Heart failure is the inability of the heart to cope with its workload of pumping blood to the lungs and to the rest of the body. Heart failure can primarily affect either the right or the left side of the heart; however, it most commonly affects both sides. Heart failure can be acute or chronic (congestive).
Types and Causes
Left-sided heart failure
Left-sided failure may be due to hypertension (high blood pressure), anaemia, hyperthyroidism (over-activity of the thyroid gland), a heart valve defect (such as aortic stenosis, aortic incompetence, or mitral incompetence), or a congenital heart defect. In all of these conditions, the left side of the heart must work harder than normal to pump the same amount of blood. Sometimes, the heart can compensate for the extra workload by an increase in the size of the left side and in the thickness of its muscular walls, or by an increase in the heart rate. This compensation is only temporary, however, and heart failure eventually follows.
Other causes of left-sided heart failure include coronary artery disease, myocardial infarction (heart attack), cardiac arrhythmias (irregularities of heart rhythm), and cardiomyopathy (disease of the heart muscle). In cardiomyopathy, the pumping power of the heart is reduced to a point where it can no longer deal with its normal workload. Whatever the underlying cause, in left-sided heart failure the left side of the heart fails to empty completely with each contraction, or has difficulty in accepting blood that has been returned from the lungs. The retained blood creates a “back pressure” that causes the lungs to become congested with blood. This condition leads to pulmonary oedema (excess fluid in the lungs), of which the main symptom is shortness of breath, eventually even when at rest. The patient may awaken at night with attacks of breathlessness, wheezing, and sweating.
Right-sided heart failure
Right-sided failure is most often caused by pulmonary hypertension (raised blood pressure in the arteries supplying the lungs). This is itself caused by left-sided heart failure, or a lung disease such as chronic obstructive pulmonary disease (see chronic obstructive pulmonary disease). Right-sided failure can also be due to a heart valve defect, such as tricuspid incompetence, or to a congenital heart defect. In all types of right-sided heart failure, there is back pressure in the circulation from the heart into the venous system, causing swollen neck veins, enlargement of the liver, and oedema (excess fluid in body tissues), especially swelling of the legs and ankles. In addition, the intestines may become congested, causing discomfort and indigestion.
Investigation and Treatment
Investigation of suspected heart failure may involve a physical examination, X-ray, ECG, and echocardiography. Attacks of acute heart failure may subside of their own accord or may require urgent, life-saving treatment. Immediate treatment of heart failure consists of bed rest, with the patient sitting up. Diuretic drugs are given to increase the output of urine from the kidneys, thereby ridding the body of excess fluid and reducing blood volume. Morphine and oxygen may be given as emergency treatment in acute left-sided heart failure. Long-term drug treatment usually involves the use of ACE inhibitor drugs and diuretics. Angiotensin-II antagonists, other vasodilator drugs, and beta blocker drugs may also be required. If heart failure is associated with atrial fibrillation, digoxin will most likely be prescribed to control the heart rate. Other possible treatments of heart failure include fitting a pacemaker, coronary artery bypass, and heart transplant.
Heart Failure in detail - technical
Heart failure is a clinical syndrome that results from any structural or functional cardiac disorder that reduces the ability of the heart to function as a pump. It affects 1 to 2% of the population, and mortality may be as high as 30% in the year after diagnosis, falling to between 5 and 10% annually thereafter with best treatment. The most common underlying pathophysiological abnormality is systolic dysfunction of the left ventricle (LV), but a few patients—particularly elderly people—have no obvious valvular or systolic impairment of the heart and are assumed to have diastolic abnormalities.
Clinical features and diagnosis—heart failure is usually associated with dyspnoea, fatigue, and fluid retention, but these are nonspecific, hence diagnosis depends on careful clinical examination supplemented by tests, in particular echocardiography. Measurement of the plasma concentration of B-type natriuretic peptide (BNP) is the best test for ruling out heart failure in a particular patient.
Treatment usually involves lifestyle measures and drug therapy. Implantable devices, such as pacemakers and cardioverter-defibrillators, are being used increasingly, but surgical interventions only apply to a few patients.
Lifestyle measures—few recommendations are supported by a large evidence base, but those that are widely advised include salt restriction (with a maximum daily intake of 6 g), smoking cessation, and supervised exercise training.
Drug therapy—most of the evidence base for the management of heart failure relates to heart failure due to LV systolic dysfunction—‘systolic heart failure’; the best management for heart failure due to valvular disease or diastolic heart failure is less clear. Relating to particular drugs (1) diuretics—these are the most effective means of removing retained fluid, and their introduction often produces rapid symptomatic relief; (2) angiotensin-converting enzyme (ACE) inhibitors—in chronic heart failure these reduce the relative risk of death by 23% and of worsening heart failure by 35%; (3) angiotensin receptor blockers (ARBs)—proven in randomized trials to reduce the risk of mortality and heart failure deterioration, and now generally used in patients who cannot tolerate an ACE inhibitor due to cough; (4) β-blockers—reduce the relative risk of death by about 25% and reduce the risk of death from heart failure by 35%; (5) spironolactone—reduces the risk of death by 30% in patients with moderate to severe heart failure despite treatment with diuretic and ACE inhibitor; eplerenone is a more selective aldosterone antagonist that is often prescribed in place of spironolactone if gynaecomastia develops while on that drug. However, it is important to recognize that the treatment of patients with heart failure with diuretics and/or ACE inhibitors or ARBs and/or β-blockers and/or spironolactone (or eplerenone) is often difficult, with problems arising from hypotension, bradycardia, hyperkalaemia, and deterioration of renal function. Close monitoring and careful clinical judgement are required.
Cardiac resynchronization—up to 20% of patients with heart failure have mechanical dyssynchrony due to native left bundle branch block, which means that the interventricular septum and lateral free wall of the LV do not contract at the same time, reducing the efficiency of pumping. An atriobiventricular pacing system, where conventional right atrial and right ventricular pacing wires are supplemented by a third lead placed in a lateral coronary vein via the coronary sinus to allow pacing of the LV system, can reduce the dyssynchrony (cardiac resynchronization therapy, CRT). Large clinical trials have demonstrated that this can produce a substantial reduction in mortality (up to 40%) in patients with left bundle branch block and moderate to severe symptoms of heart failure despite optimal drug therapy, and recent studies indicate that some patients with less severe disease can also benefit. The risk of sudden cardiac death can be further reduced by combining CRT with an implantable cardioverter defibrillator (ICD).
End of life—palliative care skills are an important component of good management of heart failure.
Heart failure is a clinical syndrome that results from any structural or functional cardiac disorder that reduces the ability of the heart to function as a pump. Any condition that damages the heart can lead to heart failure.
Heart failure is not in itself a complete diagnosis, which requires consideration of the underlying abnormality of the heart, the severity of the syndrome, the aetiology, the precipitating and exacerbating factors, the identification of concomitant disease relevant to management, and an estimation of prognosis. The diagnosis has serious implications both for the patient and the health care system. Mortality may be as high as 30% in the year after diagnosis, but with optimal drug and device therapy drops to between 5 and 10% annually thereafter. In addition, heart failure impacts on quality of life more than almost any other chronic medical condition. Comorbidity—such as renal dysfunction, cognitive impairment, and chronic airways disease—is common and may complicate management.
Heart failure is common, affecting 1 to 2% of the population, with the average age at diagnosis being 75 years. The management of heart failure accounts for 1 to 2% of the health care budget of most developed countries, largely due to the cost of the often lengthy hospitalizations required to restabilize the syndrome after deterioration.
Diagnosis is increasingly straightforward as a result of improvements in cardiac imaging and biochemical assays. Treatment has changed markedly in the past two decades through better understanding of the underlying pathophysiology and many large clinical trials of drug and devices. In a rapidly changing field, communication between health care professionals, education of patients and carers, and better chronic disease management remain key to improving patient outcomes.
Heart failure is usually associated with dyspnoea, fatigue, and fluid retention. Other symptoms may include nocturia, anorexia, abdominal bloating and discomfort, constipation, and cerebral symptoms such as confusion, dizziness, and memory impairment. None of these symptoms is specific for heart failure, and several other conditions can present in the same way (see box below). Symptoms alone cannot therefore be relied upon to make the diagnosis: good clinical skills with history taking and a careful physical examination need to be supplemented by further tests.
Box: Other conditions that may present with symptoms similar to heart failure
- ◆ Obesity
- ◆ Chest disease—including lung, pleura, diaphragm, or chest wall disease
- ◆ Venous insufficiency in lower limbs
- ◆ Drug-induced ankle swelling (e.g. amlodipine, nifedipine, felodipine)
- ◆ Drug-induced fluid retention (e.g. steroids, NSAIDs)
- ◆ Hypoalbuminaemia
- ◆ Intrinsic renal or hepatic disease
- ◆ Pulmonary embolic disease
- ◆ Depression and/or anxiety
- ◆ Severe anaemia
- ◆ Severe thyroid disease
- ◆ Bilateral renal artery stenosis
Useful tests in patients with suspected heart failure
A patient with suspected heart failure should have the following investigations:
- ◆ 12-lead electrocardiogram (ECG)
- ◆ Chest radiograph—principally to exclude other conditions such as lung cancer or pneumonia, but it may help confirm the diagnosis if it shows cardiomegaly and pulmonary congestion
- ◆ Blood biochemistry (including urea, creatinine, glucose, electrolytes), haemoglobin, thyroid and liver function tests, and blood lipids
- ◆ Serum natriuretic peptides (when available)
- ◆ Urinalysis to detect proteinuria or glycosuria
- ◆ Cardiac imaging—usually a transthoracic echocardiogram, which can rapidly provide detailed information about the structure and function of the cardiac chambers, valves, and pericardium
The algorithm for the diagnosis of heart failure currently recommended by the National Institute for Health and Clinical Excellence (NICE) in the United Kingdom is shown in the figure below (and see link to pdf of NICE guidelines in full). Measurement of serum natriuretic peptides and echocardiography are recommended as the key diagnostic tests, with echocardiography being most generally available.
See link to NICE (UK) Guidelines (August 2010) ref Heart Failure: http://pathways.nice.org.uk/pathways/chronic-heart-failure#path=view%3A/pathways/chronic-heart-failure/chronic-heart-failure-diagnosis.xml&content=view-index
The tests listed above will not only help confirm the clinical diagnosis, but will also help exclude other pathologies that may masquerade as heart failure, such as respiratory conditions, severe anaemia, or renal disease. They may also identify comorbidities that can influence management. In most cases the investigations described will rapidly confirm the clinical diagnosis of heart failure, but some cases may be more difficult and the input of a specialist may be required.
If the resting ECG is completely normal then heart failure due to left ventricular (LV) systolic dysfunction is unlikely. A better ‘rule out’ test, when available, is measurement of the plasma concentration of B-type natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP). For patients with new symptoms, heart failure (whatever the cause) is unlikely if the BNP level is low (<100 pg/ml), and other conditions should be considered first. If either (or both) the ECG and BNP are abnormal, then further cardiac investigation is likely to prove worthwhile, with imaging of the heart being the key test to confirm cardiac dysfunction.
The ECG is useful for reasons other than helping to exclude heart failure. It can confirm a clinical diagnosis of atrial fibrillation, and may give clues as to the aetiology of heart failure (e.g. Q waves from previous myocardial infarction; voltage criteria for LV hypertrophy in hypertension, aortic stenosis or hypertrophic cardiomyopathy). It may also indicate where a pacemaker may be required—such as in complete heart block—or where cardiac resynchronization therapy may be useful (left bundle branch block).
The most common underlying pathophysiological abnormality of the heart in patients with heart failure is systolic dysfunction of the LV. The ventricle contracts poorly in systole and is usually dilated. The term ‘systolic heart failure’ is often applied to this condition, which is easily detected by echocardiography (or cardiac MRI). A few individuals with heart failure, particularly elderly patients, have no obvious valvular or systolic impairment of the heart and are assumed to have diastolic abnormalities. This is more likely if there is a history of hypertension. A definitive diagnosis can only be made at cardiac catheterization, but the echocardiogram may give some pointers towards this diagnosis.
Doppler echocardiography provides useful information on overall LV systolic function, regional wall motion abnormalities (suggesting previous myocardial infarction), LV wall thickness, indirect assessment of diastolic function through Doppler measurement of flow through the mitral valve in diastole or by measurement of movement of ventricular walls during diastole (M-mode measurements or Tissue Doppler), assessment of structure and function of the cardiac valves, indirect estimation of pulmonary artery pressure, and assessment of right ventricular function. It is important that the echocardiogram is performed by a trained operator on high resolution equipment, with interpretation of results depending on the clinical situation.
In some patients, often those who are obese or who have chronic airways disease, echocardiography does not provide useful images. Cardiac MRI is particularly useful in such cases. Radionuclide blood pool multiple gated acquisition (MUGA) scanning can also provide an accurate estimation of the systolic function of the left ventricle, but does not detect valve dysfunction and exposes the patient to radiation.
Determining the aetiology of heart failure
Determining the underlying cause of heart failure is important in that treatment for primary valve disease differs from treatment for LV systolic impairment, and several causes of heart failure have a strong genetic component with implications for family screening and counselling regarding reproduction (e.g. hypertrophic cardiomyopathy). Echocardiography is very useful, in addition to good history taking and clinical examination, in determining the most likely aetiology, with the most common causes listed in the table below:
|Table: Aetiology of heart failure (NB: more than one factor may be aetiologically important in an individual)|
|Anatomical category||Aetiology||Examples||Approximate UK prevalence (%)|
||5–10 (NB Hypertension rare as sole aetiology, but history of this in 60% of patients)|
|Endocardial||Valvular heart disease||Aortic stenosis||10|
|Arrhythmia||Atrial fibrillation||Found in 30–40% of heart failure patients, but rarely sole abnormality|
|Congenital heart disease||Ventricular septal defect||<1|
* In the absence of known causes.
There is still debate as to how important it is to determine whether the underlying cause of LV systolic impairment is coronary artery disease or not. Drug treatment may differ for this group of patients from those with dilated cardiomyopathy, e.g. statins and aspirin generally recommended for patients with coronary artery disease, and several trials are examining whether revascularization of patients with heart failure due to coronary artery disease is beneficial. Most centres now recommend noninvasive assessment of the likelihood of coronary artery disease, with stress echocardiography or myocardial perfusion imaging as a preliminary step before coronary angiography is considered.
Acute heart failure
There is no universally agreed definition of acute heart failure, but it is generally considered to represent the relatively abrupt onset of symptoms severe enough to merit hospitalization. It can occur as the first manifestation of a failing heart (acute de novo heart failure), or can occur on the background of chronic heart failure, where the term ‘acute decompensation’ is often applied.
The clinical presentation of acute heart failure varies: perhaps 70% present with peripheral fluid retention, 15% acute pulmonary oedema, 10% hypertensive heart failure, and 5% cardiogenic shock with hypotension and poor organ perfusion. Patients with acute de novo heart failure are more than twice as likely to present with pulmonary oedema or cardiogenic shock than patients with decompensation of chronic heart failure.
Heart failure has a substantial impact on life expectancy. The syndrome is progressive, despite the many therapeutic advances in the past two decades. Mortality remains around 20 to 30% in the first year after diagnosis, reducing to around 10% annually thereafter. Survival is affected by age, the extent of comorbidity, and the severity of the syndrome. The severity of the syndrome is graded by the degree of exertion that causes breathlessness—typically by using the New York Heart Association (NYHA) grading scheme (Table below).
|Table: New York Heart Association classification of symptomatic severity of heart failure|
|I||No limitation: ordinary physical activity does not cause fatigue, breathlessness or palpitations||Asymptomatic|
|II||Slight limitation in physical activity: comfortable at rest but ordinary activity results in fatigue, breathlessness or palpitations||Mild|
|III||Marked limitation of physical activity: comfortable at rest but less than ordinary activity results in fatigue, breathlessness or palpitations||Moderate|
|IV||Unable to carry out any physical activity without discomfort: symptoms of cardiac failure at rest with increased discomfort with any physical activity||Severe|
The mode of death is more likely to be from progressive heart failure in the more severe grades of heart failure (often after several decompensations requiring hospitalization), but sudden death can occur at any time. Predicting likely life expectancy is more difficult than in terminal malignancies, making management decisions more difficult.
The overall in-hospital mortality for patients admitted with heart failure is between 4 and 8%, but for those presenting with cardiogenic shock (low cardiac output with organ hypoperfusion) it is around 40%. Within 12 weeks of initial discharge, 1 in 4 acute heart failure patients are readmitted to hospital and around 15% are dead, rising to 30% at 12 months from discharge.
There are several prognostic scoring systems. The most commonly used is the Heart Failure Survival Score, which takes into account seven variables: aetiology (ischaemic or not), resting heart rate, QRS duration on the ECG, serum sodium concentration, peak oxygen consumption on cardiopulmonary exercise testing, pulse pressure, and LV ejection fraction. This is generally used only in patients in whom transplantation is being considered.
The aims of treatment are to improve life expectancy and to improve quality of life. The relative importance of these aims may differ between patients and may change with time, and the patient’s preferences should be taken into account.
The treatment of heart failure usually involves lifestyle measures and drug therapy. Electrical devices, such as pacemakers and implantable cardioverter defibrillators (ICDs), are being used in an increasing proportion of patients. Surgical intervention—such as valve repair or replacement, LV assist devices, or transplantation—apply only to a minority of patients.
Lifestyle changes can have an important impact on the control of the heart failure syndrome, although few recommendations are supported by a large evidence base.
Fluid restriction is rarely necessary for patients with mild and stable symptoms, but can be useful for those with resistant fluid retention or hyponatraemia. Such patients can be advised to suck ice cubes or suck boiled sweets to assuage thirst, rather than to drink. Salt restriction is generally recommended for anyone with heart failure, with a maximum daily intake of 6 g, but this can be difficult to achieve, particularly if convenience (processed) foods are eaten. Patients with heart failure should avoid ‘low salt’ substitutes as they contain substantial amounts of potassium, which may affect serum levels and the propensity to arrhythmia (unless they are known to be hypokalaemic, perhaps as a consequence of diuretic therapy, and serum potassium concentration is monitored).
Chronic consumption of alcohol, probably at a level of more than 10 units each day for at least 5 years, may lead to heart failure. Abstinence from alcohol in such patients can lead to substantial improvement in LV function and should be recommended. Those affected are likely to require substantial support to achieve this. For those patients in whom alcohol is not thought to be aetiologically important, drinking within currently recommended levels is probably safe, although the fluid load may be important for some patients. Variable alcohol consumption can have a marked affect on anticoagulation control.
Those who continue to smoke are likely to have a worse outcome than those who abstain, although the evidence is not robust. However, smoking has other harmful effects on health and smoking cessation is strongly recommended in all heart failure guidelines. Patients should be provided with the necessary support to achieve this, which is likely to include counselling and nicotine replacement therapy.
Inactivity can lead to physical deconditioning and worsening of exercise intolerance and fatigue. Training can improve exercise performance through adaptation of peripheral muscles, without adversely affecting cardiac function. Both aerobic exercise and resistive exercise are likely to improve symptoms, exercise performance, and quality of life, although compliance with a programme may be difficult and the long-term effects are not known. Many heart failure programmes now offer supervised exercise training along with other elements of rehabilitation therapy. One caveat to a recommendation for regular physical exercise is that swimming may produce rather marked and potentially harmful changes in central haemodynamics: alternative forms of exercise should be encouraged.
Bed rest is still recommended for patients with marked and acute deterioration in the heart failure syndrome (NYHA Class IV), but early mobilization once the syndrome is improving is sensible.
There are no published studies of the effects of sexual activity in patients with heart failure. Breathlessness on exertion and inability to lie flat may clearly interfere with sexual activity, and anxiety about the potential harmful effects may impair enjoyment for both the patient and the partner. Sexual activity increases energy expenditure by a factor of 3 to 5 in healthy men, but with a wide interindividual variation. As a simple guide, if a patient can perform moderate exercise without difficulty, then sexual activity is unlikely to cause a problem. Such issues should be discussed with the patient and their partner. Sildenafil has been used by men with heart failure and erectile problems, but must not be taken with nitrates as this can lead to prolonged hypotension.
There is no convincing evidence of benefit from nutritional supplements in heart failure. For patients with advanced heart failure and cachexia, protein and calorie supplements are frequently prescribed, but the evidence for benefit is scant. Various fruit juices may interact with medication: cranberry juice increases the potency of warfarin, and grapefruit juice interferes with the metabolism of simvastatin. St John’s wort (bought over the counter to treat low mood/depression) may interact with a number of drugs frequently prescribed to heart failure patients, e.g. warfarin, digoxin, eplerenone, and selective serotonin reuptake inhibitors, and the effect of different preparations of St John’s wort can vary markedly.
There are few robust studies of the impact of aromatherapy, reflexology, or relaxation therapy in patients with heart failure. They may improve some aspects of quality of life and may also provide benefit in terms of increased social interaction. There is no evidence of harm.
The provision of psychological therapy by a trained professional—whether education, counselling, stress management, or cognitive behavioural therapy—has not been robustly assessed in heart failure. Anxiety and depression are common and at times may be difficult to distinguish from the heart failure syndrome itself. It is unlikely that psychological therapies would cause harm and they may be a useful starting point before considering drug therapy for psychological or psychiatric disorder. Most guidelines recommend that if drug therapy is to be considered for depression in patients with heart failure, then newer-generation serotonin reuptake inhibitors should be used rather than tricyclic antidepressants.
There are no pathophysiological reasons why most patients with stable heart failure and well-controlled symptoms should not be able to travel by air. Patients with decompensated heart failure, including pulmonary oedema, may become more hypoxic during air travel, as may those who are symptomatic at rest or on minimal exertion. Obviously, if oxygen is needed at rest on the ground, then hypoxia will be worse during air travel. However, for many patients with heart failure the most difficult part of air travel is the long walk within the airport, or the need to stand still and queue for long periods. Assistance may be required to enable easier check-in and transfer to the departure gate.
Patients with chronic cardiac conditions—including heart failure—should receive annual vaccination against influenza. Pneumococcal vaccination is also recommended, and may have to be repeated every 5 years to maintain protection.
Most of the evidence base for the management of heart failure relates to heart failure due to LV systolic dysfunction—‘systolic heart failure’. The best management for heart failure due to valve disease or heart failure with preserved ejection fraction (HFPEF) is less clear.
Diuretics are the most effective means of removing retained fluid, and their introduction often produces rapid symptomatic relief in patients with heart failure, whatever the underlying cause of the cardiac dysfunction. Most patients with heart failure require at least a small dose of regular diuretic. It is common practice to start diuretic therapy at a low dose, and to increase the dose as required to control fluid retention provided renal function does not deteriorate substantially. The dose can often be reduced once an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) has been introduced.
Most patients who require diuretic therapy are treated with a loop diuretic (e.g. furosemide, bumetanide, or torasemide) because these are more powerful than thiazide diuretics. See table below which lists the diuretics that are generally used in heart failure. The combination of a loop diuretic with a potassium-sparing diuretic (e.g. amiloride) can increase diuresis and also guard against hypokalaemia. The risk of hypokalaemia is less if the patient is taking an ACE inhibitor, ARB, or aldosterone antagonist. In the case of resistant fluid retention in severe heart failure, the combination of a loop and thiazide diuretic can be useful. High dose furosemide infusion may also produce a more powerful diuresis than bolus dosing.
|Table: Diuretics used in the treatment of heart failure (based on recommendations from NICE)|
|Drug||Initial dose (mg)||Maximum recommended daily dose (mg)|
a Lower range appropriate for patient on ACE inhibitor or ARB.
NICE CHF guideline.
The minimum dose of diuretic required to control fluid retention should be used: this will vary from one patient to another, and also may vary in an individual patient over time, particularly if there is change in other medication, intercurrent illness, or nonadherence to dietary restriction of salt intake. However, on its own diuretic therapy exacerbates neurohormonal activation and the modern therapy of heart failure due to LV systolic dysfunction demands the use of drugs to antagonize this. An algorithm for treatment is shown below, the NICE recommendations (August 2010).
The main drug classes used are ACE inhibitors, ARBs, β-blockers, and aldosterone blockers such as spironolactone and eplerenone.
ACE inhibitors improve both mortality and morbidity in a wide range of clinical settings, including patients with heart failure due to LV systolic dysfunction, asymptomatic LV systolic dysfunction, and also heart failure or asymptomatic LV systolic dysfunction after myocardial infarction. They should be considered in all such patients. The benefit in chronic heart failure is a reduction in the relative risk of death of 23% and of worsening heart failure of 35%.
Important side effects include cough (perhaps 10% of patients), hypotension, worsening renal dysfunction, and hyperkalaemia. Angio-oedema occurs rarely but requires the immediate withdrawal of the ACE inhibitor. Patients with bilateral renal artery stenosis may suffer a marked and rapid decline in renal function when challenged with an ACE inhibitor (or ARB) and if this occurs the drug should be withdrawn and imaging of the renal arteries considered.
The ACE inhibitor should be started at a low dose and the dose doubled at two weekly intervals with monitoring of blood pressure, renal function and electrolytes, until the target dose is achieved, or failing that the highest tolerated dose below that (see table below). Caution is needed if the patient has significant hyperkalaemia (K+>5 mmol/litre), renal dysfunction (serum creatinine >220 µmol/ litre), symptomatic hypotension or severe asymptomatic hypotension (systolic blood pressure <90 mmHg).
|Table: Drugs used in the treatment of heart failure (as recommended by the Scottish Intercollegiate Guidelines Network)|
|Starting dose||Target dose|
|Captopril||6.25 mg three times daily||50 mg three times daily|
|Enalapril||2.5 mg twice daily||10–20 mg twice daily|
|Lisinopril||2.5–5 mg once daily||20 mg once daily|
|Ramipril||2.5 mg once daily||5 mg twice daily or 10 mg once daily|
|Trandolapril||0.5 mg once daily||4 mg once daily|
|Candesartan||4 or 8 mg once daily||32 mg once daily|
|Valsartan||40 mg twice daily||160 mg twice daily|
|Bisoprolol||1.25 mg once daily||10 mg once daily|
|Carvedilol||3.125 mg twice daily||25–50 mg twice daily|
|Nebivolol||1.25 mg once daily||10 mg once daily|
Adapted with permission from SIGN Guideline 95 - Management of Chronic Heart Failure
The typical cough induced by an ACE inhibitor is unproductive. Other causes should be excluded, in particular lung disease or pulmonary oedema due to worsening heart failure. Many patients can tolerate the cough if it is mild, but if it is bothersome an ARB can be used instead of the ACE inhibitor. If hypotension is a problem, other drugs that lower blood pressure should be discontinued if possible (e.g. nitrates, calcium channel antagonists), and the dose of diuretic can be reduced if there are no symptoms or signs of congestion. If these measures do not help, then the dose of ACE inhibitor may have to be reduced.
Some rise in urea, creatinine, and potassium is usual in patients taking an ACE inhibitor. An increase in K+ to <5.5 mmol/litre is acceptable, but will require continued close monitoring. Potassium-retaining drugs such as spironolactone, eplerenone, amiloride, and triamterene may have to be stopped. Most physicians will accept a rise in creatinine of up to 50 µmol/litre, or to a level of 250 µmol/litre, whichever is the smaller. Nephrotoxic drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs) should be discontinued. The dose of diuretic can be reduced, provided there are no symptoms or signs of congestion.
Serial monitoring of blood biochemistry and blood pressure is essential when introducing and up-titrating an ACE inhibitor (or ARB or β-blocker) in patients with heart failure. Intercurrent illness, particularly if it causes fever or changes in fluid balance, e.g. vomiting or diarrhoea, may have a profound effect on blood pressure and renal function in patients with severe heart failure. This may require cessation of or temporary reduction in the dose of ACE inhibitor, but this should be titrated upwards again once the patient has stabilized.
ARBs block the action of angiotensin at one of its receptor subtypes and thus mimic the effect of ACE inhibitors without producing a rise in bradykinin, hence they do not have the side effect of cough. In other respects their side-effect profile and the actions to take if there are changes in blood pressure or renal function are identical to those for ACE inhibitors.
ARBs proven in randomized trials to reduce the risk of mortality and heart failure deterioration (valsartan and candesartan) are now generally used in patients who cannot tolerate an ACE inhibitor because of cough. This applies to chronic heart failure due to LV systolic dysfunction (candesartan) or heart failure, LV systolic dysfunction, or both after myocardial infarction (valsartan). Candesartan may also be added to therapy with an ACE inhibitor and β-blocker in chronic heart failure, with evidence that this reduces the risk of cardiovascular death or hospitalization for chronic heart failure.
Many randomized clinical trials have shown the benefit of β-blockers in patients with heart failure, with an approximate 25% reduction in the relative risk of death and a 35% reduction in the risk of death from heart failure. This benefit has been seen with a wide range of β-blockers, including bisoprolol, metoprolol, nebivolol (all cardioselective), and carvedilol (non-cardioselective). One caveat to this is that the evidence for metoprolol is strongest for long-acting metoprolol succinate (which is not available in the United Kingdom), rather than the shorter-acting tartrate.
Although providing substantial benefit for patients with heart failure, the introduction of a β-blocker can lead to deterioration in the control of the syndrome. It is therefore important that the β-blocker is introduced at a low dose and titrated up slowly, with close monitoring of blood pressure, heart rate, renal function, and side effects. A β-blocker should not be used in patients with definite asthma, second- or third-degree heart block, or symptomatic hypotension. The cardioselective β-blockers can be used in chronic irreversible airways disease. The starting dose and target dose for the β-blockers proven to be of benefit in heart failure are shown in the table above.
If heart failure worsens on the introduction of a β-blocker—manifest by increasing breathlessness, fatigue, oedema, or weight gain—then the dose of diuretic can be increased, but if this fails to improve the situation the dose of β-blocker should be reduced, but it is rarely necessary to stop the β-blocker completely.
An ECG should be done to exclude heart block if marked bradycardia develops. In the absence of heart block, if symptoms are worsening and the resting heart rate is below 50/min, then the dose of β-blocker can be halved, but again it is rarely necessary to withdraw it. Other rate-slowing medication should be reduced or stopped in preference to reducing the β-blocker dose, e.g. digoxin, amiodarone.
Symptomatic hypotension should trigger the stopping of other blood pressure lowering medications such as nitrates or calcium channel blockers. If there are no symptoms or signs of congestion, the dose of diuretic can be reduced. If these measures are not successful then the dose of β-blocker should be reduced, or in exceptional circumstances it should be stopped. If there is a problem with symptomatic hypotension, most physicians will prefer to have a patient on a medium dose of both an ACE inhibitor (or ARB) and β-blocker, rather than a high dose of only one of these agents.
Two drugs that block the action of aldosterone on its receptor have been shown to be of benefit in heart failure. Spironolactone reduces the risk of death by 30% in patients with moderate to severe heart failure despite treatment with diuretic and ACE inhibitor. This drug, used at a dose of 25–50 mg once a day, can produce gynaecomastia (particularly when digoxin is also prescribed), hyperkalaemia, and renal dysfunction, hence monitoring of renal function and electrolytes is essential, particularly with initiation of therapy or dose adjustment. Changes in fluid balance status can have a marked effect on renal function and serum potassium levels such that frequent monitoring is essential during inter-current illness. Spironolactone should not be used in those with a baseline K+ above 5 mmol/litre or in those with a serum creatinine above 220 µmol/litre, and there is no evidence to support its use in patients with mild heart failure or in the immediate period after myocardial infarction.
Eplerenone is a more selective aldosterone antagonist than spironolactone and therefore much less likely to cause gynaecomastia. It is often prescribed in place of spironolactone if gynaecomastia develops on that drug. The first clinical evidence for its use was obtained in patients with a low ejection fraction (≤ 40%) and either diabetes or heart failure up to 2 weeks after acute myocardial infarction, in whom it reduced the risk of sudden death by 20%, and the risk of death or hospitalization from cardiovascular causes by 13%. More recently (2011) it has been shown to reduce risk of death and risk of hospitalization in patients with mild symptoms (NYHA class II) and systolic dysfunction (ejection fraction <35%). The dose of eplerenone is 25 mg once daily to start, aiming for 50 mg once daily provided renal function and serum potassium concentration are satisfactory. As with spironolactone, it should not generally be prescribed to patients with a baseline K+ of more than 5mmol/litre or serum creatinine above 220 µmol/litre.
Monitoring of renal function and electrolytes should be done frequently after initiation of an aldosterone antagonist (e.g. at 1, 4, 8, 12 weeks) and then every 3 to 6 months thereafter. Changes in the dose of spironolactone or eplerenone (or other heart failure drugs) should trigger a check on renal function and electrolytes, as should any intercurrent illness. NSAIDs should be avoided if at all possible. ‘Low salt’ substitutes, which contain significant potassium, should not be used in cooking. Drugs that increase serum potassium such as amiloride, triamterene, ACE inhibitors, and ARBs should be watched carefully. The combination of ACE inhibitor, ARB, and spironolactone (or eplerenone) is particularly likely to lead to hyperkalaemia and should only be used under specialist supervision. If serum K+ rises above 5.5 mmol/litre (or creatinine to above 220 µmol/litre), then the dose of the aldosterone antagonist should be reduced. If the K+ rises above 6 mmol/litre (or creatinine above 310 µmol/litre) it should be stopped completely. Diarrhoea or vomiting should trigger the temporary stopping of the aldosterone antagonist, which can be reintroduced with appropriate monitoring of renal function and electrolytes once the patient is stable.
There is little evidence that digoxin improves the overall outcome for patients with heart failure in sinus rhythm. It may reduce the risk of worsening heart failure and the need for hospitalization, but it is generally reserved for patients with systolic heart failure who have failed to respond to conventional treatment with diuretic, ACE inhibitor or ARB, β-blocker, and spironolactone.
Digoxin is used to help control ventricular rate in patients with heart failure and fast atrial fibrillation. In this setting a β-blocker is also indicated and likely to have additional benefit. If the combination of a β-blocker and digoxin causes bradycardia, the digoxin should be stopped in preference to the β-blocker.
The usual daily dose of digoxin is 125 to 250 µg if the serum creatinine is normal: in older people and in those with renal dysfunction the dose should be reduced. A number of drugs can alter its pharmacokinetics, the most common problems occurring with antiarrhythmic drugs affecting renal clearance or volume of distribution (verapamil, amiodarone, propafenone, and quinidine), drugs increasing its absorption (erythromycin, omeprazole, tetracycline), and drugs decreasing its absorption (colestipol, cholestyramine). A more complete list can be found in the British National Formulary (http://bnf.org).
Digoxin has a narrow therapeutic window, with arrhythmia and gastrointestinal side effects being the most common clinical reasons for withdrawal. There is little relationship between the serum level of digoxin and its therapeutic effect, but measurement of the serum level may be useful to confirm compliance or the clinical suspicion of toxicity. It is important to realize that toxicity can occur even with ‘normal’ serum levels, and is likely to be worse when serum potassium concentration is deranged.
Amiodarone is effective against most ventricular arrhythmia but does not improve the overall mortality in patients with heart failure at risk of sudden death. It can be used to try and cardiovert atrial fibrillation back to sinus rhythm, and to reduce the need for DC shocks in patients with recurrent ventricular arrhythmia and an ICD.
Amiodarone has numerous side effects, including photosensitivity, thyroid dysfunction, pulmonary fibrosis, liver dysfunction, and neuropathy. Corneal microdeposits are common but rarely necessitate stopping the drug. The need to continue its prescription should be reviewed regularly, with regular monitoring of thyroid and liver function, and a careful watch for signs of pulmonary toxicity.
This combination was shown to reduce mortality in heart failure in the pre-ACE inhibitor era, but is less effective than ACE inhibitors. In African-American patients the combination appears to reduce the risk of death or hospitalization from heart failure in patients with moderate to severe symptoms and on top of treatment with diuretic, ACE inhibitor or ARB, and β-blocker. In white patients the combination of nitrates and hydralazine is reserved those intolerant of an ACE inhibitor or ARB because of renal dysfunction or hyperkalaemia. When used at the correct dosage, vasodilator side effects are common, and rarely hydralazine can induce a lupus-like syndrome.
In randomized trials, statins have had a neutral effect on outcome in patients with heart failure, whether ischaemic or non-ischaemic in aetiology. n-3 polyunsaturated fatty acid supplementation of 1g/day reduced mortality by 9% in one randomized trial.
Warfarin should be prescribed for patients with heart failure and atrial fibrillation (whether paroxysmal or persistent) as it reduces the risk of thromboembolism including stroke. In those in whom the risk of warfarin is considered too high, aspirin at the dose of 300 mg daily can be considered, but is likely to be less effective than warfarin at preventing thromboembolism.
In sinus rhythm the balance of risk and benefit is more difficult, but warfarin should be considered for those with intracardiac thrombus, LV aneurysm, or a history of thromboembolism.
Many patients with heart failure have coexisting atherosclerotic disease and are likely to be on long-term aspirin therapy. There is some debate as to the potential harmful effects of this agent in chronic heart failure, with some evidence that it may increase the risk of decompensation. Most physicians use aspirin at a dose of 75 mg once daily for patients with coexisting symptomatic atherosclerosis (e.g. previous myocardial infarction, angina, stroke, or transient ischaemic attack).
Calcium channel blockers do not improve the outcome in patients with heart failure. Amlodipine and felodipine (long-acting dihydropyridines) are not harmful and may be useful in patients with concomitant angina, although β-blockers should be considered first. Verapamil, diltiazem, and short-acting dihydropyridines (e.g. nifedipine) can cause clinical deterioration and should not be used.
Drugs used in acute decompensation, including inotropes
Most patients hospitalized with heart failure have had a previous diagnosis of the condition and are already on disease-modifying therapy e.g. with ACE inhibitors, ARBs, and/or β-blockers. The treatment of acute decompensation of chronic heart failure depends on the clinical status of the patient. The table below shows a practical approach, classifying patients depending on their fluid status (‘wet’ or ‘dry’) and organ perfusion (‘warm’ or ‘cold’). If the patient is warm but wet, then intravenous diuretic therapy and vasodilators such as intravenous nitroglycerine can be used. If the patient is cold and dry, then careful intravenous fluid replacement should be tried, under close monitoring. If this fails to increase organ perfusion then inotropic agents can be used, which are also first line for the cold and wet patient. Inotropic agents increase cardiac output and organ perfusion and may dramatically improve the clinical condition of the patient, reducing pulmonary wedge pressure, clearing pulmonary oedema, and allowing a diuresis as renal perfusion improves.
|Table: Simple clinical classification and approach to treatment of the patient with acute heart failure|
|Congestion Perfusion||Not present: patient is ‘dry’||Present: patient is ‘wet’|
|Good: patient is ‘warm’||Well compensated—alteration in management is probably not required (good prognosis)||Diuretics ± vasodilators|
|Poor: patient is ‘cold’||May be over-diuresed: careful fluid replacement ± inotropes||Inotropes ± diuretics (poorest prognosis)|
The inotropic agent most often used is dobutamine, although the evidence base is weak. It acts on β-adrenoreceptors and may therefore be less effective in patients on β-blockers, in which case the phosphodiesterase inhibitors (such as milrinone or enxoimone) may be more effective. Dobutamine may induce sinus tachycardia and more serious cardiac arrhythmia, may exacerbate myocardial ischaemia due to increased myocardial oxygen consumption, and may lose effect with prolonged treatment (‘tachyphylaxis’). The phosphodiesterase inhibitors cause vasodilatation in addition to increasing myocardial contractility, which may be useful, but they also increase myocardial oxygen consumption and can induce arrhythmia. Excessive peripheral vasodilatation may exacerbate hypotension.
Levosimendan is a newer inotropic agent with vasodilator properties, not yet available in the United Kingdom, but may be better tolerated and slightly more effective than dobutamine. Nesiritide (synthetic human B-type natriuretic peptide) is used in North America as a powerful vasodilator with some natriuretic effect, although there is some concern about a possible harmful effect on renal function in some patients.
Chronic therapy with oral inotropes (such as the phosphodiesterase inhibitors) is not used because it increases mortality.
Drugs in development
Other therapies have been tried but found to be unhelpful or harmful include antitumour necrosis factor, endothelin antagonists, minoxidil, and rolofylline (an adenosine A1-receptor antagonist). A large number of other drugs are in development.
Drugs to avoid or use with caution
Patients with heart failure may have significant renal (and hepatic) impairment. Drugs cleared predominantly by the kidney (and liver) can therefore accumulate in these patients, causing toxicity, and this can include drugs used to treat heart failure itself such as ACE inhibitors and digoxin.
NSAIDs may exacerbate fluid retention and renal dysfunction in patients with heart failure and should be used with caution. This applies to both nonselective agents and the newer COX-2 selective agents. Oral and intravenous steroids may also exacerbate fluid retention.
Drugs with a negative inotropic effect should also be avoided, including verapamil, dilitazem and Class I antiarrhythmic agents. Other drugs to be avoided include glitazones (fluid retention), metformin (lacticacidosis in severe heart failure), tricyclic antidepressants (arrhythmia and reduced contractility), carbenoxolone (fluid retention), macrodlide antibiotics, and some antifungal agents (QT prolongation and increased risk of arrhythmia). Fuller details can be found in the British National Formulary (http://bnf.org).
Nonprescription drugs (such as herbal remedies) can have important interactions with prescription drugs taken by patients with heart failure. St John’s wort can affect serum levels of digoxin and warfarin. Liquorice and dandelion can lead to fluid retention. Ginko, garlic, aescin and dong quai can increase the risk of bleeding. More details can be found on the website http://herbmed.org.
Comorbidity and its impact on drug therapy
The average age of a new patient with heart failure in the UK is 75 years, hence comorbidity is common. This may complicate management and increase the risk of adverse events with ‘standard’ therapy.
Most patients with heart failure will have at least mild derangement of renal function, which can be worsened by excessive diuresis, hypotension, or the use of ACE inhibitors/ARBs and aldosterone antagonists. The serum creatinine can appear relatively normal, despite marked impairment of renal function, because of old age and low muscle bulk, and estimated glomerular filtration rate (eGFR) should always be considered.
β-Blockers are absolutely contraindicated in asthma, but in chronic airways disease where there may be little reversibility a cardioselective β-blocker (such as bisoprolol or nebivolol) should be tried under careful supervision.
β-Blockers are the drugs of choice for concomitant angina. Nitrates (both sublingual and oral) are safe to use in heart failure, provided blood pressure is satisfactory. Only long-acting dihydropyridine calcium antagonists (such as amlodipine) can be safely used in heart failure: nifedipine, diltiazem, and verapamil should not be used. Revascularization may have to be considered if patients remain symptomatic from angina.
Paroxysmal or persistent atrial fibrillation affects 30 to 40% of patients with heart failure and the best management for this is unclear, excepting that they require anticoagulation with a target INR of 2.5. Most physicians will attempt to restore sinus rhythm at least once unless the ventricular function is so poor or the atrial size so large that the chances of success are deemed too low. The usual approach is to attempt chemical cardioversion with oral amiodarone, and if this fails after 4–6 weeks to perform a DC cardioversion. The amiodarone is continued for some months but can usually be stopped if sinus rhythm is maintained for 6 months or more. If the chance of cardioversion is deemed low, or cardioversion has failed before, then the aim is to control the ventricular rate, usually with a combination of β-blocker and digoxin. In some patients this is difficult and atrioventricular nodal ablation with permanent pacing (perhaps with a biventricular rather than right ventricular system) is necessary to control a high resting ventricular rate. The role of atrial ablation in patients with heart failure is unclear: success in routine practice in the typical patient with much structural heart damage is likely to be low, but trials are under way.
Many patients with heart failure are anaemic, some due to iron deficiency from blood loss from the gastrointestinal tract or poor dietary intake, but many due to concomitant renal dysfunction or the heart failure syndrome itself. Those with anaemia have a worse prognosis than those without, but there is no convincing evidence that treatment with a combination of erythropoietin and intravenous iron improves mortality. Most physicians will treat anaemia with these drugs in patients with heart failure and moderate to severe renal dysfunction while the results of large randomized controlled trials are awaited, and it seems sensible practice to correct severe anaemia with blood transfusion (slowly, with diuretic cover and close clinical supervision) in patients admitted to hospital with exacerbation of heart failure.
Gout is not uncommon in patients with heart failure, particularly those who require high dose diuretics to control fluid retention. NSAIDs should be avoided because they worsen renal function and the tendency to fluid retention. Most physicians treat acute attacks with colchicine, adding in allopurinol when the attack has settled in an attempt to reduce the risk of a subsequent attack. Occasionally a short course of oral steroid is needed to abort the attack, but this can lead to fluid retention.
Treatment of heart failure with preserved ejection fraction
Most of the evidence base relating to the drug treatment of heart failure has come from trials with patients with obvious impairment of LV systolic function. Many patients, particularly elderly people with a history of hypertension and/or diabetes, do not have systolic dysfunction but a presumed abnormality of diastole—termed ‘diastolic’ or heart failure with preserved ejection fraction. This is most usually a diagnosis of exclusion and the physician should check that there is not another (noncardiac) explanation for symptoms. An elevated plasma BNP concentration, in the absence of marked renal dysfunction, helps confirm the diagnosis.
If the diagnosis of nonsystolic heart failure is secure, then the patient requires treatment. This will include a diuretic, at as low a dose as possible to control fluid retention because high doses are tolerated poorly, with the stiff ventricle requiring adequate filling pressure to maintain its output. Concomitant atrial fibrillation needs treatment in its own right because patients with stiff ventricles tend to tolerate this arrhythmia particularly poorly.
There is little direct evidence for the use of ACE inhibitors in this condition, although theoretically they should be helpful. There is some, not very robust, evidence that the ARB candesartan can reduce the risk of cardiovascular mortality or heart failure hospitalization in patients with non-systolic heart failure, but a large randomized trial of irbesartan found no such effect. β-Blockers and rate-limiting calcium antagonists (such as diltiazem or verapamil) are used to increase the filling time of the ventricular cycle, but there is little hard evidence to prove that this is clinically useful.
Comorbidites such as obesity, hypertension, and diabetes should be treated on their own merits.
Devices used to treat heart failure
Permanent pacing has been used to treat symptomatic bradycardia in patients with heart failure for many years. It may alleviate heart failure when this is associated with complete heart block.
Dual chamber (atrio-right ventricular) pacing for the treatment of heart failure in the absence of symptomatic bradycardia or heart block produces no haemodynamic benefit and may have a detrimental effect on LV function. This is probably due to the fact that right ventricular apical pacing results in a left bundle branch block pattern of ventricular activation that induces ‘mechanical dyssynchrony’, with regions of early and late contraction: the interventricular septum contracts early relative to the delayed contraction of the LV lateral free wall. In its most severe form such dyssynchrony can result in contraction of the septum whilst the lateral wall is still relaxing and vice versa. With failure of opposing ventricular walls to contract together, a significant amount of blood is simply shifted within the ventricular cavity instead of being ejected into the circulation, thereby reducing cardiac output. The proportion of the cardiac cycle available for LV filling and ejection is also reduced by dyssynchronous contraction, leading to a further decrease in the pumping ability of the heart.
Patients with mechanical dyssynchrony due to native left bundle branch block (perhaps up to 20% of all heart failure patients) are increasingly likely to be considered for sophisticated pacing using an atriobiventricular system to reduce the dyssynchrony (cardiac resynchronization therapy, CRT). With this therapy the conventional right atrial and right ventricular pacing wires are supplemented by a third lead placed in a lateral coronary vein via the coronary sinus, thus allowing pacing of the left ventricle transvenously. This can lead to an improvement in LV systolic function, reduction in ventricular dimensions, increase in LV filling time, reduction in pulmonary capillary wedge pressure, and increase in cardiac output and systemic blood pressure. Large clinical trials have demonstrated a substantial reduction in mortality (up to 40%) in patients with left bundle branch block and moderate to severe symptoms of heart failure despite optimal drug therapy. Symptoms, the risk of rehospitalization, and quality of life also improve. A few patients, however, do not respond to this therapy: work is ongoing to determine the best way of identifying these. It is still not clear if patients with atrial fibrillation benefit as much as those in sinus rhythm. Recent trials also suggest there may be a role for CRT in some patients with milder symptoms, e.g. those with NYHA class I or II symptoms, but with a low ejection fraction (30% or less) and a wide (>130 msec) QRS complex.
ICD therapy reduces mortality in patients with coronary artery disease, impaired LV systolic function, and failed sudden death or evidence of ventricular arrhythmias, when compared to optimal medical therapy alone. Patients with coronary artery disease, very poor LV systolic function (ejection fraction <30%), and a broad QRS complex (>120 ms) are also identified as a group at high risk of sudden death, and ICD implantation is recommended, even in the absence of documented ventricular arrhythmia—but not within 4 weeks of an acute myocardial infarction. Patients with severely symptomatic heart failure (NYHA Class IV) are generally not considered suitable for such therapy: the risk of death is substantially greater from progressive heart failure, and a sudden death in these circumstances may not be the worst outcome.Implantable cardioverter defibrillator (ICD) therapy
The evidence for the use of ICDs in patients with heart failure not due to coronary artery disease is less robust, but at least one large trial suggests that an ICD benefits these patients as much as those with coronary artery disease. Amiodarone appeared to be no better than placebo in terms of reduction in mortality in heart failure patients, although it suppresses ventricular arrhythmia and may reduce the frequency of (appropriate) shocks in patients with ICDs.
Combined therapy with CRT and ICD (CRT-D)
It is possible to combine CRT with an ICD in one device. Such an approach is likely to maximize the impact on reducing mortality in patients with heart failure. Opinion differs as to which patients should be considered for combined therapy, but increasingly if a CRT device is being fitted, the physician will opt for the more expensive CRT-D system to provide greater protection against sudden death.
LV assist devices
The worldwide experience of using implantable ventricular assist devices is steadily increasing, with a small number of patients continuing on such mechanical support for more than 2 years. Although accepted as an appropriate ‘bridge to transplant’ for patients deteriorating while on a cardiac transplantation waiting list, the role of these devices as ‘destination therapy’ is unclear. There is evidence that in some patients the heart may recover whilst being supported by such devices, but how best to identify such patients and how to stimulate the heart to recover is as yet unclear. The use of such devices outside the context of a heart transplantation programme is not recommended.
Other interventions for heart failure
Heart failure due to primary valve disease is potentially curable. It is thus vital that this is detected. Good clinical examination supplemented by a high-quality Doppler echocardiogram is essential. The timing of valve replacement can be difficult and is based on the cardiac anatomy, severity of the disease, comorbidities, ventricular function, haemodynamics, and rate of progression of the valve disease. Rapid deterioration suggests the possibility of a change in cardiac rhythm (e.g. onset of atrial fibrillation) or infection (endocarditis) and requires specialist input.
Severe aortic stenosis may present in elderly people with heart failure. The risk of valve replacement is often considered too high, but recent developments in percutaneous valve replacement may offer a new therapeutic avenue. An expandable stented valve is placed percutaneously through the orifice of the native aortic valve, and is then expanded under considerable pressure. The ‘new’ valve then operates as a better conduit for blood from the left ventricle, with a reduction in afterload. The procedure is being performed in more specialist cardiac centres, but is still in development.
A similar procedure can be used for percutaneous pulmonary valve replacement in patients with congenital heart disease. Percutanous mitral valve repair for patients with moderate to severe functional mitral regurgitation is at an earlier stage of development, and relies upon percutaneous access to the coronary sinus.
Although ischaemic heart disease is the most common cause of heart failure in the United Kingdom and other developed countries, the benefits of revascularization in chronic heart failure are not well established. The risk of coronary artery bypass surgery in patients with poor LV systolic function can be high, and many surgeons are reluctant to take on such candidates despite evidence from some studies that they have the most to gain from surgery.
There is considerable heterogeneity in the effect of coronary artery disease on the LV myocardium in such patients, with regional variation in the extent of scar, viable but noncontractile (‘hibernating’) tissue, and viable and contracting (‘normal’) tissue. A variety of imaging techniques can be used to try to determine the extent of such hibernation, including stress echocardiography, nuclear imaging, and cardiac MRI. Several randomized trials are examining whether revascularizing those with significant hibernating myocardium is beneficial.
For those with symptoms of angina or breathlessness due to inducible ischaemia, revascularization for symptom improvement is generally considered reasonable after optimization of medical treatment if the coronary anatomy is suitable.
The number of heart transplantations performed worldwide has been falling for the past decade. This relates to both a reduction in the supply of organs and better drug therapies for patients with heart failure. There are no randomized studies of transplantation, but case series suggest benefit in those with severe heart failure, no significant comorbidity, and an expected survival of less than 70% at 5 years.
Other surgical procedures
Patients with severe LV dilatation often have severe ‘functional’ mitral regurgitation sue to stretching of the valve ring. Surgical correction of the regurgitation is possible, but more data are needed before those most likely to benefit can be clearly identified.
Ventricular reduction surgery—particularly where an area of scar tissue can be removed—may be of benefit in selected patients with heart failure. Use of this in patients with globally dilated left ventricles and little regional variation in the extent of scar is not currently recommended.
Cardiomyoplasty, a procedure where skeletal muscle is wrapped around the ventricle and ‘trained’ to contract more like cardiac muscle, has been examined, but remains an experimental technique with considerable technical challenge.
Ultrafiltration can be used to treat hospitalized patients with resistant fluid retention or pulmonary oedema. Smaller bedside devices that can be managed on a coronary care unit have been developed, but experience to date is limited.
Sleep-disordered breathing is found in 50% of patients with heart failure, with central sleep apnoea predominating in more severe heart failure. Cheyne–Stokes respiration is a particular type of central sleep apnoea. Obstructive sleep apnoea can, and should be, treated with continuous positive airways pressure (CPAP), which can now be safely and easily organized in a patient’s home. There is as yet no evidence that treating central sleep apnoea with CPAP or servoassisted ventilation improves outcome, but a large randomized trial is under way.
Patients presenting with acute pulmonary oedema may benefit from CPAP therapy or other forms of assisted ventilation, particularly if the work of breathing is consuming a large proportion of the limited cardiac output. This should be considered in consultation with the intensive care unit staff.
Disease monitoring and communication with patient and carer
Traditionally patients with heart failure have been assessed periodically in primary or secondary care by clinical examination (noting the extent of fluid retention, jugular venous pressure, and lung auscultatory findings) supplemented by checking of blood biochemistry. Recent randomized studies have suggested that serial monitoring of plasma BNP and adjustment of therapy to reach a target level of BNP may improve the clinical outcome compared with standard care, but this is not as yet routine.
The box below some of the subjects to discuss with a heart failure patient and their family. Clearly, not all of these topics can be covered in one consultation, and written or visual material can be very helpful in reinforcing key information and self-management. Experienced heart failure physician and nurse teams reliably reduce hospitalization rates in patients with heart failure, the key element probably being close contact between the nurse and the patient/carer, enabling early identification of clinical deterioration. Patients can monitor their weight and be educated to adjust their diuretic dose at an early stage of decompensation
Box: Subjects to discuss with a patient with heart failure and their family and carers
- ◆ What is heart failure?
- ◆ Why do symptoms occur?
- ◆ How to recognize symptoms?
- ◆ What to do if symptoms worsen
- ◆ Self-weighing
- ◆ Rationale for treatments
- ◆ Importance of adherence to lifestyle and drug therapy
- ◆ Smoking cessation
- ◆ Anxiety and depression
- ◆ Prognosis
- ◆ Dietary restrictions, including salt, fluid, and alcohol
- ◆ Rest and exercise
- ◆ Sexual activity
- ◆ Travel
- ◆ Drug effects
- ◆ Dose and timing
- ◆ Adverse effects
- ◆ Self-management (particularly diuretic dose)
- ◆ Vaccination
Telemonitoring (generation of clinically relevant data that are transmitted remotely to a health care professional) has been examined in a number of randomized trials. Although the details differ markedly from one telemonitoring system to another, the evidence suggests that such an approach is safe and acceptable to patients and their families, and although not necessarily reducing hospitalizations it does reduce mortality. This is presumably due to better compliance with drug therapy and earlier identification of decompensation.
Modern generations of CRT and ICDs can also provide information useful for chronic disease monitoring in heart failure, e.g. frequency and duration of episodes of atrial fibrillation, heart rate variability (reflecting sympathetic tone in the autonomic nervous system), patient activity, and even intrathoracic impedance or indirectly estimated pulmonary artery pressure. It is likely that such data could be used by health care professionals to better manage patients with these devices, although this area is in its infancy.
‘Heart failure’ has strongly negative connotations for lay people, who equate it with ‘cardiac arrest’. Feedback from patient and carer focus groups suggests that an early and frank discussion of the diagnosis and treatment options is greatly appreciated. Such discussion will also improve the patient’s understanding of the disease and empower them (and their carer) to take more of an active role in management. Health care professionals should be sensitive to the information needs of their patients and tailor the method and content of their communications appropriately. The detection of anxiety and depression is important, particularly as these are common in patients with heart failure: counselling, cognitive behavioural therapy, and (if necessary) drug therapy are likely to improve quality of life.
End of life issues
Palliative care skills are an important component of good management of heart failure, particularly in the terminal stages of the condition. Good communication between the health care professionals (in primary and secondary care) and the patient and family is particularly crucial at this point. General palliative care can be given by the heart failure team, working with the primary care services. More specialist input may be necessary at times. Local arrangements vary markedly. Key issues are symptom management, decision making, withdrawal of unnecessary or inappropriate therapies (including drugs and defibrillation), emotional support, and coordination of care. Patient preferences may change over time.