Update on management of chronic heart failure

Consultant Cardiologist,

South Yorkshire Cardiothoracic Centre,

Sheffield Teaching Hospitals NHS 

Foundation Trust, Sheffield, UK

Professor of Primary Care Research,

General Practice and Primary Care Research Unit, University of Cambridge, UK

Chronic heart failure (CHF) is a major healthcare concern.(1) The incidence of CHF is not rising; however, prevalence is increasing due to better survival rates of conditions that could lead to heart failure such as ischaemic heart disease and hypertension and due to the ageing population.(2,3) Patients with CHF experience breathlessness, fatigue and fluid retention. In addition, CHF results in high hospitalisation and mortality rates, carrying a substantial economic burden. The National Institute for Health and Clinical Excellence (NICE) for England and Wales updated its original 2003 heart failure guidelines in 2010.(4,5)

Figure 1 shows the diagnosis algorithm for CHF. The primary care physician obtains a detailed history, conducts a physical examination and undertakes ancillary tests. If a patient is suspected of having heart failure and does not have a history of myocardial infarction, the primary care physician should measure serum natriuretic peptides. If serum natriuretic peptides are elevated or if the patient had a previous myocardial infarction, the patient should be referred for echocardiography and a clinical evaluation by a specialist.(5) The basis for not recommending measurement of natriuretic peptides in patients suspected of having heart failure with previous myocardial infarction is cost-effectiveness analyses. A patient with symptoms of heart failure and with a history of myocardial infarction is significantly more likely to be in heart failure than someone who has the same symptoms but no history of myocardial infarction.(6)

The specialist establishes the diagnosis and assesses the severity and potential causes of heart failure. Echocardiography is useful in confirming the diagnosis, in assessing valve disease, systolic and diastolic ventricular functions and in detecting intra-cardiac shunts.(4)

Heart failure is associated with poor quality of life, high hospitalisation rate and high mortality rate. Pharmacological and device therapies improve these outcomes. The chance of a poor outcome is highest early after the onset of the syndrome.(7) Hence, it is imperative to promptly establish the diagnosis and commence therapy. NICE advises that echocardiography and specialist evaluation occur within two weeks of the presentation in those with the highest risk (history of myocardial infarction or high natriuretic peptide levels) and no later than 6 weeks from the presentation if the natriuretic peptides are not high but raised.

Clinical signs and symptoms of heart failure are important but not always diagnostic. Serum natriuretic peptides (B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) have high sensitivity for diagnosis of heart failure. Serum natriuretic peptides are useful to identify people who are unlikely to have heart failure (because of lower natriuretic peptide levels) and therefore do not need specialist referral. The cut-off thresholds for natriuretic peptides used by NICE were consistent with cut off levels proposed in an economic analysis appraised for the guideline(7) and the same as those based on consensus and recommended by the European Society of Cardiology.(8)

NICE defined the specialist as a physician with sub-specialty interest in heart failure (often a consultant cardiologist) who leads a specialist heart failure multi-disciplinary team (HF-MDT). The HF-MDT is composed of professionals with appropriate competencies from primary and secondary care and may involve, where necessary, other services (rehabilitation, tertiary care, palliative care) in the care of individual patients.

Before choosing therapy, patients with heart failure should be classified based on the echocardiographic findings into those with heart failure due to left ventricular systolic dysfunction (HF-LVSD) and those whose left ventricular ejection fraction is preserved (HFPEF) (Figure 2).

There are two recommendations for these patients:

use diuretics for the relief of congestion and oedema

treatment of co-morbidity such as hypertension, ischaemic heart disease and diabetes mellitus.

None of the few studies of specific therapies in patients with HFPEF provide sufficient evidence to recommend their routine use.

The pharmacological therapy of patients with HF-LVSD was divided into first and second line therapy by NICE.

There is strong evidence supporting the use of first line therapy as a combination of angiotensin-converting enzyme inhibitors (ACEIs) and a beta-blocker of proven effectiveness in heart failure (bisoprolol, carvedilol, metoprolol succinate, nebivolol).(9,10) ACEIs and beta-blockers reduce morbidity and increase survival of patients with HF-LVSD.(9,11) Beta-blockers reduce morbidity and mortality of patients with HF-LVSD, including older adults (age ≥65).(12) There is no difference in the outcome whether an ACEI or a beta-blocker is started first.(13) Beta-blockers should be given to all patients with heart failure due to HF-LSVD including older adults and patients with peripheral vascular disease, erectile dysfunction, diabetes mellitus, interstitial pulmonary disease and chronic obstructive pulmonary disease without reversibility. If a patient develops heart failure while on treatment for a co-morbidity, the beta-blocker should be switched to one of the four agents mentioned above.

If ACEIs are not tolerated, angiotensin receptor blockers (ARBs) effective in heart failure (especially candesartan and valsartan) are an alternative.(14) However, since there is better evidence for ACEIs than ARBs, it is recommended that switching ACEIs to ARBs be limited to when the side-effects are intolerable.

Patients unable to receive ACEIs or ARBs (due to angio-oedema or advanced chronic kidney disease without renal replacement therapy) could be treated with hydralazine and nitrate combination.(15)

Patients whose symptoms persist despite optimising their first line-therapy should be considered by a specialist for the most appropriate second-line pharmacological therapy. The second line is one of three agents: an aldosterone antagonist (AA), an ARB or a combination of hydralazine and nitrates.

The addition of an AA in patients with HF-LVSD results in significant reductions of both morbidity and mortality.(16) NICE recommended AA use in patients with moderate to severe symptoms. However, since the guidelines were published in 2010, the EMPHASIS-HF (Eplerenone in Mild Patients Hospitalisation and Survival Study in Heart Failure) trial showed the effectiveness of eplerenone in the treatment of HF-LVSD with mild symptoms.(17)

Patients receiving AA in addition to either ACEIs or ARBs should be closely monitored for any deterioration of renal function or hyperkalaemia. The monitoring of renal profile should be done at 1, 4, 8 and 12 weeks and then every three months.

Beyond its place in some cases as a first line therapy, hydralazine and nitrate combination lowers mortality in patients with HF-LVSD. It is a valuable addition to therapy in patients of Afro-Caribbean origin.(18)

Angiotensin receptor blockers reduce admissions for heart failure and improve quality of life but do not have a significant effect on survival.(14,19,20) It is important to monitor the patient when on both ACEIs and ARBs for the risks of hyperkalaemia and raised serum creatinine.(20) The combination of ARBs with both ACEIs and beta-blockers in patients with HF-LVSD can reduce the composite outcome of cardiovascular mortality and heart failure hospitalisation.(21)

The specialist’s initial assessment at the time of diagnosis considers the indications for implantation of a cardioverter defibrillator (ICD) irrespective of the severity of the symptoms.(22) Indications include sustained ventricular tachycardia or non-sustained ventricular tachycardia which is inducible on electro-physiological testing if the left ventricular ejection fraction (LVEF) is <35% or a QRS duration ≥120ms if the LVEF is <30%.  

Where the patient continues to be symptomatic despite optimal first and second line therapy, the specialist’s opinion should be sought to consider the appropriateness of other drugs and the use of cardiac resynchronisation therapy (CRT).(23) The criteria for CRT in these circumstances include LVEF <35% and QRS duration ≥150ms or between 120 and 149ms in the presence of mechanical dyssynchrony on echocardiography.

The pharmacological interventions at this late stage include adjustment to diuretic therapy and the introduction of digoxin.(5) However, since the NICE guidelines were published in 2010 the SHIFT (Systolic Heart Failure Treatment with /f Inhibitor Ivabradine Trial) study was published and suggested the addition of ivabradine could significantly reduce hospitalisation risk and improve survival in patients with HF-LVSD who are still in sinus rhythm with a heart rate of  >70.(24)

Rehabilitation of patients with heart failure can lead to reduced heart failure hospitalisation and improved quality of life. Thus, NICE recommends supervised group exercise-based heart failure rehabilitation programmes to all patients with heart failure. These programmes should include psychological and educational components. 

Heart failure is characterised by a progressive and an unpredictable clinical course. Monitoring aims to optimise therapy, reduce hospitalisation and minimise complications.(4) In addition, NICE recommends that specialist monitoring of serum natriuretic peptides should be considered in some patients to aid uptitration of pharmacological therapy and in patients with repeated hospitalisation.(5) Use of serum natriuretic peptide monitoring to guide therapy could reduce hospitalisation. There is also evidence that natriuretic peptide guided therapy reduces mortality in people under the age of 75.

It is not clear from the trials of telemonitoring whether the observed benefits were due to telemonitoring or to the improved access to care associated with it. Since the NICE guidelines were published, a large trial of telemonitoring for patients with a recent admission for heart failure found no evidence that this reduced re-admission or mortality rates.(25)

Since the publication of the NICE guidelines on CHF (partial update) in 2010, several clinical trials were published on topics that may or may not have affected some of the guidelines recommendations. Three of these trials are mentioned above.(17,24,25)

The RAFT (Resynchronisation/Defibrillation for Ambulatory Heart Failure Trial) trial reported that the addition of CRT to an ICD in people with mild to moderate heart failure led to a reduction in all cause mortality and hospitalisation but at the cost of increased adverse events.(26) 

The partial update of the CHF NICE guidelines created changes to the way the diagnosis of heart failure is made and to the management and monitoring of these patients. In diagnosis, the guidelines give prominence to a history of myocardial infarction and a rise in natriuretic peptides to guide entry to the diagnostic pathway which includes echocardiography and a specialist’s assessment in a time-sensitive manner. In treatment, the guidelines put beta blockers with ACEIs as first line therapy for HF-LVSD, offer options for second line therapy (AA, ARBs or combined nitrates and hydralazine) and recommend that all patients with heart failure whose symptoms are stable and without definite contra-indication should be offered a group exercise based rehabilitation programme. The guidelines did not recommend any specific therapy for HFPEF beyond diuretics and did not recommend telemonitoring.

The proposed access to cardiological investigations by NICE differed from the European guidelines on the basis of cost-effectiveness analyses.(8) Despite the expected increase of expenditure on the diagnosis of heart failure and perhaps on increased uptake of therapeutics, it is anticipated that this 

will be offset by improved heart failure outcomes, especially reduction of hospitalisation rates.(27) 

1. Cowie MR et al. Incidence and aetiology of heart failure: a population-based study. Eur Heart J 1999;20:421–28.
2. Owan TE et al. Trends in prevalence and outcome of heart failure with preserved ejection fraction. New Engl J Med 2006;355:251–59.
3. McKee PA et al. The natural history of congestive heart failure. N Engl J Med 1971;285(26):1441–6.
4. National Institute for Health and Clinical Excellence (NICE). Chronic heart failure (clinical guideline 5). London: Royal College of Physicians, 2003.
5. NICE. Chronic heart failure: management of chronic heart failure in adults in primary and secondary care (clinical guideline 108). London: NICE; 2010.
6. Mant J et al. Systematic review and individual patient data meta-analysis of diagnosis of heart failure, with modelling of implications of different diagnostic strategies in primary care. Health Technology Assessment 2009; 13; doi: 10.3310/HTA 13320.
7. Kubanek M et al. The prognostic value of repeated measurement of N-terminal pro-B-type natriuretic peptide in patients with chronic heart failure due to left ventricular systolic dysfunction. Eur J Heart Fail 2009;11(4):367–77.
8. Dickstein K al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008. Eur Heart J 2008;29:2388–442.
9. Flather MD et al. Long-term ACE-inhibitor therapy in patients with heart failure or left-ventricular dysfunction: a systematic overview of data from individual patients. ACE-Inhibitor Myocardial Infarction Collaborative Group. Lancet 2000;355:1575–81.
10. Packer M et al. Effect of carvedilol on the morbidity of patients with severe chronic heart failure: results of the Carvedilol Prospective Randomised Cumulative Survival (COPERNICUS) study. Circulation 2002;106:2194–99.
11. Shibata MC, Flather MD, Wang D. Systematic review of the impact of beta blockers on mortality and hospital admissions in heart failure. Eur J Heart Fail 2001;3:351–57.
12. Flather MD et al. Randomised trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure (SENIORS). Eur Heart J 2005;26(3):215–25.
13. Willenheimer R et al. Effect on survival and hospitalisation of initiating treatment for chronic heart failure with bisoprolol followed by enalapril as compared with the opposite sequence: results of the randomised Cardiac Insufficiency Bisoprolol Study (CIBIS) III. Circulation 2005;112(16):2426–35.
14. Granger CB al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial. Lancet 2003;362(9386):772–76.
15. Cohn JN et al. Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of a Veterans Administration Cooperative Study. N Engl J Med 1986;314:1547–52.
16. Pitt B et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomised Aldactone Evaluation Study Investigators. N Engl J Med 1999;341(10):709–17. 
17. Zannad F et al. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med 2011;364:11–21.
18. Taylor AL et al. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med 2004;351(20):2049–57.
19. Krum H et al. Effect of valsartan added to background ACE inhibitor therapy in patients with heart failure: results from Val-Heft. Eur Heart J 2004;6(7):937–45.
20. Houghton AR et al. Combined treatment with losartan and an ACE inhibitor in mild to moderate heart failure: results of a double-blind, randomised, placebo-controlled trial. Am Heart J 2000;140(5):e25–e31.
21. McMurray JJ et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial. Lancet 2003;362(9386):767–71.
22. NICE. Implantable cardioverter defibrillators for arrhythmias (technology appraisal guidance 95). London: NICE; 2006.
23. NICE. Cardiac resynchronisation therapy for the treatment of heart failure (technology appraisal guidance 120). London: NICE; 2007.
24. Swedberg K et al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet 2010;376:875–85.
25. Chaudhry SI et al. Telemonitoring in patients with heart failure. N Engl J Med 2010;363:2301–09.
26. Tang ASL et al. Cardiac resynchronisation therapy for mild to moderate heart failure. N Engl J Med 2010;363:2385-95.
27. NICE. Chronic Heart Failure: Costing Report. Implementing NICE Guidance. (CG 108). London: NICE 2010.