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Heart failure: recent advances in diagnosis and managementDrug review Heart failure Heart failure: recent advances in diagnosis and management
Russell Davis MD, FRCP
Our Drug review highlights the significant advances that have been seen in the diagnosis and treatment of heart failure in recent years, followed by sources of Heart failure is a common condition, affecting up gation of cardiac function, although other imaging to 3 per cent of the population aged 45 and older, including nuclear medicine gated blood pool studies and is associated with high mortality and poor quality (multi-gated acquisition scan – MUGA), cardiac of life. Major diagnostic and therapeutic advances have magnetic resonance imaging (MRI) and contrast been made over the past three decades, but interna- angiography may be useful, especially where tional and national audits suggest that many patients echocardiographic image quality is poor. are incompletely investigated and treated. This article will review some key points and recent Low BNP makes heart failure diagnosis developments in the diagnosis and treatment of heart unlikely Heart failure in ambulant patients is an unlikely diag- nosis in those with low serum natriuretic peptide levels Diagnosis of heart failure depends on (B-type natriuretic peptide – BNP <100pg per ml or both symptoms and objective evidence N-terminal pro-BNP – NTproBNP <400pg per ml), of cardiac dysfunction and the recent National Institute for Health and CPD questions
Clinical features and chest radiography are not suf- Clinical Excellence (NICE) guideline1 recommends available for
ficient to make a diagnosis of heart failure! that one of these peptides be assayed in all patients this article.
Echocardiography is normally the preferred investi- presenting with suspected heart failure in primary See page 25
Prescriber July 2012 tant angina with symptoms uncontrolled on full med- Ivabradine recently licensed for use inheart failureBased on the results of the SHIFT study (see Figure 3),5 ivabradine (Procoralan) was recently approved for use in patients with heart failure NYHA class II–IV and left ventricular systolic dysfunction (ejection fraction <35 per cent) whose resting heart rate was over 75 beats per minute, whether treated with a beta-blocker or not.
Ninety per cent of patients in the SHIFT study were on beta-blockers, where interestingly the heart rate had to be only >70 to qualify. The greatest benefit was seen in those with higher heart rates. Figure 1. Echocardiography is the preferred investigation
In clinical practice it may be possible to uptitrate care. Those with low levels will not require further the dose of beta-blocker to get the heart rate <75 in referral for echocardiography. As the natriuretic pep- many cases,6 but there are still many patients where tide levels also predict prognosis, those with very high this is not possible due to hypotension and other intol- levels need urgent assessment (within two weeks). erance, and the use of ivabradine is a significant Due to costs, despite the NICE guideline, natri- advance especially for those patients where beta-block- uretic peptide testing is not available in all areas at ers are genuinely contraindicated.
present. It can, however, be very useful in patient care and, with the mandate of NICE guidelines, should be Beta-blockers can be used in patients arranged in all areas as a priority. The diagnosis flowchart from the NICE guideline Despite popular belief, beta-blockers have been used (see Figure 2) shows the recommended place of natri- safely and successfully in heart failure patients with uretic peptide testing. proven COPD with no reversibility of airflow obstruc- tion on spirometry, and the recently updated NICE Importance of aetiology guideline recommends their use in this situation. A Heart failure is a syndrome that can arise as a result of cardioselective agent such as bisoprolol or nebivolol many diverse forms of heart disease, including coro- (Nebilet) may be preferable to the less selective nary artery disease, hypertension, valvular disease, con- carvedilol in this situation. genital disease, viral heart disease (myocarditis), etc.
Lung function laboratories may be more likely to Therefore, a full diagnosis will require establishment carry out reversibility testing if it is stated on the request of which disease process led to the heart failure. that testing is mandated by NICE for this indication! Routine invasive coronary angiography is not always needed, however, especially where coronary revascu- Heart failure with preserved ejection larisation is not being considered. Rather surprisingly, ‘standard' treatments for Patients with heart failure with preserved ejection ischaemic heart disease (IHD) such as statins fraction (HFPEF) can be a heterogeneous group.
(CORONA study)2 and aspirin3 are not of proven Despite repeated studies showing that patients value in heart failure even when caused by IHD, and admitted with HFPEF have a poor prognosis, often the STICH study,4 likely to be the largest of its kind, as poor as that for patients with systolic dysfunction, of surgical revascularisation of patients with IHD failed there is still no definite evidence on how to treat to meet its primary end-point of reduction of all-cause HFPEF as yet. mortality, although some secondary end-points were Diuretics should be used for symptomatic benefit and it is sensible to manage any underlying cause if pos- In light of these findings, noninvasive assessment sible, eg hypertension with left ventricular hypertrophy. of aetiology, eg with MRI and nuclear medical tech- The results of the large Treatment of Preserved niques, may be preferable in many cases. Cardiac Function Heart Failure with an Aldosterone Cardiac surgery remains invaluable in heart fail- Antagonist (TOPCAT) study of spironolactone are ure due to valve disease and where there is concomi- keenly awaited.7 Prescriber July 2012 Use of mineralocorticoid receptor antagonists will benefit many patientsSpironolactone and eplerenone (Inspra) have been established treatments for severe chronic heart failure8 and for postinfarct heart failure9 for several years.
More recently, the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF) study has shown great benefit of eplerenone in milder (NYHA Class II) heart failure patients who had left ventricular ejection fraction of <35 per cent, which significantly widens the indication for mineralocorticoid receptor antagonists (MRAs).10 Overall mortality, as well as hospitalisation for heart failure, was significantly reduced in the eplerenone arm (see Figure 5). While this will lead to prognostic benefits for many patients, and in the study the incidence of significant adverse events including hyperkalaemia was relatively low, the ‘real-world' incidence of side-effects from MRAs is considerable11 and careful monitoring will be needed. It is important to note that trial participants had to have a serum potassium level of <5.0mmol per litre and an estimated glomerular filtration rate (eGFR) of more than 30ml per minute per 1.73m2 body surface area. Specialist nursing and/or pharmacy teams may be ideally placed to carry forward the patient moni- toring on treatment.
Deterioration of previously stablepatients on treatment should prompt adetailed review including a fresh ECGPatients who are on treatment for heart failure who have been stable on evidence-based treatments can nevertheless deteriorate either acutely or gradually.
While this may be due to progression of underlying disease that may not be treatable, there is often a pre- cipitant that may be amenable to medical treatment.
A careful and comprehensive review should be car- A full blood count may show anaemia that may be due to gastrointestinal bleeding – particularly com- mon in heart failure patients with poor intestinal per- fusion who are taking antithrombotic medication.
Urea and electrolytes may show deterioration of renal function. Thyroid function tests may become abnor- mal, especially in patients taking amiodarone. An ECG may show new-onset atrial fibrillation that may be amenable to cardioversion and in most heart failure patients is a strong indication for anticoagula- tion. The ECG may also show evidence of a new ischaemic event or MI, and new conduction abnormal- ities such as high-degree heart block and new left bun- dle branch block – now highly treatable with cardiac Prescriber July 2012 take detailed history and perform clinical examination natriuretic peptides specialist assessment abnormality consistent no clear abnormality consider measuring with heart failure serum natriuretic peptides if levels assess severity, aetiology, precipitating factors, type of cardiac dysfunction, correctable causes investigate other heart failure due to left heart failure with pres - heart failure unlikely, ventricular systolic erved ejection fraction Serum natriuretic peptides
high levels – BNP >400pg/ml (116pmol/litre) or NTproBNP >2000pg/ml (236pmol/litre) raised levels – BNP 100–400pg/ml (29–116pmol/litre) or NTproBNP 400–2000pg/ml (47–23pmol/litre) normal levels – BNP <100pg/ml (29pmol/litre) or NTproBNP <400pg/ml (47pmol/litre) Figure 2. Heart failure diagnosis flowchart from the NICE guideline, 2010; after reference 1
Prescriber July 2012 established diagnosis and who are on evidence-based treatments may be able to be avoided.
placebo (937 events)ivabradine (793 events) Diabetic management may need HR 0.82 (95% Cl 0.75–0.90), p<0.0001 Although less marked than with the now-withdrawn rosiglitazone, pioglitazone13 is also associated with an increased heart failure risk and with fluid retention, and heart failure is now listed as a contraindication to pioglitazone use. With its lower propensity to cause weigh gain than other hypoglycaemic medication, many patients with heart failure are usefully treated with metformin.
However, particularly vigilant monitoring of renal func- tion is recommended for those on diuretics and other medication for heart failure. NICE recommends that metformin dosage should be reviewed if eGFR falls below Figure 3. Incidence of primary end-point (composite of cardiovascular death or hos-
45ml per minute per 1.73m2, and metformin avoided if pital admission for worsening heart failure), ivabradine vs placebo; after reference 5 eGFR falls below 30 due to the risk of lactic acidosis.14 resynchronisation therapy (CRT – see Figure 6) or Exercise and rehabilitation biventricular pacing.12 Although the largest study (Heart Failure: A In terms of development of services in the future, Controlled Trial Investigating Outcomes of Exercise rapid availability of such comprehensive reassessment Training – HF-ACTION)15 showed only small reduc- of patients who become unstable should be a priority. tions in the primary end-points of mortality and hos- Meanwhile, ‘routine' reviews of patients who have an pitalisation, this and other studies have shown benefits in quality of life and rehabilitation is a key recommen- evidence that intravenous furosemide can be safely dation in the NICE heart failure guideline.
given to ambulatory heart failure patients at a day unit,16 with considerable potential cost savings. This is Selected patients may be able to receive obviously more applicable to those with worsening intravenous diuretics without hospital chronic fluid overload than those with acute pulmonary oedema. Work is also ongoing to study the use of intra- With increasing pressure on hospital beds and patients venous diuretics by specialist nurses in patients' homes.
preferring to be treated out of hospital, there is recent continued on page 24 heart failure with heart failure due preserved ejection to left ventricular systolic dysfunction manage co-morbid conditions offer both ACE inhibitors and such as high blood pressure, beta-blockers licensed for heart angiotensin-II receptor ischaemic heart disease and failure as first-line treatment blocker (ARB) if intoler- diabetes mel itus in line with ant of ACE inhibitors specialist assessment consider hydralazine in combination with nitrate if intolerant of ACE inhibitors if symptoms persist despite optimal first-line treatment, seek specialist advice and for second-line treatment consider adding: • an aldosterone antagonist licensed for heart failure offer rehabilitation (especial y in moderate to severe heart failure or MI and education, and implantable cardio - in past month) or diuretics for congestion vascular defibril ator • an ARB licensed for heart failure (especial y in mild and fluid retention where appropriate to moderate heart failure) or • hydralazine in combination with nitrate (especial y in people of African or Caribbean origin with mod-erate to severe heart failure) if symptoms persist consider:• cardiac resynchronisation therapy (pacing with or without a defibril ator) Figure 4. Recommended management of heart failure from the NICE guideline, 2010; after reference 1
Prescriber July 2012 distressing to both patients and their relatives.
However, bradycardia packing and CRT functions would normally be left activated on a device. Many of the principles of end-of-life care in heart HR 0.76 (95% Cl 0.62–0.93), p=0.008 failure are common to those in other terminal illnesses, and fortunately access to specialist palliative care is improving in many areas for heart failure patients.
ConclusionThe treatment of heart failure has evolved rapidly over the past few years and many aspects of this are consid- ered in this article. Patients are often complex, with multiple co-morbidities, and being under specialist care has been shown to be associated with greater use of evidence-based therapies and improved survival.
Years since randomisation Figure 5. Principal results from the EMPHASIS study, eplerenone vs placebo; after
1. NICE. Chronic heart failure: The management of adults with chronic heart failure in primary and secondary care (partial update).
Clinical guideline 108. 2010. www.nice.org.uk/CG108.
Priorities change as end of life 2. Kjekshus J, et al; CORONA Group. N Engl J Med 2007; Symptom control and avoidance of hospital admissions, 3. Cleland JG, et al. Am Heart J 2004;148:157–64. which many patients find distressing, take precedence 4. Velazquez EJ, et al; STICH Investigators. N Engl J Med over prognostic issues in patients who are irrevocably 2011;364:1607–16. 5. Swedberg K, et al; SHIFT Investigators. Lancet 2010;376: approaching the end of life. Many patients may be able 875–85.
to stop ‘prognostic' medications such as statins and mul- 6. Cullington D, et al. Heart 2011;97:1961–6.
tiple antiplatelet and antithrombotic agents. Subcut - 7. Desai AS, et al. Am Heart J 2011;162:966–72.
aneous furosemide can have a role in selected patients.17 8. Pitt B, et al. N Engl J Med 1999;341:709–17.
Implantable cardioverter-defibrillators (ICDs) 9. Pitt B, et al; Eplerenone Post-Acute Myocardial Infarction should be deactivated in those who are in the late Heart Failure Efficacy and Survival Study Investigators. N stages of terminal decline due to heart failure, as Engl J Med 2003;348:1309–21. attempted defibrillations will be likely to be futile and 10. Zannad F, et al; EMPHASIS-HF Study Group. N Engl J Med 2011;364:11–21. 11. Svensson M, et al. BMJ 2003;327:1141–2.
12. Cleland JG, et al; Cardiac Resynchronization-Heart Failure (CARE-HF) Study Investigators. N Engl J Med 2005; 352:1539–49.
13. Hernandez AV, et al. Am J Cardiovasc Drugs 2011;11:115–28.
14. NICE. Type 2 diabetes: The management of type 2 diabetes.
Clinical guideline 87. 2009.
15. O'Connor CM, et al. JAMA 2009;301:1439–50.
16. Banerjee P, et al. Clinical Medicine 2012;12:133–6.
atients free of d 17. Zacharias H, et al. Palliat Med 2011;25:658–63.
Declaration of interests Dr Davis has received honoraria from Servier and Pfizer, and has received research funding into heart failure from the British Heart Foundation and the National Institute for Health Research.
Dr Davis is consultant cardiologist and honorary senior Figure 6. Main results of CARE-HF study showing mortality benefits of cardiac
lecturer, Sandwell & West Birmingham Hospitals NHS resynchronisation therapy in addition to optimised medical therapy Trust, West Bromwich Prescriber July 2012 ResourcesFurther reading British Society for Heart Failure. Tel: 01865 391836, 1. NICE. Chronic heart failure: The management of adults website: www.bsh.org.uk. Aims to increase knowledgewith chronic heart failure in primary and secondary care and promote research about the diagnosis and man-(partial update). Clinical guideline 108. 2010. agement heart failure.
Patient information Groups and organisations Medicine guide on heart failure. Information for British Heart Foundation. Tel: 020 7554 0000, website: patients on drugs used in heart failure.
www.bhf.org.uk. Produces books, pamphlets, videos, http://medguides.medicines.org.uk/document.aspx? posters and factsheets.
CPD: Management of heart failure
Answer these questions online at Prescriber.co.uk and receive a certificate of completion for your CPD portfolio. Utilise the Learning into Practice form to record how your learning has contributed to your professional development.
1. One of these statements about heart failure is false –
4. Which one of these statements about treatments for heart
which is it?
failure is false?
a. It affects up to 3 per cent of the population aged ≥45 a. Ivabradine is licensed for use in patients whose resting b. Audits show that many patients are incompletely investi- heart rate is over 85 beats per minute gated and treated b. In the SHIFT study, the greatest benefit of treatment with c. Clinical features and chest radiography are not sufficient to ivabradine was seen in those with higher heart rates make a diagnosis of heart failure c. Ivabradine is a significant advance for patients unable to d. Cardiac MRI is the preferred investigation of cardiac func- take a beta-blocker due to contraindications d. Nebivolol is more cardioselective than carvedilol 5. Which one of these statements is false?
2. Which one of these statements is false?
a. There is insufficient evidence to define the optimal treatment a. Low serum natriuretic peptide levels confirm the diagnosis of patients with heart failure with preserved ejection fraction of heart failure in ambulant patients b. New-onset atrial fibril ation is a strong indication for anti - b. NICE recommends that one of the serum natriuretic pep- coagulation in most heart failure patients tides should be assayed in al patients presenting with sus- c. Metformin is an appropriate oral antidiabetic agent for pected heart failure in primary care many patients with heart failure provided their eGFR c. Natriuretic peptide levels predict prognosis remains above 20ml per minute per 1.73m2 d. Noninvasive assessment of aetiology, such as MRI and d. High-degree heart block and new left bundle branch block nuclear medical techniques, are preferred to invasive coro- can be treated with cardiac resynchronisation therapy or nary angiography for many patients biventricular pacing 6. Which one of these statements about the management of
3. One of these statements is false – which?
patients with heart failure is false?
a. Heart failure is a syndrome a. Exercise achieves a smal reduction in hospitalisation rates b. The CORONA study showed that statins or aspirin improve in patients with heart failure heart failure symptoms in patients with ischaemic heart dis- b. Symptom control and avoidance of hospital admissions take precedence over prognostic issues in patients who are c. The STICH study showed that surgical revascularisation of irrevocably approaching the end of life patients with ischaemic heart disease failed to reduce al - c. Implantable cardioverter-defibril ators should be deactivat- ed in patients in the late stages of terminal decline due to d. Cardiac surgery is invaluable in patients with heart failure heart failure, but bradycardia packing and CRT functions due to valve disease and angina when symptoms are should normal y be left activated uncontrol ed on ful medical therapy d. Iv furosemide can only safely be administered to inpatients Prescriber July 2012
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