2010 amended 2018] 46. If neither ACE inhibitors nor ARBs are tolerated, seek specialist advice and consider hydralazine in combination with nitrate for people who have heart failure with reduced ejection fraction. [2010] 47. Offer a mineralcorticoid receptor antagonist (MRA) in addition to an angiotensin-converting enzyme inhibitor (ACE) or ARB and beta-blocker, to people who have heart failure with reduced ejection fraction if they continue to have symptoms of heart failure. [2018] 48. Measure serum sodium and potassium and assess renal function before and after starting an MRA and after each dose increment. [2018] 49. Measure blood pressure before and after each dose increment of MRA. Follow the recommendations on measuring blood pressure, including measurement in people with symptoms of postural hypotension, in the NICE guideline on hypertension in adults. [2018] Chronic Heart Failure Guideline summary NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 50. Once the target, or maximum tolerated, dose of an MRA is reached, monitor treatment monthly for 3 months and then at least every 6 months, and at any time the person becomes acutely unwell. [2018] 51. Ivabradine is recommended as an option for treating chronic heart failure for people: with New York Heart Association (NYHA) class II to IV stable chronic heart failure with systolic dysfunction and who are in sinus rhythm with a heart rate of 75 beats per minute (bpm) or more and who are given ivabradine in combination with standard therapy including beta-blocker therapy, angiotensin-converting enzyme (ACE) inhibitor and aldosterone antagonists, or when beta-blocker therapy is contraindicated or not tolerated and 52.


Ivabradine is recommended as an option for treating chronic heart failure for people: with New York Heart Association (NYHA) class II to IV stable chronic heart failure with systolic dysfunction and who are in sinus rhythm with a heart rate of 75 beats per minute (bpm) or more and who are given ivabradine in combination with standard therapy including beta-blocker therapy, angiotensin-converting enzyme (ACE) inhibitor and aldosterone antagonists, or when beta-blocker therapy is contraindicated or not tolerated and 52. Ivabradine should only be initiated after a stabilisation period of 4 weeks on optimised standard therapy with ACE inhibitors, beta-blockers and aldosterone antagonists. [2012] 53. Ivabradine should be initiated by a heart failure specialist with access to a multidisciplinary heart failure team. Dose titration and monitoring should be carried out by a heart failure specialist, or in primary care by either a GP with a special interest in heart failure or a heart failure specialist nurse. [2012] 54. Sacubitril valsartan is recommended as an option for treating symptomatic chronic heart failure with reduced ejection fraction, only in people With New York Heart Association (NYHA) class II to IV symptoms and With a left ventricular ejection fraction of 35% or less and Who are already taking a stable dose of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor-blockers (ARBS) [2016] 55. Treatment with sacubitril valsartan should be started by a heart failure specialist with access to a multidisciplinary heart failure team. Dose titration and monitoring should be performed by the most appropriate team members as defined in NICE s guideline on chronic heart failure in adults: diagnosis and management. [2016] 56. This guidance is not intended to affect the position of patients whose treatment with sacubitril valsartan was started within the NHS before this guidance was published.


This guidance is not intended to affect the position of patients whose treatment with sacubitril valsartan was started within the NHS before this guidance was published. Treatment of those patients may continue without change to whatever funding arrangements were in place for them before this guidance was published until they and their NHS clinician consider it appropriate to stop. [2016] Hydralazine in combination with nitrate 57. Seek specialist advice and consider offering hydralazine in combination with nitrate (especially if the person is of African or Caribbean family origin and has moderate to severe heart failure [NYHA class III/IV] with reduced ejection Digoxin For recommendations on digoxin for people with atrial fibrillation see the section on rate and rhythm control in the NICE guideline on atrial fibrillation Chronic Heart Failure Guideline summary NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 58. Digoxin is recommended for worsening or severe heart failure with reduced ejection fraction despite first line treatment for heart failure. Seek specialist advice before initiating.[2010, amended 2018] 59. Routine monitoring of serum digoxin concentrations is not recommended. A digoxin concentration measured within 8 12 hours of the last dose may be useful to confirm a clinical impression of toxicity or non-adherence[2003] 60. the serum digoxin concentration should be interpreted in the clinical context as toxicity may occur even when the concentration is within the therapeutic 61. For people who have heart failure with reduced ejection fraction and chronic kidney disease with an eGFR of 30 ml/min/1,73 m2 or above: (estimated glomerular filtration rate) as follows. Offer the treatment outlined in section 6.2.7 and If the person s eGFR is 45 ml/min/1.73 m2 or below, consider lower doses and/or slower titration of dose of ACE inhibitors or ARBs, mineralcorticoid receptor antagonists and digoxin. [2018] 62.


Offer the treatment outlined in section 6.2.7 and If the person s eGFR is 45 ml/min/1.73 m2 or below, consider lower doses and/or slower titration of dose of ACE inhibitors or ARBs, mineralcorticoid receptor antagonists and digoxin. [2018] 62. For people who have heart failure with reduced ejection fraction and chronic kidney disease with an eGFR below 30 ml/min/1.73 m2 the specialist heart failure MDT should consider liaising with a renal physician [2018] 63. Monitor the response to titration of medicines closely in people who have heart failure with reduced ejection fraction and chronic kidney disease, taking into account the increased risk of hyperkalaemia. [2018] 64. Do not routinely offer coronary revascularisation to people who have heart failure with reduced ejection fraction and coronary artery disease. [2018] 65. Specialist referral for transplantation should be considered for people with severe refractory symptoms or refractory cardiogenic shock [2003] 66. Offer people with heart failure a personalised, exercise-based cardiac rehabilitation programme, unless their condition is unstable. The programme: should be preceded by an assessment to ensure that it is suitable for the person should be provided in a format and setting (at home, in the community or in the hospital) that is easily accessible for the person should include a psychological and educational component may be incorporated within an existing cardiac rehabilitation programme should be accompanied by information about support available from healthcare professionals when the person is doing the programme. 67. All people with chronic heart failure need monitoring. This monitoring should include: 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 Chronic Heart Failure Guideline summary NICE 2018. All rights reserved. Subject to Notice of rights.


This monitoring should include: 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 Chronic Heart Failure Guideline summary NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 an assessment of renal function. [2010, amended 2018] 68. More detailed monitoring will be needed if the person has significant comorbidity or if their condition has deteriorated since the previous review. 69. The frequency of monitoring should depend on the clinical status and stability of the person. The monitoring interval should be short (days to 2 weeks) if the clinical condition or medication has changed, but is needed at least 6-monthly for stable people with proven heart failure. [2003] 70. People with heart failure who wish to be involved in monitoring of their condition should be provided with sufficient education and support from their healthcare professional to do this, with clear guidelines as to what to do in the event of deterioration. [2003] 71. Consider measuring NT-proBNP (N-terminal pro-B-type natriuretic peptide) as part of a treatment optimisation protocol only in a specialist care setting for people aged under 75 who have heart failure with reduced ejection fraction and an eGFR above 60 ml/min/1.73 m2 72. The core specialist heart failure multidisciplinary team (MDT) should work in collaboration with the primary care team, and should include: a lead physician with a subspecialty interest in heart failure (usually a consultant cardiologist) who is responsible for making the clinical diagnosis a specialist heart failure nurse a healthcare professional with expertise in specialist prescribing for heart failure. 73.


The core specialist heart failure multidisciplinary team (MDT) should work in collaboration with the primary care team, and should include: a lead physician with a subspecialty interest in heart failure (usually a consultant cardiologist) who is responsible for making the clinical diagnosis a specialist heart failure nurse a healthcare professional with expertise in specialist prescribing for heart failure. 73. The specialist heart failure MDT should directly involve, or refer people to, other services, including rehabilitation services, and tertiary and palliative care, as needed. [2018] 74. The specialist heart failure MDT should: diagnose heart failure give information to people newly diagnosed with heart failure (see manage newly diagnosed, recently decompensated or advanced heart failure (NYHA [New York Heart Association] class III to IV) heart failure optimise treatment start new medicines that need specialist supervision continue to manage care after an interventional procedure such as implantation of a cardioverter defibrillator or cardiac resynchronisation device manage heart failure that is not responding to treatment. [2018] 75. The primary care team should carry out the following for people with heart failure at all times, including periods when the person is also receiving specialist heart failure from the MDT: Chronic Heart Failure Guideline summary NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 ensure effective communication links between different care settings and clinical services involved in the person s care lead a full review of the person s heart failure care, which may form part of a long-term conditions review recall the person at least every 6 months and update the summary and clinical record ensure that changes to the clinical record are understood and agreed by the person with heart failure and shared with the specialist heart failure MDT arrange access to specialist heart failure services if needed.


ISBN: 978-1-4731-3093-7 ensure effective communication links between different care settings and clinical services involved in the person s care lead a full review of the person s heart failure care, which may form part of a long-term conditions review recall the person at least every 6 months and update the summary and clinical record ensure that changes to the clinical record are understood and agreed by the person with heart failure and shared with the specialist heart failure MDT arrange access to specialist heart failure services if needed. [2018] For recommendations on the diagnosis and management of acute heart failure see NICE s guideline on acute heart failure. 76. People 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 the wishes of the person and their family or carer, and the level of care and support that can be provided in the community. [2003] 77. The primary care team working within the specialist heart failure MDT should take over routine management of heart failure as soon as it has been stabilised and its management optimised. [2018] 78. The specialist heart failure MDT should write a summary for each person with heart failure that includes: diagnosis and aetiology medicines prescribed, monitoring of medicines, when medicines should be reviewed and any support the person needs to take the medicines functional abilities and any social care needs social circumstances, including carers' needs. [2018] 79. The summary should form the basis of a care plan for each person, which should include.


The summary should form the basis of a care plan for each person, which should include. plans for managing the person s heart failure, including follow-up care, rehabilitation and access to social care symptoms to look out for in case of deterioration a process for any subsequent access to the specialist heart failure MDT if needed contact details for: a named healthcare coordinator (usually a specialist heart failure nurse) local heart failure specialist care providers, for urgent care or review additional sources of information for people with heart failure. [2018] 80. Give a copy of the care plan to the person with heart failure, ther family or carer if appropriate, and all health and social care professionals involved in their care. [2018] 81. When giving information to people with heart failure, follow the recommendations in the NICE guideline on patient experience in adult NHS Chronic Heart Failure Guideline summary NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 82. Discuss the person's prognosis in a sensitive, open and honest manner. Be frank about the uncertainty in predicting the course of their heart failure. Revisit this discussion as the person's condition evolves. [2018] 83. Provide information whenever needed throughout the person s care. [2018] 84. Consider training in advanced communication skills for all healthcare professionals working with people who have heart failure. [2018] 85. The specialist heart failure MDT should offer people newly diagnosed with heart failure an extended first consultation, followed by a second consultation, to take place within 2 weeks if possible. At each consultation: discuss the person s diagnosis and prognosis explain heart failure terminology discuss treatments address the risk of sudden death, including any misconceptions about that risk encourage the person and their family or carers to ask any questions they have. [2018] 86.


At each consultation: discuss the person s diagnosis and prognosis explain heart failure terminology discuss treatments address the risk of sudden death, including any misconceptions about that risk encourage the person and their family or carers to ask any questions they have. [2018] 86. Do not offer long-term home oxygen therapy for advanced heart failure. Be aware that long-term home oxygen therapy may be offered for comorbidities, such as for some people with chronic obstructive pulmonary disease (see section 1.2.5 on oxygen in the NICE guidline on chronic obstructive pulmonary disease in over 16s. [2018] 87. If it is thought that a person may be entering the last 2 to 3 days of life, follow the NICE guideline on care of dying adults in the last days of life. See NICE s technology appraisal guidance on implantable cardioverter defibrillators and cardiac resynchronisation therapy for arrhythmias and heart failure. 88. When discussing implantation of a cardioverter defibrillator: explain the risks, benefits and consequences of cardioverter defibrillator implantation, following the principles on shared decision making in the NICE guideline on patient experience in adult NHS services ensure the person knows that the defibrillator can be deactivated without affecting any cardiac resynchronisation or pacing, and reactivated later explain the circumstances in which deactivation might be offered discuss and dispel common misconceptions about the function of the device and the consequences of deactivation provide the person and, if they wish, their family or carers with written information covering the information discussed. [2018] 89. Review the benefits and potential harms of a cardioverter defibrillator remaining active in a person with heart failure: at each 6-monthly review of their heart failure care whenever their care goals change as part of advance care planning if it is thought they are nearing the end of life.


[2018] 89. Review the benefits and potential harms of a cardioverter defibrillator remaining active in a person with heart failure: at each 6-monthly review of their heart failure care whenever their care goals change as part of advance care planning if it is thought they are nearing the end of life. [2018] Chronic Heart Failure Guideline summary NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 90. Do not use prognostic risk tools to determine whether to refer a person with heart failure to palliative care services. [2018] 91. If the symptoms of a person with heart failure are worsening despite optimal specialist treatment, discuss their palliative care needs with the specialist heart failure MDT and consider a needs assessment for palliative care. [2018] 92. People with heart failure and their families or carers should have access to professionals with palliative care skills within the heart failure team. [2003] 1.2 Diagnostic algorithm Figure 1: Diagnostic algorithm Chronic Heart Failure Guideline summary NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 1.3 Therapeutic algorithm Figure 2: Therapeutic algorithm 1.4 Key research recommendations Heart Failure diagnosed by the specialist If symptoms persist despite optimal first line therapy, seek specialist advice and consider one or more of the following options Manage co-morbidconditions such as high blood pressure, atrial fibrillation ischaemic heart disease, and diabetes mellitus in line with NICE guidance 1 Please refer to CG180 for recommendations on the use of digoxin in patients with atrial fibrillation. For more information on drug treatment and monitoring see the NICE guideline on Chronic Heart Failure: assessment and management (CGX). Please refer to the NICE guidelines on chronic kidney disease (CG182) and on acute kidney injury (CG169).


Please refer to the NICE guidelines on chronic kidney disease (CG182) and on acute kidney injury (CG169). Cardiac re-synchronisation therapy (CRT-P/D) in accordance with Heart Failure with Reduced Ejection Fraction (HFREF) Consider ARB if intolerant of ACEI Consider hydralazine & nitrate if intolerant of ACEI & ARB First line: Offer ACEI and BB Offer an MRA if symptoms continue Replace ACEI (or ARB) with Sacubitril-Valsartan in accordance ICD in accordance with Specialist re-assessment Offer diuretics for the relief of congestive symptoms and fluid retention All heart failure: Offer a personalised, exercise-based cardiac rehabilitation programme, unless condition is unstable Add Ivabradine if in sinus rhythm, with a HR >75 bpm and LVEF <35% in accordance Add Hydralazine & nitrate (especially if of African/Caribbean descent) Digoxin for If the person s eGFR is 30-45 ml/min/1.73 m2, consider lower doses and/or slower titration of dose of ACE inhibitors or ARBs, mineralocorticoid receptor antagonists, sacubitril valsartan, and digoxin. If the person s eGFR is <30 ml/min/1.73 m2, consider liaising with a renal physician. Heart Failure with Preserved Ejection Fraction (HFPEF) Chronic Heart Failure Guideline summary NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 What is the optimal NT-proBNP threshold for the diagnosis of heart failure in people with atrial fibrillation? What are the optimal NT-proBNP thresholds for diagnosing heart failure in people with IIIb, IV or V chronic kidney disease? What is the optimal threshold for NT-proBNP for the diagnosis of heart failure in people with suspected heart failure: 400 ng/ml or 125 ng/ml? What is the optimal imaging technique for the diagnosis of heart failure? No recommendation No recommendation In people with advanced heart failure and significant peripheral fluid overload, what is the clinical and cost effectiveness of oral, subcutaneous and intravenous diuretic therapy in the community?


No recommendation No recommendation In people with advanced heart failure and significant peripheral fluid overload, what is the clinical and cost effectiveness of oral, subcutaneous and intravenous diuretic therapy in the community? What is the most accurate prognostic risk toos in predicting 1 year mortality from heart failure at specific clinically relevant thresholds (for example, sensitivity, specificity, negative predictive value and positive predictive value at a threshold of 50% risk of mortality at 1 year)? Chronic Heart Failure Introduction NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 2.1 Diagnosis and definition of chronic heart failure Heart failure is a common complex clinical syndrome of symptoms and signs caused by impairment of the heart s action as a pump supporting the circulation 11, 74, 337 . It is caused by structural or functional abnormalities of the heart. The demonstration of objective evidence of these cardiac abnormalities is necessary for the diagnosis of heart failure to be made. The symptoms most commonly encountered are breathlessness (exertional dyspnoea, orthopnoea and paroxysmal nocturnal dyspnoea), fatigue, and oedema. Signs in heart failure could be due to pulmonary and systemic congestion, or the structural abnormalities either causing or caused by heart failure. There is no single diagnostic test for heart failure, and diagnosis relies on clinical judgement based on a combination of history, physical examination and appropriate investigations. Patients may present acutely with heart failure45 which is the subject of separate guidance (NICE Acute Heart Failure: diagnosis and management. Clinical Guideline 187) 234 , or have a more insidious presentation. Most acute presentations are due to patients with chronic heart failure suffering an acute decompensation ( 65%), while the remainder are new presentations of acute heart failure ( 35%).


Most acute presentations are due to patients with chronic heart failure suffering an acute decompensation ( 65%), while the remainder are new presentations of acute heart failure ( 35%). Patients identified in the community with heart failure have breathlessness as their most common complaint. However, patients often consult their doctor with multiple non-specific symptoms such as fatigue, or with symptoms in the context of other long-term co-morbidities which can make the recognition of heart failure more challenging 45 . 2.2 Clinical context Around 920,000 people in the UK today have been diagnosed with heart failure 74 . Both the incidence and prevalence of heart failure increase steeply with age, with the average age at first diagnosis being 77 years.While around 1 in 35 people aged 65 74 years has heart failure, this increases to about 1 in 15 of those aged 75 84 years, and to just over 1 in 7 in those aged above 85 years. Less data exists about heart failure in younger age groups but there is increasing recognition that this condition affects a proportion of patients aged less than 65 years 371 . The prevalence of heart failure is rising overall despite improvements in care through a combination of improved survival of people with ischaemic heart disease, more effective treatments for heart failure, and the effects of population ageing 74 .The recent rise in the prevalence of heart failure with preserved left ventricular ejection fraction parallels the rise in the prevalence of obesity and allied co-morbidities of hypertension, and diabetes mellitus 166, 353 . The most common cause of heart failure in the UK is coronary artery disease. Other heart failure admissions are often associated with atrial fibrillation or heart valve disease as well with presentations of cardiomyopathies and myocarditis.


Other heart failure admissions are often associated with atrial fibrillation or heart valve disease as well with presentations of cardiomyopathies and myocarditis. Heart failure commonly co-exists with other co-morbidities including hypertension, diabetes, ischaemic heart diseases, atrial fibrillation and chronic obstructive pulmonary disease 74 . The risk of heart failure is higher in men than in women in all age groups, but there are more women than men with heart failure due to population demographics. Heart failure is also more common in groups with higher indices of social deprivation. There are few reliable data for other ethnic groups but people of African or Afro-Caribbean origin are more likely to develop heart failure due to hypertension58 rather than coronary artery disease, whereas those of Asian origin have a greater risk of developing heart failure due to coronary artery disease often associated with obesity and diabetes mellitus39 . The importance of heart failure was recognised by the All Party Parliamentary Group on Heart Disease Inquiry into Living with Heart Failure which issued 10 suggestions for improvement in care for patients with heart failure9 . Heart failure accounts for a total of 1 million inpatient bed days 2% of all NHS inpatient bed-days and 5% of all emergency medical admissions to hospital. Hospital Chronic Heart Failure Introduction NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 admissions due to heart failure are projected to rise by 50% over the next 25 years largely due to ageing of the population. This is despite a progressive decline in the age-adjusted hospitalisation rates at 1-1.5% per annum since 1992-1993235 . It is estimated that the total annual cost of heart failure to the NHS is around 2% of the total NHS budget: approximately 70% of this total is due to the .


It is estimated that the total annual cost of heart failure to the NHS is around 2% of the total NHS budget: approximately 70% of this total is due to the . Admissions tend to be protracted: The median length of stay is 6-9 days depending on the requirement for additional specialist cardiology management235 . Readmissions are common: about 1 in 4 patients are readmitted in 3 months. Associated co-morbidities account for a substantial proportion of admissions of people with a diagnosis of heart failure45 . The costs increase with disease severity, with the healthcare costs for patients with the most severe symptoms between 8 and 30 times greater than those with mild symptoms35 . Patients on GP heart failure registers, representing prevalent cases of heart failure, continue to be at significant mortality risk, with a ten-year survival of 27% as compared to 75% in the age- and sex- matched general population in 2009329 .The prognosis is poorer in patients with co-morbidities329 and may be similar to patients with cancer20 . On average, a GP will look after 30 patients with heart failure and suspect a new diagnosis of heart failure in, perhaps, 10 patients annually. Those who work in more deprived areas are likely to have more cases. The cost of GP consultations has been estimated at 50 million per year, with an additional 50 million for GP referrals to outpatient clinics. In addition, community-based drug therapy costs the NHS around 150 million per year. The recent National UK Heart Failure audit of acute heart failure suggests continuing improvements in heart failure diagnosis and management. In-patient mortality has fallen from 15% in 2009 to 8.9% in 2016 leading to more patients requiring long-term care in the community235 .


In-patient mortality has fallen from 15% in 2009 to 8.9% in 2016 leading to more patients requiring long-term care in the community235 . Despite this 20% of patients are readmitted within 30 days of initial admission and 50% within one year though commonly due to non-heart failure causes45 .Younger patients do better, as do patients reviewed by specialist as opposed to general services.Rates of drug prescription have increased, but one-year mortality remains significant. The evidence suggests a trend of improved prognosis for heart failure in the last 10 years74 but this is not found in all studies331 . Patients indicate that their management of heart failure impacts beyond just the clinical management with effects on social relationships, emotional well-being and psychological status. As well as NHS costs, heart failure places a burden on other agencies such as social services and the benefits system, and of course on the patients with heart failure, their families and carers. For patients and their carers, the costs are more difficult to quantify, but the burden is both financial and via adverse effects on their quality of life. The financial costs of heart failure to the patient and family arise from prescription charges (in patients under the age of 60), attendance at GP surgeries and outpatient clinics, hospital stays, modifications to the home and loss of earnings due to absence from work or loss of employment thus leading to adverse pressures on the family. Quality of life is affected by the physical limitations imposed by the condition, the social limitations that follow from this and the emotional problems that may also arise146 . These symptoms can be caused by the disease itself, by co-morbidities, or can result from the side effects of treatment.


These symptoms can be caused by the disease itself, by co-morbidities, or can result from the side effects of treatment. Pharmacological and non- pharmacological treatments can improve patients quality of life, both in terms of physical functioning and well-being. 2.3 Definition of a specialist The term specialist is applicable to a wide range of healthcare professionals; however, within the context of this guideline, the term specialist is used in relation to establishing the diagnosis of heart failure and more complex decisions on the management of heart failure and its multiple causes. Throughout this guideline the term specialist denotes a physician with sub-specialty interest in heart failure (often a consultant cardiologist) who leads a specialist multidisciplinary heart failure team of professionals with appropriate competencies from primary and secondary care (see chapter Chronic Heart Failure Introduction NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 12). The team will involve, where necessary, other services (such as rehabilitation, other acute medical specialities, older person s care and palliative care) in the care of individual patients. Unless otherwise specified, within this guideline specialist assessment or management refers to assessment or management by this specialist multidisciplinary heart failure team. The team will decide who is the most appropriate team member to address any particular clinical problem. 2.4 Definitions used in the guideline Initial research into heart failure concentrated on patients with heart failure due to impaired contraction of the left ventricle, also known as left ventricular systolic dysfunction (LVSD). Consequently, therapeutic interventions have primarily been tested in this group of patients. Over the last 20 years it has become evident that almost half the patients with clinical signs of heart failure do not have LVSD. This proportion is increasing 353 .


Over the last 20 years it has become evident that almost half the patients with clinical signs of heart failure do not have LVSD. This proportion is increasing 353 . Despite the prevalence of the latter group, there are far less diagnostic or intervention trials for this group, compared to those with LVSD. This distinction into two categories of heart failure have led to a classification system based on left ventricular ejection fraction. The Guideline Development Group (GDG) agreed on the following definitions: Heart failure with reduced ejection fraction (HFREF) This group of patients is characterised by heart failure with a left ventricular ejection fraction by echocardiography of less than 40%. Heart failure with preserved ejection fraction (HFPEF) This group of patients with heart failure have a left ventricular ejection fraction greater than 50%, o no alternative cause for the syndrome, o the presence of a non-dilated left ventricle; evidence of structural remodelling (left ventricular hypertrophy or dilated left atrium); or diastolic dysfunction through imaging o and have abnormal biomarkers. The GDG recognises that the two terms HFREF and HFPEF have several limitations. These include the variability of the left ventricular ejection fraction measured by different imaging modalities, and the lack of universal agreement on the threshold of ejection fraction at which these are defined or the exact definition of HFPEF. The GDG also recognised the proposal of another class as heart failure with mid-range ejection fraction (HFMREF). This proposal has not been fully clinically validated and remains the topic of further research 150, 354 . The GDG reviewed the available biomarkers for diagnosis of heart failure. Assays for both B-type natriuretic peptide (BNP) and NT-pro-BNP are commonly available. Other biomarkers have been identified but their utility is unclear.


Other biomarkers have been identified but their utility is unclear. It considered that any marker chosen should be widely available, have an extensive evidence base, and good performance characteristics including high stability in patient samples given transfer times between primary care and central laboratory facilities. Though current practice favours the use of biomarkers for diagnosis rather than monitoring their future use cannot be predicted. Thus, the ability to interconvert between assays based on the same biomarker and the ability to clearly define baseline levels to allow long-term management by monitoring would be prudent to maintain. After consideration of the available assays222 , their performance and and recent publications that inform the rest of the guideline the GDG decided that NT-proBNP should be the favoured biomarker as it was more commonly used, more stable, did not require additional laboratory specimens for ideal performance248 and did not suffer from potential confounding of interpretation by novel therapies (e.g. sacubitril-valsartan)303 . Chronic Heart Failure Introduction NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 2.5 Rationale for the update This guideline is a partial update of NICE Guideline No 108: Chronic Heart Failure in adults . The 2010 guidelines offered advice on best practice for the care of adult patients (aged 18 years or older) who have symptoms or a diagnosis of chronic heart failure. Since and North American374 guidelines, based on new high-quality evidence from randomised controlled trials in diagnosis, treatment and monitoring have been published. A partial update of the existing NICE guideline is necessary to ensure that the recommendations take into account the new evidence available. Diagnosis of heart failure depends on clinical symptoms and signs with imaging usually echocardiography - and increasingly laboratory measured biomarkers such as natriuretic peptides (chapter 5).


Diagnosis of heart failure depends on clinical symptoms and signs with imaging usually echocardiography - and increasingly laboratory measured biomarkers such as natriuretic peptides (chapter 5). Technological progress has led to availability of further imaging technologies e.g. cardiac magnetic resonance imaging (chapter 5) and biomarkers which might be used in diagnosis or for monitoring the efficacy and titration of therapies (chapter 8). The National Heart Failure audit highlights the roles that beta-blocker (chapter 6) and mineralocorticoid receptor antagonist (MRA) therapy (chapter 6) are playing in management of heart failure. The evidence base for these treatments has increased over the last 10 years. Despite the high prevalence of ischaemic heart disease in patients with heart failure the role of coronary intervention in patients with heart failure remains unclear (chapter 6). The high incidence of iron deficiency and anaemia in patients with heart failure has prompted trials of iron therapy in heart failure (chapter 6). Patients with co-morbidities have a worse prognosis and some co-morbidities such as atrial fibrillation (chapter 6) or chronic kidney disease can influence the management of heart failure (chapter 6). Non-pharmacological interventions also have a substantial and under-recognised role to play in the management of heart failure. Evidence has accumulated for better outcomes in patients receiving care from cardiology services including specialist heart failure nurses (chapter 9) and in those able to access rehabilitation (chapter 7). The increasing move of complex care from hospital to primary care places a greater emphasis on communication and processes for transition of care (chapter 9) and the ability to manage symptomatic relief in community settings (chapter 10). Developments in information technology and in the use of telephone-based and direct telemonitoring technologies have the potential to further improve delivery of care (chapter 8) 241 .


Developments in information technology and in the use of telephone-based and direct telemonitoring technologies have the potential to further improve delivery of care (chapter 8) 241 . Heart failure is a progressive condition but access to palliative care services remains patchy, with unclear referral criteria (chapter 10), unclear policies on deactivation of implanted devices (chapter 10) and on the use of ancillary therapies such as diuretic regimes (chapter 10) or domiciliary oxygen (chapter 10). The guideline update is intended for use by the following people or organisations: All healthcare professionals People with chronic heart failure and their carers Patient support groups Commissioning organisations Service providers Chronic Heart Failure Development of the guideline NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 3 Development of the guideline 3.1 What is a NICE guideline? NICE guidelines are recommendations for the care of individuals in specific clinical conditions or circumstances within the NHS from prevention and self-care through primary and secondary care to more specialised services. These may also include elements of social care or public health measures. We base our guidelines on the best available research evidence, with the aim of improving the quality of healthcare. We use predetermined and systematic methods to identify and evaluate the evidence relating to specific review questions. NICE guidelines can: provide recommendations for the treatment and care of people by health professionals be used to develop standards to assess the clinical practice of individual health professionals be used in the education and training of health professionals help patients to make informed decisions improve communication between patient and health professional. While guidelines assist the practice of healthcare professionals, they do not replace their knowledge and skills. We produce our guidelines using the following steps: A guideline topic is referred to NICE from NHS England.


We produce our guidelines using the following steps: A guideline topic is referred to NICE from NHS England. Stakeholders register an interest in the guideline and are consulted throughout the development process. The scope is prepared by the National Guideline Centre (NGC). The NGC establishes a guideline committee. A draft guideline is produced after the group assesses the available evidence and makes recommendations. There is a consultation on the draft guideline. The final guideline is produced. The NGC and NICE produce a number of versions of this guideline: The full guideline contains all the recommendations, plus details of the methods used and the underpinning evidence. The NICE guideline lists the recommendations. NICE Pathways brings together all connected NICE guidance. This version is the full version. The other versions can be downloaded from NICE at www.nice.org.uk. NICE received the remit for this guideline from NHS England. NICE commissioned the NGC to produce the guideline. The remit for this guideline is: To develop a clinical guideline on the management of chronic heart failure in adults in primary and secondary care. Chronic Heart Failure Development of the guideline NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 3.3 Who developed this guideline? A multidisciplinary guideline committee comprising health professionals and researchers as well as lay members developed this guideline (see the list of guideline committee members and the acknowledgements). The National Institute for Health and Care Excellence (NICE) funds the National Guideline Centre (NGC) and thus supported the development of this guideline. The committee was convened by the NGC and chaired by Anthony Wierzbicki in accordance with guidance from NICE. The group met approximately every 6 weeks during the development of the guideline.


The group met approximately every 6 weeks during the development of the guideline. At the start of the guideline development process all committee members declared interests including consultancies, fee-paid work, shareholdings, fellowships and support from the healthcare industry. At all subsequent committee meetings, members declared arising conflicts of interest. Members were either required to withdraw completely or for part of the discussion if their declared interest made it appropriate. The details of declared interests and the actions taken are shown in appendix L. Staff from the NGC provided methodological support and guidance for the development process. The team working on the guideline included a project manager, systematic reviewers (research fellows), health economists and information specialists. They undertook systematic searches of the literature, appraised the evidence, conducted meta-analysis and cost-effectiveness analysis where appropriate and drafted the guideline in collaboration with the committee. 3.3.1 What this guideline covers Groups that will be covered Adults (18 and over) with symptoms or a diagnosis of chronic heart failure (including heart failure with reduced ejection fraction and heart failure with preserved ejection fraction). Areas from the published guideline that will be updated Diagnosing heart failure. o Role of circulating biomarkers (including natriuretic peptides). o Echocardiography and cardiac MRI. Managing chronic heart failure. o Initiation and sequencing of pharmacological therapies including: Isosorbide/hydralazine. Angiotensin-II receptor antagonists (ARBs). Mineralocorticoid receptor antagonists o Fluid balance (optimum fluid and salt intake). Rehabilitation (including Home-based rehabilitation packages that include an exercise element). Monitoring heart failure. o Role of biomarkers (including natriuretic peptides). o Role of echocardiography. o Distance monitoring including telemonitoring. o Self-monitoring. Referral for invasive procedures: o Coronary revascularisation (including coronary artery bypass graft and angioplasty). Chronic Heart Failure Development of the guideline NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Referral and approach to care.


Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Referral and approach to care. o Heart failure multidisciplinary team. o Transfer of care between secondary and primary care services. Information and support. o Information and support on diagnosis and prognosis for people with chronic heart failure, their families and carers. Supportive and palliative care. o Domiciliary oxygen therapy. o Parenteral and intravenous diuretics. o Criteria for withdrawing treatment and device inactivation. Areas not in the published guideline that will be included in the update How to manage chronic heart failure in different subgroups: o People with iron deficiency. o People with chronic kidney disease (estimated glomerular filtration rate [eGFR] less than with or without markers of kidney damage). o People with chronic heart failure and secondary atrial fibrillation. o People aged over 75. Pharmacological therapies. o Beta-blockers in people with chronic heart failure and secondary atrial fibrillation. Palliative care. o Referral to palliative care. o Delivery of diuretics Monitoring heart failure. o Role of cardiac MRI. For further details please refer to the scope in appendix L and the review questions in section 4.1. 3.3.2 What this guideline does not cover Areas from the published guideline that will not be updated Symptoms and signs in diagnosing heart failure. Clinical review and monitoring of serum digoxin. Lifestyle. o Sexual activity, vaccination and air travel. Areas from the published guideline that will be removed General. o Age. o Gender. Pharmacological agents. o Aspirin. Chronic Heart Failure Development of the guideline NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 o Statins. Heart failure caused by valve disease. Management of depression and anxiety. Benefit of other therapies such as homeopathy, reflexology, hydrotherapy, crystal therapy and acupuncture. Referral for invasive procedures. o Implantable cardiac defibrillators. Valve surgery. Non-NHS agencies. Lifestyle.


Referral for invasive procedures. o Implantable cardiac defibrillators. Valve surgery. Non-NHS agencies. Lifestyle. o Smoking and alcohol. 3.3.3 Relationships between the guideline and other NICE guidance NICE guidance that will be updated by this guideline: Chronic heart failure in in adults: management (2010) NICE guidline CG108 NICE technology appraisals to be incorporated in this guidance: Ivabradine for treating chronic heart failure (2012) NICE technology appraisal guidance 267. Sacubitril valsartan for treating symptomatic chronic heart failure with reduced ejection fraction (2016) NICE technology appraisal [TA388] Related NICE technology appraisals: Implantable cardioverter defibrillators and cardiac resynchronisation therapy for arrhythmias and heart failure (2014) NICE technology appraisal guidance [TA314] Related NICE intervenetional procedures guidance Subcutaneous implantable cardioverter defibrillator insertion for preventing sudden cardiac death Related NICE guidelines: Medicines optimisation (2015) NICE guideline NG5 Patient experience in adult NHS services (2012) NICE guideline CG138 Medicines adherence (2009) NICE guideline CG76 Acute heart failure: diagnosis and management (2014) Nice guideline [CG187] Chronic Heart Failure Methods NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 This chapter sets out in detail the methods used to review the evidence and to develop the recommendations that are presented in subsequent chapters of this guideline. This guidance was developed in accordance with the methods outlined in the NICE guidelines manual, 2014 version.236 Sections 4.1 to 4.3 describe the process used to identify and review clinical evidence (summarised in Figure 3), sections 4.2 and 4.4 describe the process used to identify and review the health economic evidence, and section 4.5 describes the process used to develop recommendations.


This guidance was developed in accordance with the methods outlined in the NICE guidelines manual, 2014 version.236 Sections 4.1 to 4.3 describe the process used to identify and review clinical evidence (summarised in Figure 3), sections 4.2 and 4.4 describe the process used to identify and review the health economic evidence, and section 4.5 describes the process used to develop recommendations. Figure 3: Step-by-step process of review of evidence in the guideline 4.1 Developing the review questions and outcomes Review questions were developed using a PICO framework (population, intervention, comparison and outcome) for intervention reviews; using a framework of population, index tests, reference standard and target condition for reviews of diagnostic test accuracy; using population, presence or absence of factors under investigation (for example prognostic factors) and outcomes for prognostic reviews; and using a framework of population, setting and context for qualitative reviews. This use of a framework guided the literature searching process, critical appraisal and synthesis of evidence, and facilitated the development of recommendations by the guideline committee. The review questions were drafted by the NGC technical team and refined and validated by the committee. The questions were based on the key clinical areas identified in the scope (appendix L). A total of 26 review questions were identified. Chronic Heart Failure Methods NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Full literature searches, critical appraisals and evidence reviews were completed for all the specified review questions. Table 1: Review questions Chapter Type of review Review questions Outcomes 5 Diagnostic In people with suspected heart failure, what thresholds of pro-B-type natriuretic peptide (NT-proBNP) and B- type natriuretic peptide (BNP) are most accurate in identifying heart failure (as indicated by the reference standard)?


Table 1: Review questions Chapter Type of review Review questions Outcomes 5 Diagnostic In people with suspected heart failure, what thresholds of pro-B-type natriuretic peptide (NT-proBNP) and B- type natriuretic peptide (BNP) are most accurate in identifying heart failure (as indicated by the reference standard)? Diagnostic accuracy of BNP and NT-proBNP: 2x2 tables Specificity Sensitivity PPV/NPV ROC curve or Area under Curve 5 Diagnostic RCT In people with suspected heart failure, what is the clinical and cost effectiveness of N-terminus pro-B-type natriuretic peptide (NT-proBNP) compared to B-type natriuretic peptide (BNP), when each is followed by the appropriate patient pathway, in order to improve patient outcomes? Efficacy outcomes: All-cause mortality Quality of life Unplanned hospitalisation Process outcomes: Number of people receiving echocardiography, i.e., including people who may not have needed it such as those with false positive results Repeat testing / additional testing Secondary accuracy outcomes: Sensitivity / specificity and other test accuracy measures 5 Diagnostic In people with suspected heart failure who also have atrial fibrillation, what thresholds of N-terminus pro-B-type natriuretic peptide (NT-proBNP) and B- type natriuretic peptide (BNP) are most accurate in identifying heart failure (as indicated by the reference standard)? Diagnostic accuracy of BNP and NT-proBNP: 2x2 tables Specificity Sensitivity PPV/NPV ROC curve or Area under Curve 5 Diagnostic RCT In people with suspected heart failure who also have atrial fibrillation, what is the clinical and cost effectiveness of N- terminus pro-B-type natriuretic peptide (NT-proBNP) compared to B-type natriuretic peptide (BNP), when each is followed by the appropriate patient pathway, in order to improve patient outcomes? Efficacy outcomes: All-cause mortality Quality of life Unplanned hospitalisation Process outcomes: Number of people receiving echocardiography, i.e.


Efficacy outcomes: All-cause mortality Quality of life Unplanned hospitalisation Process outcomes: Number of people receiving echocardiography, i.e., including people who may not have needed it such as those with false positive results Repeat testing / additional testing Secondary accuracy outcomes: Sensitivity / specificity and other test accuracy measures 5 Diagnostic In people with suspected heart failure who also have chronic kidney disease, Diagnostic accuracy of BNP and NT-proBNP: Chronic Heart Failure Methods NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Chapter Type of review Review questions Outcomes what thresholds of N-terminus pro-B- type natriuretic peptide (NT-proBNP) and B-type natriuretic peptide (BNP) are most accurate in identifying heart failure (as indicated by the reference standard)? 2x2 tables Specificity Sensitivity PPV/NPV ROC curve or Area under Curve 5 Diagnostic RCT In people with suspected heart failure who also have chronic kidney disease, what is the clinical and cost effectiveness of N-terminus pro-B-type natriuretic peptide (NT-proBNP) compared to B-type natriuretic peptide (BNP), when each is followed by the appropriate patient pathway, in order to improve patient outcomes? Efficacy outcomes: All-cause mortality Quality of life Unplanned hospitalisation Process outcomes: Number of people receiving echocardiography, i.e., including people who may not have needed it such as those with false positive results Repeat testing / additional testing Secondary accuracy outcomes: Sensitivity / specificity and other test accuracy measures 5 Intervention In people with heart failure what is the clinical and cost effectiveness of cardiac MRI followed by the appropriate patient pathway?


, including people who may not have needed it such as those with false positive results Repeat testing / additional testing Secondary accuracy outcomes: Sensitivity / specificity and other test accuracy measures 5 Intervention In people with heart failure what is the clinical and cost effectiveness of cardiac MRI followed by the appropriate patient pathway? Critical outcomes: All-cause mortality (time to event) Health-related quality of life at 12 months (continuous) Unplanned hospitalisation (total number of events (rate ratio)) Important outcomes: Adverse events related to test (non-specific fibrosis in the presence of renal dysfunction) Reclassification of specific HF aetiology (including ability to classify previous unclassified patients) Change in management HF medication use HF advanced therapy use, including disease specific therapies Repeat testing / additional testing 6 Intervention What is the clinical and cost effectiveness of salt and/or fluid restriction in people with heart failure? Critical outcomes: Quality of life at 12 months (Continuous) Unplanned hospitalization (Count rate) Important outcomes: Change in weight at 12 months Chronic Heart Failure Methods NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Chapter Type of review Review questions Outcomes (Continuous) Change in oedema at 12 months (Continuous) Change in sodium level (Continuous)(in the low baseline sodium strata only) Adverse events - Renal function at 12 months (Dichotomous) Adverse events - Hyperkalaemia at 12 months (Dichotomous) 6 Intervention What is the clinical and cost effectiveness of beta-blockers in the management of chronic heart failure in people with heart failure with reduced ejection fraction (HFREF) and atrial fibrillation? Critical outcomes: All-cause mortality Health-related quality of life Unplanned hospitalisation Important outcomes: Other adverse events (stroke, bradycardia, hypotension) Improvement of NYHA class 6 Intervention What is the clinical and cost effectiveness of mineralocorticoid receptor antagonists in people with heart failure with preserved ejection fraction?


Critical outcomes: All-cause mortality Health-related quality of life Unplanned hospitalisation Important outcomes: Other adverse events (stroke, bradycardia, hypotension) Improvement of NYHA class 6 Intervention What is the clinical and cost effectiveness of mineralocorticoid receptor antagonists in people with heart failure with preserved ejection fraction? Critical outcomes: All-cause mortality Quality of life Unplanned hospitalisation Important outcomes: Improvement of NYHA class Adverse events - Renal function Adverse events Gynaecomastia Adverse events Hypotension Adverse events - Hyperkalaemia 6 Intervention What is the clinical and cost effectiveness of adding a mineralocorticoid receptor antagonist to existing standard first line treatment in people with heart failure with reduced ejection fraction? Critical outcomes: All-cause mortality Quality of life Unplanned hospitalisation Important outcomes: Improvement of NYHA class Adverse events - Renal function Adverse events Gynaecomastia Adverse events Hypotension Adverse events - Hyperkalaemia 6 Intervention What is the clinical and cost effectiveness of iron supplementation in people with chronic heart failure and iron deficiency? Critical outcomes: Mortality Quality of life Unplanned hospitalisation Important outcomes: Improvement in exercise Chronic Heart Failure Methods NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Chapter Type of review Review questions Outcomes tolerance Change in haemoglobin in anaemic patients Withdrawal due to adverse events/tolerability Adverse events (hypertension, anaphylaxis/hypersensitivity, stroke, gastrointestinal) 6 Intervention What is the clinical and cost effectiveness of pharmacological interventions for heart failure in people with heart failure who also have chronic kidney disease?


ISBN: 978-1-4731-3093-7 Chapter Type of review Review questions Outcomes tolerance Change in haemoglobin in anaemic patients Withdrawal due to adverse events/tolerability Adverse events (hypertension, anaphylaxis/hypersensitivity, stroke, gastrointestinal) 6 Intervention What is the clinical and cost effectiveness of pharmacological interventions for heart failure in people with heart failure who also have chronic kidney disease? Critical outcomes: All-cause mortality Quality of life Unplanned hospitalization Important outcomes: Renal function Adverse events - Bradycardia Adverse events - Arrhythmic events Adverse events - Progression to stage five kidney disease / unplanned dialysis Adverse events - Hypotension Adverse events - Hyperkalaemia 6 Intervention What is the clinical and cost effectiveness of coronary revascularisation with coronary artery bypass grafting or angioplasty in people with heart failure? Critical outcomes: All-cause mortality at 30 days (Time to event) All-cause mortality (Time to event) Quality of life at 12 months (Continuous) Unplanned hospitalisation at 12 months (Count rate) Important outcomes: Additional revascularisation events at 24 months (Count rate) Improvement of NYHA class at 12 months (Dichotomous) Improvement in ejection fraction at 12 months (Dichotomous) Adverse events - stroke at 12 months (Dichotomous) 7 Intervention What is the clinical and cost effectiveness of home-based versus centre-based rehabilitation (that includes an exercise element) for people with heart failure (HF)? Critical outcomes: All-cause mortality CV mortality Health-related quality of life All cause hospitalisation HF-related hospitalisation Important outcomes: Chronic Heart Failure Methods NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Chapter Type of review Review questions Outcomes Exercise capacity Adverse events (withdrawal from the exercise programme) Adherence (including maintenance of exercise/physical activity) Health service use 8 Intervention What is the clinical and cost effectiveness of biomarker-based monitoring, monitoring with cardiac MRI, and monitoring with repeated echocardiography in people with heart failure?


ISBN: 978-1-4731-3093-7 Chapter Type of review Review questions Outcomes Exercise capacity Adverse events (withdrawal from the exercise programme) Adherence (including maintenance of exercise/physical activity) Health service use 8 Intervention What is the clinical and cost effectiveness of biomarker-based monitoring, monitoring with cardiac MRI, and monitoring with repeated echocardiography in people with heart failure? Critical outcomes: Mortality (Time to event) Quality of life at 12 months (Continuous) Unplanned hospitalisation (all- cause) (Count rate) Important outcomes: Adverse events - hypotension (Dichotomous) Adverse events - hyperkalaemia (Dichotomous) Adverse events - renal function (Continuous) Adverse events - bradycardia (Dichotomous) Adverse events - arrhythmic events (Dichotomous) 8 Intervention What is the clinical and cost effectiveness of biomarker-based monitoring, monitoring with cardiac MRI, and monitoring with repeated echocardiography in people with heart failure who also have CKD? Critical outcomes: Mortality (Time to event) Quality of life at 12 months (Continuous) Unplanned hospitalisation (all- cause) (Count rate) Important outcomes: Adverse events - hypotension (Dichotomous) Adverse events - hyperkalaemia (Dichotomous) Adverse events - renal function (Continuous) Adverse events - bradycardia (Dichotomous) Adverse events - arrhythmic events (Dichotomous) 8 Intervention What is the clinical and cost effectiveness of biomarker-based monitoring, monitoring with cardiac MRI, and monitoring with repeated echocardiography in people with heart failure who also have atrial fibrillation? Critical outcomes: Mortality at during study (Time to event) Quality of life at 12 months (Continuous) Unplanned hospitalisation (all- cause) (Count rate) Important outcomes: Adverse events - hypotension Chronic Heart Failure Methods NICE 2018. All rights reserved. Subject to Notice of rights.


Critical outcomes: Mortality at during study (Time to event) Quality of life at 12 months (Continuous) Unplanned hospitalisation (all- cause) (Count rate) Important outcomes: Adverse events - hypotension Chronic Heart Failure Methods NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Chapter Type of review Review questions Outcomes (Dichotomous) Adverse events - hyperkalaemia (Dichotomous) Adverse events - renal function (Continuous) Adverse events - bradycardia (Dichotomous) Adverse events - arrhythmic events (Dichotomous) 8 Intervention What is the clinical and cost effectiveness of telemonitoring and self- monitoring using telephone technology, compared with usual care, in people with heart failure? Critical outcomes: All-cause mortality during study (dichotomous) Quality of life during study (continuous) All-cause hospitalisations during study (dichotomous) Important outcomes: Adherence to intervention 9 Intervention What competencies should be present in the multidisciplinary teams involved in the outpatient or community-based care of people with heart failure? Critical outcomes: All-cause mortality (Time to event) Quality of life (Continuous) Unplanned hospitalisation (Count rate) Important outcomes: Medicine optimization and adherence Dying in preferred place of death (for palliative care patients) Adverse events hypotension, hyperkalaemia, and renal function Patient and carer experience 9 Qualitative What are the experiences/preferences of staff and patients during transition between different heart failure care settings (including primary, secondary and community care)? Thematic analysis- information synthesised into main review findings. 9 Qualitative What are the information and support needs to be considered when communication a diagnosis and consequent prognosis, to people with heart failure, their families and carers? Thematic analysis- information synthesised into main review findings.


9 Qualitative What are the information and support needs to be considered when communication a diagnosis and consequent prognosis, to people with heart failure, their families and carers? Thematic analysis- information synthesised into main review findings. 10 Intervention Which route of administration of diuretics (intravenous (IV), subcutaneous or oral) is most clinically and cost effective in people with advanced heart failure who are in the community, including patients receiving Critical outcomes: Quality of life Unplanned hospitalization Important outcomes: Change in dyspnoea Chronic Heart Failure Methods NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Chapter Type of review Review questions Outcomes palliative care? Weight change / change in oedema Change in NYHA class Patient and carer satisfaction Time to death (survival) Successful administration of intervention 10 Intervention What is the effectiveness of domiciliary oxygen therapy in people with advanced heart failure? Critical outcomes: Quality of life at 2 weeks (Continuous) Change in dyspnea at 2 weeks (Continuous) Unplanned hospitalization at 4 weeks (Count rate) Unplanned hospitalization at 4 weeks (number of bed days) Patient and carer satisfaction 2 weeks (Continuous) Important outcomes: Change in exercise capacity at 2 weeks (Continuous) Change in NYHA class at 2 weeks (Continuous) 10 Qualitative What criteria should determine when to discuss defibrillator deactivation? Thematic analysis- information synthesised into main review findings. 10 Prognostic In adults with heart failure, which validated risk tools best identify patients with heart failure who are at increased risk of mortality in the short term (up to 1 year)?In adults with heart failure, which validated risk tools best identify patients with heart failure who are at increased risk of mortality in the short term (up to 1 year)?


10 Prognostic In adults with heart failure, which validated risk tools best identify patients with heart failure who are at increased risk of mortality in the short term (up to 1 year)?In adults with heart failure, which validated risk tools best identify patients with heart failure who are at increased risk of mortality in the short term (up to 1 year)? Area under the ROC curve (AUC or c-statistic) Sensitivity, specificity, negative predictive value, positive predictive value Predicted risk versus observed risk (calibration) Other outcomes e.g., D statistic and Brier score Reclassification 4.2 Searching for evidence 4.2.1 Clinical literature search Systematic literature searches were undertaken to identify all published clinical evidence relevant to the review questions. Searches were undertaken according to the parameters stipulated within the NICE guidelines manual 2014.236 Databases were searched using relevant medical subject headings, free-text terms and study-type filters where appropriate. Where possible, searches were restricted to papers published in English. Studies published in languages other than English were not reviewed. All searches were conducted in Medline, Embase, and The Cochrane Library. Additional subject specific databases were used for the qualitative reviews: CINAHL and PsychINFO. All searches were updated on 06.12.17. No papers published after this date were considered. Chronic Heart Failure Methods NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Search strategies were quality assured by cross-checking reference lists of highly relevant papers, analysing search strategies in other systematic reviews, and asking committee members to highlight any additional studies. Searches were quality assured by a second information specialist before being run.


Searches were quality assured by a second information specialist before being run. The questions, the study types applied, the databases searched and the years covered can be found in appendix N. The titles and abstracts of records retrieved by the searches were sifted for relevance, with potentially significant publications obtained in full text. These were assessed against the inclusion criteria. During the scoping stage, a search was conducted for guidelines and reports on the websites listed below from organisations relevant to the topic. Guidelines International Network database (www.g-i-n.net) National Guideline Clearing House (www.guideline.gov) National Institute for Health and Care Excellence (NICE) (www.nice.org.uk) National Institutes of Health Consensus Development Program (consensus.nih.gov) NHS Evidence Search (www.evidence.nhs.uk). Turning Research into Practice (TRIP (www.tripdatabase.com)) Royal College of General Practitioners (www.rcgp.org.uk) All references sent by stakeholders were considered. Searching for unpublished literature was not undertaken. The NGC and NICE do not have access to drug manufacturers unpublished clinical trial results, so the clinical evidence considered by the committee for pharmaceutical interventions may be different from that considered by the MHRA and European Medicines Agency for the purposes of licensing and safety regulation. 4.2.2 Health economic literature search Systematic literature searches were also undertaken to identify health economic evidence within published literature relevant to the review questions. The evidence was identified by conducting a broad search relating to heart failure in the NHS Economic Evaluation Database (NHS EED) and the Health Technology Assessment database (HTA) with no date restrictions (NHS EED ceased to be updated after March 2015). Additionally, the search was run on Medline and Embase using a health economic filter, from September 2009, to ensure recent publications that had not yet been indexed by the economic databases were identified.


Additionally, the search was run on Medline and Embase using a health economic filter, from September 2009, to ensure recent publications that had not yet been indexed by the economic databases were identified. The quality of life search was run on Medline and Embase using a quality of life filter, from January 2002. Where possible, searches were restricted to papers published in English. Studies published in languages other than English were not reviewed. The health economic search strategies are included in appendix N. The general heart failure economic search was updated on 6 December 2017. No papers published after this date were considered. 4.3 Identifying and analysing evidence of effectiveness Research fellows conducted the tasks listed below, which are described in further detail in the rest of this section: Identified potentially relevant studies for each review question from the relevant search results by reviewing titles and abstracts. Full papers were then obtained. Reviewed full papers against prespecified inclusion and exclusion criteria to identify studies that addressed the review question in the appropriate population, and reported on outcomes of interest (review protocols are included in appendix A). Chronic Heart Failure Methods NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Critically appraised relevant studies using the appropriate study design checklist as specified in the NICE guidelines manual.236 Prognostic studies were critically appraised using NGC checklists. Qualitative studies were critically appraised using the GRADE CERQual approach for rating confidence in the body of evidence as a whole and using an NGC checklist for the methodological limitations section of the quality assessment. Extracted key information about interventional study methods and results using Evibase , NGC s purpose-built software. Evibase produces summary evidence tables, including critical appraisal ratings.


Extracted key information about interventional study methods and results using Evibase , NGC s purpose-built software. Evibase produces summary evidence tables, including critical appraisal ratings. Key information about non-interventional study methods and results was manually extracted onto standard evidence tables and critically appraised separately (evidence tables are included in appendix F). Generated summaries of the evidence by outcome. Outcome data were combined, analysed and reported according to study design: o Randomised data were meta-analysed where appropriate and reported in GRADE profile tables. o Data from non-randomised studies were presented as a range of values in GRADE profile tables or meta-analysed if appropriate. o Prognostic data were meta-analysed where appropriate and reported in GRADE profile tables. o Diagnostic data studies were meta-analysed where appropriate or presented as a range of values in adapted GRADE profile tables o Qualitative data were synthesised across studies and presented as summary statements with accompanying GRADE CERQual ratings for each review finding. A sample of a minimum of 10% of the abstract lists of the first 3 sifts by new reviewers and those for complex review questions (for example, prognostic reviews) were double-sifted by a senior research fellow and any discrepancies were rectified. All of the evidence reviews were quality assured by a senior research fellow. This included checking: o papers were included or excluded appropriately o a sample of the data extractions o correct methods were used to synthesise data o a sample of the risk of bias assessments. 4.3.1 Inclusion and exclusion criteria The inclusion and exclusion of studies was based on the criteria defined in the review protocols, which can be found in appendix A. Excluded studies by review question (with the reasons for their exclusion) are listed in appendix I. The committee was consulted about any uncertainty regarding inclusion or exclusion.


The committee was consulted about any uncertainty regarding inclusion or exclusion. The key population inclusion criterion was: Adults (18 and older) with symptoms or a diagnosis of chronic heart failure (including heart failure with reduced ejection fraction and heart failure with preserved ejection fraction) The key population exclusion criterion was: Diagnostic screening for heart failure in people who are asymptomatic. People with isolated right heart failure. Heart failure in people having chemotherapy. Heart failure in people having treatment for HIV. Heart failure in women who are pregnant. Chronic Heart Failure Methods NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Conference abstracts were not included in any of the reviews. Literature reviews, posters, letters, editorials, comment articles, unpublished studies and studies not in English were excluded. 4.3.1.1 Saturation of qualitative studies Data extraction in qualitative reviews is a thorough process and may require more time compared to intervention reviews. It is common practice to stop extracting data once saturation has been reached. This is the point when no new information emerges from studies that match the review protocol. The remaining identified studies are, however, not directly excluded from the review as they nevertheless fit the criteria defined in the review protocol. Any studies for which data were not extracted due to saturation having been reached, but that fit the inclusion criteria of the protocol, were listed in the table for studies identified but not included due to saturation in the appendix for the qualitative evidence review. 4.3.2 Type of studies Randomised trials, non-randomised intervention studies, and other observational studies (including diagnostic or prognostic studies) were included in the evidence reviews as appropriate.


4.3.2 Type of studies Randomised trials, non-randomised intervention studies, and other observational studies (including diagnostic or prognostic studies) were included in the evidence reviews as appropriate. For most intervention reviews in this guideline, parallel randomised controlled trials (RCTs) were included because they are considered the most robust type of study design that can produce an unbiased estimate of the intervention effects. Crossover RCTs were not appropriate for any of the intervention reviews . In chronic conditions there is the possibility that the initial treatment permanently alters the disease or the process being investigated. The cardiac rehabilitation review was the exception where only data from the 1st period of cross-over trials was included, unless there was formal evidence of period effects in which case data from both 1st and 2nd periods was included. If non-randomised intervention studies were considered appropriate for inclusion (for example, in prognostic risk tool and diagnostic reviews) the committee stated a priori in the protocol that either certain identified variables must be equivalent at baseline or else the analysis had to adjust for any baseline differences. If the study did not fulfil either criterion it was excluded. Please refer to the review protocols in appendix A for full details on the study design of studies selected for each review question. For diagnostic review questions, diagnostic RCTs, cross-sectional studies and retrospective studies were included. For prognostic review questions, prospective and retrospective cohort studies were included. Case control studies were not included. Where data from non-randomised studies were included, the results for each outcome were presented separately for each study or meta-analysed if appropriate.


Where data from non-randomised studies were included, the results for each outcome were presented separately for each study or meta-analysed if appropriate. 4.3.3 Methods of combining clinical studies 4.3.3.1 Data synthesis for intervention reviews Where possible, meta-analyses were conducted using Cochrane Review Manager (RevMan5)283 software to combine the data given in all studies for each of the outcomes of interest for the review question. For some questions stratification was used, and this is documented in the individual review question protocols (see appendix A). Analysis of different types of data Chronic Heart Failure Methods NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 Dichotomous outcomes Fixed-effects (Mantel-Haenszel) techniques were used to calculate risk ratios (relative risk, RR) for the binary outcomes, which included: All-cause mortality Cardiovascular mortality Unplanned hospitalisation HF related hospitalisation Adverse events (for example stroke, bradycardia, hypotension, arrhythmic events, hyperkalaemia) Change in NYHA class Change in management HF medication use HF advanced therapy use, including disease specific therapies Repeat testing or additional testing Additional revascularisation events Patient and carer satisfaction Successful administration of intervention Withdrawal due to adverse events/tolerability Medicine optimisation and adherence Dying in preferred place of death (for palliative care patients) Adherence to intervention Health service use The absolute risk difference was also calculated using GRADEpro138 software, using the median event rate in the control arm of the pooled results. For binary variables where there were zero events in either arm or a less than 1% event rate, Peto odds ratios, rather than risk ratios, were calculated. Peto odds ratios are more appropriate for data with a low number of events. Continuous outcomes Continuous outcomes were analysed using an inverse variance method for pooling weighted mean differences.


Continuous outcomes Continuous outcomes were analysed using an inverse variance method for pooling weighted mean differences. These outcomes included: heath-related quality of life (HRQoL) Time to death Change in exercise capacity Improvement in exercise tolerance Change in haemoglobin in anaemic patients Improvement in ejection fraction Change in dyspnoea Weight change or change in oedema Change in sodium level Where the studies within a single meta-analysis had different scales of measurement, standardised mean differences were used (providing all studies reported either change from baseline or final values rather than a mixture of both); each different measure in each study was normalised to the Chronic Heart Failure Methods NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: 978-1-4731-3093-7 standard deviation value pooled between the intervention and comparator groups in that same study. The means and standard deviations of continuous outcomes are required for meta-analysis. However, in cases where standard deviations were not reported, the standard error was calculated if the p values or 95% confidence intervals (95% CI) were reported, and meta-analysis was undertaken with the mean and standard error using the generic inverse variance method in Cochrane Review software. Where p values were reported as less than , a conservative approach was undertaken. For example, if a p value was reported as p 0.001 , the calculations for standard deviations were based on a p value of 0.001. If these statistical measures were not available then the methods described in section 16.1.3 of the Cochrane Handbook (version 5.1.0, updated March 2011) were applied.