The ESC's updated heart failure guidelines are timely and authoritative and should help promote evidence-based practice, says Dr Andrew Clark

Chronic heart failure (CHF) is the most common cause of medical admission to hospital in the UK. Around 1% of the population suffer from the condition, which affects predominantly older people: nearly 90% of incident cases are over 65 years of age, and 50% are over 80.1

Heart failure is a malignant disease. Not only is it the cause of severe morbidity and recurrent hospital admissions, but it also has a high mortality. Five-year survival is only 25% for men.2

Since the publication of the first CONSENSUS study in 1987,3 a number of clinical trials have demonstrated that a variety of treatments have the potential to reduce morbidity and mortality.

Despite this wealth of data, we do not treat patients as well as we might. For example, only around 60% of patients across Europe are receiving an angiotensin-converting enzyme (ACE) inhibitor.4 More recently introduced therapy, particularly beta-blockers, are even less widely prescribed across Europe. For example, only 7% of patients in Portugal with heart failure receive beta-blockers.5

Guidelines have a potential role to play in encouraging better management of this common condition. The Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology (ESC) has recently published its updated guidelines.6 These guidelines are a development of early work published in 1995 and 1997.7, 8 Much has happened in the intervening years, and the revised guidelines are timely, authoritative and comprehensive.

To be effective, of course, the guidelines need to be widely disseminated and widely read. Since much of heart failure management takes place in primary care, a mechanism for reaching beyond the natural readership of the European Heart Journal is needed.

The guidelines take the reader from epidemiology of heart failure through to a discussion of the organisation of care. The writing committee has managed to maintain a pretty firm grip on the structure of the document, and so it is lucid and at the same time to the point.

Where evidence for a particular treatment exists, the evidence is presented and highlighted. Where no such evidence exists, the guidelines do not shy away from saying so.

Definition of heart failure

Despite the huge body of heart failure research, the definition still arouses controversy. The present guidelines opt for the pragmatic definition of requiring symptoms compatible with heart failure in the presence of objective evidence of cardiac dysfunction. In some cases, a beneficial response to treatment might be necessary to complete the diagnosis.

As a definition, this is imprecise. Many individuals have symptoms suggestive of heart failure, but apparently normal hearts. Again, many asymptomatic individuals apparently have left ventricular function below normal (inevitably as cardiac function is near-normally distributed). There is a substantial grey area where the two overlap – should a breathless person with an ejection fraction of 50% be considered normal, whereas one with an ejection fraction of 49% has heart failure?

In future it may become easier to distinguish individuals with and without heart failure on the basis of blood tests. Natriuretic peptides are released in response to cardiac stretch, and are raised in untreated heart failure. The B-type natriuretic peptide (BNP) seems to be the most helpful.9

It has not yet found its place in clinical practice, but it may prove to be the case that we should treat those with a raised BNP. Those with a reduced ejection fraction but normal BNP may simply represent the end of the normal range.

It is important to recognise that the majority of the guidelines (and, indeed, the majority of the evidence) relates to patients with heart failure due to systolic left ventricular dysfunction. Much less is known about so-called diastolic heart failure (see below).

Investigations

The key investigation in establishing a diagnosis of heart failure is some form of cardiac imaging. The ESC guidelines strongly favour echocardiography. It is becoming more widely available, and is quick and non-invasive. As well as information about global left ventricular systolic function, it gives information on valve function, regional cardiac function and diastolic function.

An important additional investigation is stress echocardiography, which may be a way of identifying which patients might benefit from revascularisation.

Heart failure is not of itself a sufficient diagnosis. The cause of the heart failure syndrome should be sought in each patient. Although coronary artery disease is the most common cause, occasional patients have a treatable underlying cause which should not be missed.

Treatment of heart failure

The standard description of the management of heart failure normally pays lip service to non-pharmacological management. In particular, education of the patient and carer can have a major beneficial effect in helping patients come to terms with their condition and in reducing hospitalisations.

This need not be particularly onerous: a single home visit can have striking beneficial effects.10 Typical advice is that patients should avoid exercise and try to lose weight. As with much advice that used to be given to patients, neither of these statements is based on any evidence.

The ESC guidelines point out that there is much evidence that exercise may be beneficial.11 More controversially, the effects of weight loss have never been demonstrated. Cardiac cachexia is a strongly adverse prognostic feature,12 and some recent work has suggested that mild obesity may, in fact, be beneficial.

Management should include advice, education and support. The role of the heart failure nurse specialist is increasingly being recognised as particularly important in helping patients learn about their condition, manage their therapy and thereby reduce hospital admissions, and perhaps improve outcome.

Pharmacological treatment

The evidence base for heart failure management is large and there is firm evidence for the mortality benefit of several of our treatments.

However, much of the trial work has been conducted with mortality as the primary end-point. This has the merit of being an easily understood and easily defined end-point, and gives firm guidance for drug use. It does mean, however, that we have a less firm knowledge base of treatment for symptomatic benefit. The drug treatment of heart failure is summarised in Table 1 (below).

Table 1: Summary of drug treatment of heart failure

NYHA

Diuretic Beta-blocker ACEi Digoxin Spironolactone
I for fluid retention + +    
II for fluid retention + +    
III for fluid retention + + + +
IV for fluid retention + + + +
ACEi = angiotensin-converting enzyme inhibitor
NYHA is symptomatic class of heart failure:
I, no symptoms
II, symptoms on moderate exertion
III, symptoms on mild exertion
IV, symptoms at rest

Diuretics

Loop diuretics are almost universally prescribed in heart failure. While the occasional patient might get by with a thiazide, this is uncommon. The combination of loop + thiazide is particularly potent, but needs to be managed carefully, with particular regard to the risk of dehydration.

Spironolactone is a diuretic that conveys a mortality benefit to patients with severe heart failure (NYHA class 3 and 4), as shown in the RALES trial.13 It is thought to work predominantly as an aldosterone antagonist rather than a diuretic.

It is important to note that low dose spironolactone was used in the trial (12.5-50mg once daily), and that it has been shown to work only in severely affected patients.

There is a widespread perception that spironolactone is safe, and it is widely used in more mildly affected patients. There is a danger of severe hyperkalaemia, especially when the patients are also treated (as they should be) with an ACE inhibitor. Potassium should be closely monitored.

ACE inhibitors

ACE inhibitors are well known to be beneficial in all grades of heart failure, and there is little new to recommend. It is important to emphasise that simply starting an ACE inhibitor is not enough: the dose should be titrated up to that shown to be effective in clinical trials. My personal view is that only those drugs shown to be effective should be used.

The issue of angiotensin-receptor blockers (ARBs) is touched upon in the guidelines. There is no evidence to suggest that they are superior to ACE inhibitors, yet there is a vogue for using them at the slightest suggestion of ACE inhibitor side-effects. It is probably the case that an ARB is better than nothing, but I would prefer to be on an ACE inhibitor.

Combination therapy is also controversial. There is some trial evidence to suggest that the combination of ACE inhibitor and ARB may reduce hospitalisations, but there may be an adverse interaction in those patients also receiving a beta-blocker.14 Given that all patients should be on an ACE inhibitor and beta-blocker where tolerated, I remain very cautious in my use of ARBs.

Beta-adrenoceptor antagonists

The newest pharmacological agents for standard heart failure treatment are b-blockers. They have been shown unequivocally to work for all grades of heart failure,15, 16 including the most severe.17 At present, the situation is much the same as for ACE inhibitors when they were first widely recommended: uptake is very low.

There is sensible guidance on how to start a beta-blocker in the guidelines. The general rule is start low, and increase slowly.

As with ACE inhibitors, the agent chosen should be one used in a clinical trial showing benefit (carvedilol and bisoprolol: the preparation of metoprolol shown to be useful is not available in the UK). The dose should be increased gradually to that shown to be effective in trials (see Table 2).

Table 2: Dosing schedules for beta-blockers
Drug Starting dose Increment Interval Target
carvedilol 3.125mg bd doubling 2-4 weeks 25mg bd*
bisoprololÊ 1.25mg od doubling 2-4 weeks 10mg od
metoprolol 12.5mg od doubling 2-4 weeks 200mg odˆ

*50mg bd if over 85kg body weight;
Êbisoprolol was initiated in hospital in CIBIS II;
ˆmetoprolol is not licensed for heart failure treatment in the UK, and the preparation used in the MERIT-HF trial (metoprolol CR/XL) is not available in the UK

A common problem is the patient who develops symptoms of hypotension as drugs are increased, particularly the combination of ACE inhibitor and beta-blocker. There is little evidence to guide practice here. My view is that a patient is better off with a little bit of both than a full dose of either drug alone, and here the guidelines fail us.

Unhelpful drugs

An important issue in heart failure management is 'bad' drugs, or drugs that are of no benefit. Positive inotropic drugs (other than digoxin) should be avoided. Calcium antagonists are also best avoided; if truly necessary to control hypertension or angina, then amlodipine and felodipine are probably safe.

Antiarrhythmic agents should, in general, not be prescribed, despite the fact that arrhythmia is thought to be a common mode of death in heart failure. Amiodarone is probably the safest agent for heart failure patients where indicated, although dofetilide may be more widely used in future as it has fewer long-term side-effects.

Aspirin use remains controversial. Non-steroidal anti-inflammatory drugs are recognised as being deleterious in heart failure patients, yet it is widely believed that aspirin should be prescribed lifelong to any patient with coronary artery disease.

There is very little evidence to sustain this point of view. In short-term haemodynamic studies, aspirin antagonises the beneficial effects of ACE inhibitors,18, 19 and there is some evidence to suggest that this translates into an adverse effect on mortality.20

The guidelines avoid coming to a conclusion, stating that 'it would be inappropriate to make any recommendations' about aspirin. It does seem extraordinary that a drug should be so widely used when there is no evidence for its use.

Devices

Also new since the last set of guidelines are the proliferating devices available as adjunctive treatments for heart failure.

The most important of these is the implantable defibrillator. There is no doubt that this device should be implanted in a patient with sustained ventricular arrhythmia and poor left ventricular function.21 The indications for this treatment are only likely to widen as clinical trials are conducted in wider patient groups.

Re-synchronisation therapy with biventricular pacemakers shows promise, but there are insufficient data available for recommendations as yet.

Diastolic heart failure

Heart failure with normal systolic left ventricular function is another area of controversy. Some commentators think it rare, while others think it accounts for over half of all cases of heart failure. The ESC guidelines are brisk at this point, and rather skate past the issue. More trial evidence is needed before any guidelines about treatment in this patient group can be given.

Conclusions

CHF is common and lethal. We have available powerful agents that can approximately double life expectancy for the individual patient, yet we do not apply those treatments widely enough.

As important, we continue to use some agents of no proven benefit, such as aspirin. The importance of guidelines is in trying to encourage the medical profession to change its practice. The ESC Task Force has made a major contribution, but preaches mainly to the converted. However, much of heart failure care is provided by non-cardiologists who may not have ready access to the guidelines.

References

  1. Senni M, Tribouilloy CM, Rodeheffer RJ et al. Congestive heart failure in the community: a study of all incident cases in Olmsted County, Minnesota, in 1991. Circulation 1998; 98: 2282-9.
  2. Ho KK, Anderson KM, Kannel WB et al. Survival after the onset of congestive heart failure in Framingham Heart Study subjects. Circulation 1993; 88: 107-15.
  3. The CONSENSUS trial study group. Effects of enalapril on mortality in severe congestive heart failure: results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J Med 1987; 316: 1429-35.
  4. Witte K, Thackray S, Clark AL et al. Clinical trials update: IMPROVEMENT-HF, COPERNICUS, MUSTIC, ASPECT-II, APRICOT and HEART. Eur J Heart Fail 2000: 2: 455-60.
  5. Fonseca C, Ceia F, Brito D, Madeira H. How patients with heart failure are managed in Portugal. Eur J Heart Fail 2002: in press.
  6. Taskforce for the Diagnosis and Treatment of Chronic Heart Failure, European Society of Cardiology. Guidelines for the diagnosis and treatment of chronic heart failure. Eur Heart J 2001; 22 :1527-60.
  7. The Taskforce on Heart Failure of the European Society of Cardiology. Guidelines for the diagnosis of heart failure. Eur Heart J 1995; 16: 741-5.
  8. The Taskforce of the Working Group on Heart Failure of the European Society of Cardiology. The treatment of heart failure. Eur Heart J 1997; 18: 736-53.
  9. McDonagh TA, Robb SD, Murdoch DR et al. Biochemical detection of left-ventricular systolic dysfunction. Lancet 1998; 351: 9-13.
  10. Stewart S, Marley JE, Horowitz JD. Effects of a multidisciplinary, home-based intervention on unplanned readmissions and survival among patients with chronic congestive heart failure: a randomised controlled study. Lancet 1999; 354: 1077-83.
  11. Working Group on Cardiac Rehabilitation and Exercise Physiology and Working Group on Heart Failure of the European Society of Cardiology. Recommendations for exercise testing in chronic heart failure patients. Eur Heart J 2001; 22: 125-35.
  12. Anker S, Ponikowski P, Varney S et al. Wasting as an independent risk factor for mortality in chronic heart failure. Lancet 1997; 349: 1050-3
  13. Pitt B, Zannad F, Remme WJ et al for the Randomised Aldactone Study Investigators (RALES). The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 1999; 341: 709-17.
  14. Pitt B, Poole-Wilson PA, Segal R et al, on behalf of the ELITE II investigators. Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial„the Losartan Heart Failure Survival Study ELITE II. Lancet 2000; 355: 1582-7.
  15. CIBIS II investigators. The cardiac insufficiency bisoprolol study II (CIBIS-II): a randomised trial. Lancet 2000; 353: 9-13.
  16. MERIT-HF Study Group. Effect of metoprolol CR/XL in chronic heart failure: metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet 1999; 353: 2001-7.
  17. Packer M, Coats AJ, Fowler MB et al. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med 2001; 344: 1651-8.
  18. Hall D, Zeitler H, Rudolph W. Counteraction of the vasodilator effects of enalapril by aspirin in severe heart failure. J Am Coll Cardiol 1992; 20: 1549-55.
  19. Spaulding C, Charbonnier B, Cohen-Solal A et al. Acute hemodynamic interaction of aspirin and ticlopidine with enalapril: results of a double-blind, randomized comparative trial. Circulation 1998; 98: 757-65
  20. Cleland JG, Bulpitt CJ, Falk RH et al. Is aspirin safe for patients with heart failure? Br Heart J 1995; 74: 215-19.
  21. A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. The Antiarrhythmics versus Implantable Defibrillators (AVID) Investigators. N Engl J Med 1997; 337: 1576-83.

Guidelines in Practice, February 2002, Volume 5(2)
© 2002 MGP Ltd
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