Introduction

These notes are intended to summarise the main components of the management of patients with suspected and confirmed heart failure due to left ventricular systolic dysfunction, including diagnosis and chronic management as well as the immediate management of acute left heart failure.

Clinicians are directed to other guidelines for further details of the evidence base, for example 

Primary care clinicians may wish to review the diagnosis and management of patients with a previous diagnosis of heart failure (“the prevalent pool”) as well as those with new presentation suspected or definite heart failure (incident cases).

Heart failure is a clinical syndrome characterised by a set of signs and symptoms consistent with fluid retention and impaired cardiac function. These include fatigue, dyspnoea, raised jugular venous pressure, pulmonary and peripheral oedema. It is important to;

  1. Ensure that the diagnosis of heart failure is accurate and that there is no another explanation for the symptoms. Approximately 50% of the prevalent pool of patients in primary care labelled as having heart failure may not have left ventricular systolic dysfunction [1].
  2. Define the aetiology. Many patients have heart failure due to left ventricular systolic dysfunction, but it is important to ensure that this is the case. It is important to remember that two conditions may occur in the same patient, for example, patients with atrial fibrillation may have systolic dysfunction. 

Other causes of heart failure include;

In the case of left ventricular systolic dysfunction to try and identify the underlying aetiology of this eg 

In patients with systolic dysfunction, a reversible cause must be excluded eg severe aortic or mitral regurgitation. If there is any doubt a specialist assessment should always be obtained. Anaemia and thyrotoxicosis can exacerbate heart failure.

This strategy refers to the management of heart failure due to left ventricular systolic dysfunction.


Diagnosis of heart failure

Patients presenting to primary care may be categorised following initial assessment into;

History 

Patients may present to primary care with a number of symptoms which may be due to heart failure. Breathlessness, tiredness and ankle swelling are all symptoms attributable to heart failure, but are non-specific and many people with these symptoms will not have heart failure. Symptoms such as orthopnoea and paroxysmal nocturnal dyspnoea (PND) are more specific, but are only present in a small proportion of patients with heart failure [3].    

  Sensitivity Specificity
Dyspnoea  66%  52%
Othopnoea  21%  81%
PND  33%  76%
Oedema   23% 80%

Others have suggested that dyspnoea may be more sensitive and Davis et al reported a sensitivity of 100% and specificity of 17% in a primary care population with suspected heart failure secondary to left ventricular systolic dysfunction referred for open access echocardiography [4]. There was a consensus by the local group that ankle oedema may be less specific in an unselected primary care population. In clinical practice it is the combination of symptoms and signs, and the presence or otherwise of a likely cause of heart failure which are most useful rather than any of these in isolation.

People with heart failure will usually have a condition to explain why heart failure has developed. The commonest cause of heart failure in the UK today is coronary heart disease and a previous history of a myocardial infarction makes the diagnosis of heart failure more likely. Some patients may have had a silent MI (this should be particularly considered in people with diabetes). Other causes of heart failure include long standing hypertension and alcohol excess. A smaller proportion of patients have valvular heart disease (? murmur, ? history of rheumatic fever).

Examination 

Clinical examination is also helpful, and the following makes the diagnosis of heart failure more likely [3]; 

  Sensitivity Specificity
Tachycardia  7%  99%
Rales   13% 91%
Third heart sound   31% 95%
Raised JVP   10% 97%
Oedema  10%  93%

The likelihood that a patient has left ventricular dysfunction also varies with the combination of symptoms and signs. For example [4],

  Sensitivity Specificity
Prior MI & gallop or crackles   24% 98%
Displaced apex beat & prior MI   39% 99%
Displaced apex beat & crackles or raised JVP or gallop   44% 99%

Investigation

ECG An ECG can provide very useful information. Left ventricular systolic dysfunction was unlikely in a primary care population if there was no major abnormality on the ECG (sensitivity 94%, NPV 98%) [5]. Although most studies support this finding, there are contrary data published including one report in which 27% of cases had a normal ECG [6]. Thus, in patients with breathlessness and a normal ECG alternative causes might be considered first, although patients must be investigated further (for example with echocardiography) if heart failure is still thought to be the likely diagnosis.
CXR A chest X-ray may provide useful information. Cardiomegaly may be present (cardiothoracic ratio (CTR) > 0.50 on standard PA CXR). The prevalence of an increased CTR has been reported in some of the large heart failure trials:
 
  CTR > 0.50 CTR > 0.55
SOLVD - treatment 57%  -
DIG 60%  35%

It may also show pulmonary congestion or another explanation for breathlessness such as a lung tumour.

Echocardiograph  All patients in whom the diagnosis of heart failure cannot be excluded require an assessment of left ventricular function. Patients in whom the diagnosis of heart failure is secure may also be considered for an assessment of left ventricular function as an indicator of prognosis. The echocardiograph is the most frequently used investigation, but may not be possible in approximately 10% patients due to technical reasons and alternative investigation may be necessary. Atrial fibrillation also makes the assessment of left ventricular function less reliable. Some patients may have had an alternative method of estimate of left ventricular function in secondary care eg gated heart scan, left ventriculography during coronary angiography.

“The prevalent pool”

There are patients who have been treated for some time with diuretics for suspected heart failure (“the prevalent pool”). Generally, these patients are more likely to need a formal assessment of left ventricular function (for example by echocardiography) before left ventricular systolic dysfunction can be excluded as the symptoms and signs may be masked by treatment.

It is also important to note that patients with previously documented heart failure secondary to left ventricular systolic dysfunction and treated with ACE inhibitors may have apparently normal left ventricular systolic dysfunction after a period of time. Left ventricular function may deteriorate in these patients if ACE inhibitors and other treatments are withdrawn. Thus, any decision to withdraw treatment in these patients must be made only after a full review of the circumstances in which the diagnosis of heart failure was made and not just from the results of an echocardiograph. Any treatment plan to withdraw treatment must incorporate planned reviews over a period of time, pragmatically probably over the following 3 months.


Assessment of patients with left ventricular systolic dysfunction

The aims of assessment are to

Identify exacerbating conditions/drugs

Anaemia, thyrotoxicosis, and renal failure may all exacerbate heart failure. Drugs include most calcium channel blockers, some anti arrhythmic drugs, NSAIDs etc

Routine investigations 

These are minimum requirements

It is recommended that an echocardiograph or other assessment of left ventricular dysfunction is made if at all possible, as an aid to prognostic assessment, but is not always necessary to make the diagnosis of left ventricular systolic dysfunction.

The recently published NICE guidance about implantable cardiac defibrillators will lead to an increase in other investigations such as 24 hour Holter monitoring. Regional guidelines are currently being prepared and should be referred to when available.

Symptomatic limitation

The most frequently used classification is the New York Heart Association (NYHA) classification. The grading refers to symptoms.

New York Heart Association classification of heart failure symptoms

Class I  No limitations. Ordinary physical activity does not cause undue fatigue, dyspnoea or palpitation (asymptomatic left ventricular dysfunction).
Class II  Slight limitation of physical activity. Such patients are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnoea or angina pectoris (symptomatically mild heart failure).
Class III  Marked limitation of physical activity. Although patients are comfortable at rest, less than ordinary physical activity will lead to symptoms (symptomatically moderate heart failure).
Class IV  Inability to carry on any physical activity without discomfort. Symptoms of congestive cardiac failure are present even at rest. With any physical activity increased discomfort is experienced (symptomatically severe heart failure).

Prognosis

There are many univariate predictors of reduced survival in patients with left ventricular systolic dysfunction and these notes are not intended to list all of them. However, some pointers may be helpful when talking to patients in clinical practice.

The prospective studies of ACE inhibitors have shown a strong relationship between functional class and mortality. The following estimates are intended as a guide only. It is important to note that these apply to patients not treated with ACE inhibitors or other drugs to improve prognosis.

Treatment with drugs such as ACE inhibitors and beta blockers can lead to substantial improvements in predicted survival. For example, in the recent CIBIS II trial [7] in which 83% patients were YHA Ill the addition of bisoprolol to standard treatment (nearly all were taking ACE inhibitors) reduced the estimated annual mortality from 13.2% to 8.8% (see below for more details).

Patients with more severely impaired left ventricular function have a worse prognosis, but there is not predictable relationship between the degree of left ventricular impairment and functional limitation and relying on left ventricular function alone to estimate predicted survival in the individual patient is not always very sensitive.

Other simple markers of an adverse outcome include low serum sodium and impaired renal function, and an ischaemic aetiology for the cardiomyopathy.

Appropriate referral and follow up

The following patients should be considered for referral for specialist assessment;

  1. Patients should not be referred if co- morbidity makes this inappropriate, or the patient declines. 
  2. Patients with poorly controlled symptoms not responding to treatment 
  3. All patients with angina and heart failure. 
  4. Some patients for drug initiation and dose up titration. 
  5. For clarification of the aetiology of left ventricular systolic dysfunction. 
  6. Appropriate patients with known coronary disease may also be referred for consideration of coronary artery bypass graft surgery for prognostic reasons. 
  7. All patients with haemodynamically significant valve disease (or if there is doubt that this is the case). 
  8. Patients in atrial fibrillation in whom cardioversion (or alternative non pharmacological treatments) might be considered. 
  9. All patients with definite heart failure (eg definite pulmonary congestion on a CXR) with normal left ventricular systolic function on echocardiograph should be referred for specialist assessment. 
  10. Patients in whom the diagnosis is not secure and in whom echocardiographic images cannot be obtained or the quality is too poor for an accurate assessment of left ventricular function. 
  11. Patients who may benefit from other interventions eg patients who may benefit from transplantation. The role of other interventions, such as revascularisation, bi ventricular pacing etc will become clearer with time. 
  12. Patients in whom their employment is threatened.

Treatment of patients with left ventricular systolic dysfunction

A holistic approach to the treatment of patients with heart failure is vital. The aims of treatment are to improve quality of life by;

Non-pharmacological interventions

Diet Salt  Dietary salt should be reduced as much as possible by avoiding the intake of salt rich foods.
  Fluid intake  Excessive fluid intake should be avoided.
  Obesity  Obesity should be reduced. Patients should be advised about setting realistic targets to reduce body weight. This will require counselling about behaviour change as well as nutritional advise. Management strategies are outlined in the district obesity policy.
  Cachexia  This should be managed in conjunction with a dietician. Meals may need to be small and often, and advice given about the nutritional content. For example, fat soluble vitamins may be poorly absorbed, diuresis may lead to a loss of water soluble vitamins.
Alcohol  Alcohol should be avoided completely in patients with alcohol induced cardiomyopathy. In other patients with heart failure, alcohol can be consumed in small amounts, for example 1-2 units per day.
Smoking  Patients should be advised to stop smoking and their readiness to do so assessed. Those motivated to stop should be offered access to intermediate or specialist smoking cessation advice in line with the district smoking cessation strategy. Those who are not motivated to stop should be able to access smoking cessation advice later if they wish.
Exercise  Appropriate exercise is beneficial for patients with stable heart failure and structured programmes for patients with heart failure, including long term maintenance, are to be developed in the future.
Education This includes the following;
  • Education about heart failure 
  • Lifestyle advice (see above) 
  • Information about drugs and the need for compliance. 
  • Explanation about the symptoms of worsening heart failure and the appropriate action to be taken. 
  • Explanation of the adverse effects of medication, and the appropriate action to be taken if they occur. 
  • Social activity, employment and travel.
Immunisation Once only pneumococcal vaccination and annual influenza immunisation.
Cardiac rehabilitation Some of the above interventions, and others, might be offered through a programme of cardiac rehabilitation. Cardiac rehabilitation should be tailored to the individual needs of the patient dependent on local provision.
Other interventions Coronary artery bypass surgery may improve the symptoms and prognosis of patients with heart failure and angina. There was a consensus in the group to recommend that all patients with heart failure and angina should be referred for a specialist opinion if the patient agrees and there is no other significant co morbidity. Percutaneous intervention (PCI) has not been shown to be of prognostic importance and patient selection for this must be carefully performed.

Volume reduction surgery / remodelling surgery may have a role in selected individuals. Cardiac transplantation is indicated where there are not alternatives, and where the patient is accepted on to the transplant programme.

Bi ventricular pacing has recently been advocated as an alternative symptomatic approach. Further work on this is on going and results are awaited.

Implantable cardiac defibrillators (ICD) have been shown to reduce mortality in selected patients at high risk of malignant arrhythmias. Patients should be managed within the recommendations of the regional guidelines for ICDs once these are published.

Palliative care services Studies have shown that people with significant heart failure have similar high levels of symptoms such as pain, dyspnoea, anxiety and depression to those experienced by people with malignant conditions. These people would benefit from the palliative care approach that is more commonly applied to people with cancer. This requires a comprehensive assessment of physical, psychological and social problems and appropriate symptom relief. Consideration should be given to;
  • Relief of physical symptoms such as pain and dyspnoea 
  • Detection and management of psychological problems - anxiety, depression 
  • The need for social support for patients and their carers 
  • Full opportunity to discuss the prognosis and consequences of their illness

Patients with complex problems may benefit from referral to specialist palliative care teams.

Social support Appropriate social support should be offered.

Pharmacological interventions

This is intended to summarise the drug treatments which should be considered in patients with left ventricular systolic dysfunction. It is assumed that individual contra indications will be excluded. Some patients may not tolerate individual drugs. It is good clinical practice to record this and the reason in the notes. However, patients should not be recorded as intolerant when alternatives might not have been considered. For example, patients who develop symptomatic hypotension taking an ACE inhibitor and diuretic may benefit from a reduction in the dose of diuretic, and not have to reduce or stop the ACE inhibitor. Clinicians should refer to other sources of information eg BNF

Diuretics (see below for spironolactone) Patients with signs of fluid overload require treatment with a diuretic. Patients who are breathless, but who do not have clear signs of pulmonary oedema often also benefit.

Monitoring of renal function and serum potassium is mandatory.

Most symptomatic patients require a loop diuretic. In some with mild symptoms of heart failure a thiazide may be sufficient, but is less effective in patients with renal failure and is associated with a higher incidence of hyponatraemia. In a few patients with severe heart failure and resistant oedema the combination of a loop and thiazide diuretic is very effective, but doses must be appropriate and the effects, including on serum sodium, potassium and renal function, must be monitored closely.

Some hospital specialists consider the combination of a loop diuretic and for a thiazide (for example Bendroflumethazide 1.25mg - 2.5 mg daily) once a patient is taking furosemide 80mg - 160mg daily. In a few patients with very resistant fluid retention despite optimising other treatment metolazone may be considered in combination with a loop diuretic (usually under hospital supervision). However, bendroflumethazide 10mg daily and metolazone 10mg daily for 3 days are equally effective, while longer courses add no benefit [8].

In an outpatient setting, self-medication with metolazone 2.5mg b.d. for up to 2 days in the event of deterioration may prevent readmissions in patients able to self-monitor [9]. The successful use of demeclocycline in resistant cases has also been reported [10].

ACE Inhibitors All patients with left ventricular systolic dysfunction, including those who are asymptomatic should be treated with ACE inhibitors unless there are contra indications.

ACE inhibitors have been shown to reduce symptoms and signs of heart failure, and improve exercise capacity. Mortality and hospital admission are reduced [11, 12]. A recent overview reported a 20% reduction in mortality and 33% reduction in readmission for heart failure [13]. The benefits were seen early after the start of treatment and persisted long term. There was a trend towards greater risk reductions in those with the lowest ejection fractions.

The SOLVD prevention trial [14] reported a reduction in progression to symptomatic heart failure from ACE inhibitor treatment. The reduction in total mortality was not statistically significant, but there was a trend.

Initiation and monitoring of ACE inhibitors

Renal function and serum potassium must be monitored before initiation, each dose up titration and periodically thereafter. The North of England Guidelines for the use of ACE inhibitors in the primary care management of adults with symptomatic heart failure [15] recommend that a baseline assessment of blood pressure, renal function and potassium is performed in all patients, and repeated 1 week after initiation and dose up titration. Thereafter, treatment should be monitored periodically, eg at least annually, or more frequently if patients become unwell or have impaired renal function. Treatment modification (which may be a reduction in the dose of diuretic, not always the ACE inhibitor) is advised if any of the following develop;

  • an increase in creatinine of 50 micromol/l or more, 
  • a serum potassium of 5.5 mmol/l of higher, 
  • symptomatic hypotension (a documented fall in blood pressure with dizziness or weakness)

Particular vigilance is recommended (and hospital referral if necessary) in some patients. For example;

  • those with a serum sodium < 135mmol/l, 
  • a creatinine > 150micromolll, 
  • a systolic blood pressure < 100mmHg, 
  • treatment with furosemide 80mg daily or more, 
  • those with severe symptoms of heart failure and or peripheral vascular disease.

ACE inhibitors are started at a low dose (eg lisinopril 2.5 mg od, enalapril 2.5 mg bd) and should be up titrated to at least the doses shown to have been effective in the trials eg Lisinopril 20mg od, enalapril 10-20mg bd [11, 14], or the maximum tolerated.

The ATLAS study [16] compared lisinopril 2.5 -5 mg od with 32.5 —35 mg ad and reported a non significant 8% reduction in mortality and a significant 12% reduction in the combined end point of death and hospital admission for any reason. However, the NETWORK trial [17] which studied three enalapril regimens (2.5mg bd, 5mg bd, 10mg bd) reported no difference in mortality or the combination of mortality, hospital admission or worsening heart failure after 6 months. A 12 month study comparing enalapril 10 mg bd and 30 mg bd also reported no difference between the two groups [18]. At present it is recommended that the dose of ACE inhibitors is uptitrated to the doses in the major heart failure trials (see above).

Spironolactone  Patients with severe heart failure and left ventilcular systolic dysfunction should be treated with low dose spironolactone (25mg od) unless there are contra indications.

Monitoring of serum potassium is mandatory.

The addition of spironolactone has been shown to reduce mortality and hospitalisation for severe heart failure. The RALES trial [19] was stopped early after a mean follow up of 24 months because an interim analysis reported a 30% reduction in mortality and 35% lower frequency of hospitalisation. Patients in the trial had severe heart failure, all were taking loop diuretics and 94% ACE inhibitors.

Beta blockers  Stable patients with controlled mild to moderate heart failure and left ventricular systolic dysfunction should be treated with beta blockers in addition to diuretics and/or digoxin and ACE inhibitors unless there are contra indications.

The addition of beta blockers to diuretics, ACE inhibitors and digoxin has been shown to reduce mortality 35% in patients with mild to moderate heart failure [7,20,21]. A recent trial has reported similar results in patients with severe heart failure [22].

Both carvedilol and bisoprolol are licensed for use as adjunctive treatment in mild to moderate heart failure. The MERIT trial used metoprolol as a slow release preparation. At present, there is insufficient evidence to recommend the use of one particular beta blocker. If patients taking a different beta blocker (eg atenolol) develop mild heart failure it is reasonable to suggest they continue this if they are tolerating it.

Initiation and dose up titration of bate blockers 

The starting dose of beta blocker is substantially lower than conventional doses eg carvedilol 3.125 mg bd, bisoprolol 1.25 mg ad. The dose is up titrated at intervals of 2 weeks or more.

Beta blocker Starting dose Target dose (or max tolerated)
Carvedilol 3.125 mg bd 25mg bd (if weight < 85kg) 

50mg bd (if weight > 85kg)

Bisoprolol 1.25 mg od  10 mg od

The current recommendations are that initiation should be under the Supervision of a hospital consultant. It is expected that as experience with the use of these drugs in patients with heart failure extends, GPs will also initiate beta blockers in some patients.

What to do if patients taking beta blockers develop heart failure

There is no evidence on which to base recommendations but these are a few thoughts. However, they are intended as ideas and clinical judgement must be exercised.

  • Mild deterioration - continue beta blocker and treat with additional standard anti failure treatment (diuretics etc). Review in few days. If no or slow improvement, increase anti failure treatment and consider halving the dose of beta blocker (increasing again after an interval once failure resolved).
  • Moderate deterioration - some may need admission to hospital. If not, treat with additional standard anti failure treatment (diuretics etc) and consider halving the dose of beta blocker. Review in few days. If these patients do not improve or deteriorate further the beta blocker may need to be temporarily withdrawn, and admission to hospital is likely to be necessary.
  • Severe deterioration - admission to hospital.
Digoxin  Digoxin is indicated in patients in sinus rhythm treated with diuretics, and ACE inhibitors if possible, who remain symptomatic, particularly those who have had at least one admission to hospital.

Digoxin is also indicated in patients with heart failure and atrial fibrillation with a rapid ventricular response.

Withdrawal trials have shown withdrawal of digoxin from patients with heart failure in sinus rhythm leads to deterioration in symptoms and exercise tolerance [23]. A placebo controlled trial reported an overall neutral net effect on mortality (balance between reduction in death due to worsening heart failure and an increase in death due to other cardiac causes eg arrhythmias) and a 28% reduction in hospitalisation for heart failure [24].

Digoxin dose The median daily dose of digoxin in the DIG trial was 0.25 mg. The mean plasma concentration was 0.88 ng/ml at 1 month and 0.80 ng/ml at 1 year.

AT II antagonists It is accepted practice to consider an angiotensin II receptor antagonist in patients unable to tolerate an ACE inhibitor due to cough (check the cough is not due to pulmonary oedema first), rash or angio oedema.

Trials comparing losartan with captopril have reported at least similar outcomes with losartan as with captopril [25, 26].

Preliminary results from Val-HeFT (valsartan in heart failure) were presented at the 73rd Scientific Sessions of American Heart Association and reported an additional benefit from adding valsartan to standard background treatment for heart failure, including an ACE inhibitor, with a significant reduction in the primary end point of combined all cause mortality and morbidity. However, there may be interactions with other treatments such as ACE inhibitors and beta blockers and the publication of this trial is awaited. At present the addition of an angiotensin receptor II antagonist to other standard treatment cannot be recommended, although it is reasonable to suggest its use as a substitute for the ACE inhibitor if cough is troublesome or with allergy to ACE inhibitors (it is not an alternative to an ACE inhibitor when the problem is one of renal dysfunction). This may be revised as new evidence becomes available.

Hydrallazine/nitrate Patients treated with diuretics and or digoxin who are unable to tolerate an ACE inhibitor due to development of renal failure should be considered for treatment with hydrallazine and oral nitrate.

The target doses in the trials were total daily doses of hydrallazine 300 mg and isosorbide dinitrate 160 mg, taken in a four times per day regimen.

The mortality of patients treated with a combination of hydrallazine and oral isosorbide dinitrate was lower than those treated with other prazosin or placebo [27], although mortality was lower in patients treated with enalapril than with hydrallazine and nitrate [28].

Warfarin/Aspirin  Both aspirin and warfarin have been shown to reduce further coronary events in patients with coronary artery disease and one or other should be considered in these patients [29].

Patients in atrial fibrillation should be considered for treatment with warfarin with a target INR of 2.5.

For patients in sinus rhythm there is insufficient evidence on which to recommend either warfarin or aspirin to prevent thrombo-embolism, although some patients at higher risk may be treated with warfarin eg peri partum cardiomyopathy.

Nitrates  Nitrates may be used in combination with hydrallazine, or to treat symptoms of angina in patients with chronic heart failure.
Anti anginals  Beta blockers and nitrates have been discussed. Some calcium antagonists may precipitate or aggravate heart failure (eg nifedipine, diltiazem). Trials have reported that amlodipine is safe to use in patients with heart failure [30]. Felodipine is also reported to be well tolerated [31].
Statins  Statins should be prescribed to patients who are likely to benefit (see the local statin strategy - FATS).

Management of acute left heart failure

Patients with severe symptoms should be admitted to hospital.

A treatable cause such as myocardial infarction or arrhythmia should always be sought and treated. Basic treatment measures are to sit the patient upright and give high flow oxygen (controlled oxygen in COPD patients). Initial drug treatment is with intravenous loop diuretics (e.g. furosemide 80mg), diamorphine (2.5.5mg, caution in COPD) and buccal or intravenous nitrates. Second line treatments include dobutamine, especially if the systolic blood pressure is below l00mmHg. Bronchodilators such as beta -2 agonists or aminophylline may be used if wheezing is present - 'cardiac asthma'. These agents, particularly aminophylline, increase the risk of cardiac arrhythmias and should be used with caution. Mechanical ventilation may be necessary in severe cases with respiratory failure. Intra aortic balloon counterpulsation may be used in selected cases in whom further definitive treatment is being considered.

Following initial 'rescue therapy', ACE inhibitors and other treatments described in this guideline should be started. Initiation of beta blockers should be delayed until the patient is stable on other treatment

The re admission rate of patients with heart failure is high (40%+). This may be reduced by ensuring the following;

In some patients the goals may need reassessing: very ill, recurrent admission.


References

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Appendix

Membership of the final guideline development group