Success in heart failure – new evidence, new approaches

The availability of new pharmacological options – together with the increased risk of heart failure associated with both COVID-19 infection and the impact of the pandemic on health care – have put heart failure high on the agenda for the coming year

Heart failure management is firmly back on the map for general practice in 2021. Although there are Quality Outcomes Framework (QOF) points available for carrying out heart failure reviews, the pandemic has meant that people have had less contact with their healthcare team, and they may be at increased risk of developing heart failure because their risk factors may have been less well managed. There is also an increased interest in new evidence relating to the management of heart failure with reduced ejection fraction.

In this article, we aim to give an overview of the diagnosis and management of heart failure. By the end of the article you should be able to:

• Recognise the pathophysiology of heart failure
• Identify different types of heart failure
• Consider risk factors
• Evaluate diagnostic pathways
• Analyse the management of heart failure, including new pharmacological options that are available

THE PATHOPHYSIOLOGY OF HEART FAILURE

Heart failure is a term that describes the failure of the heart to meet the circulatory needs of the body.¹ Many lay people will confuse heart failure with a heart attack, but although there is a link between the two conditions, they are very different. In heart failure, the heart fails to pump out an adequate supply of blood to the body, either because the left ventricle, the main pumping chamber, is underperforming, or because the heart fails to fill with blood during diastole.² As a result, the kidneys and pressure receptors around the body recognise that the pressure is dropping and so instigate a ‘rescue plan’ to conserve the circulation and keep fluid volumes and salt levels up so that the pressure is maintained. These rescue mechanisms are based within the renin angiotensin aldosterone system (RAAS) and the sympathetic nervous system (SNS).² However, activation of these systems and the subsequent vasoconstriction and fluid overload puts extra pressure on the struggling heart. Much of heart failure management focuses on downregulating these systems in order to take pressure off the heart.

CLASSIFICATION OF HEART FAILURE

As indicated above, there are different types of heart failure and over the years there have been various names given to the different types. Recently, however, the aim has been to simplify the classification of heart failure into two main categories:

1. Heart failure with reduced ejection fraction (HFrEF), and

2. Heart failure with preserved ejection fraction (HFpEF).

A third category is known as heart failure with mid-range ejection (HFmrEF) and this can progress to either HFrEF or HFpEF.³

The ejection fraction is defined as the amount of blood pumped out from the left ventricle in the systolic phase of the heart’s cycle.⁴ A recent update to the British Society of Echocardiography’s guidance describes a normal left ventricular ejection fraction as being 55% or above.⁵ However, other countries vary in their definitions. The European Society of Cardiology states that HFrEF would be diagnosed if the left ventricular ejection fraction (LVEF) is less than 40%, with a value of 50% or more being normal.³ Many heart failure trials only include people with a reduced LVEF of 40% or less.

In HFpEF, as the name suggests, the ejection fraction is normal. People with HFpEF may have symptoms and markers for a heart failure diagnosis, but the LVEF is preserved.³ This type of heart failure may have been referred to as diastolic heart failure in the past because the problem relates to the heart’s inability to fill effectively in the diastolic phase of the cycle.

RISK FACTORS

Commonly recognised risk factors for heart failure include:

• History of myocardial infarction
• Hypertension
• Atrial fibrillation, and
• Thyroid disorders.¹

Heart failure has been noted to be one of the earliest and most deadly complications of type 2 diabetes.⁶

The pandemic means that some of these risk factors could be missed and guidance from the Oxford Academic Health Science Network, published via the Primary Care Cardiovascular Society, has highlighted this problem.⁷ The document includes advice for making the most of every face to face contact in order to diagnose and manage cardiovascular risk factors. It also includes strategies for improving self-management in people with, or at risk of cardiovascular disease through, for example, home blood pressure monitoring or pulse checks.

Furthermore, and worryingly, recent data suggest that coronavirus can also affect the cardiovascular system, leading to complications such as acute myocardial infarction, heart failure, and dysrhythmias.⁸ This suggests that healthcare professionals will be seeing the fall out of COVID-19 long after the pandemic is over.

THE DIAGNOSIS OF HEART FAILURE

The symptoms of heart failure can be quite generic, with breathlessness, oedema and fatigue being the most common presentations.¹ On that basis, it is important to take a careful history in anyone complaining of these symptoms, recognising risk factors for a heart failure diagnosis. History-taking is a vital part of the diagnostic pathway for most conditions and even a remote consultation offers the opportunity to take a thorough history by listening to the patient’s story and using the medical notes to back up and augment that history.

Signs may include a raised jugular venous pressure, lung crackles or a third heart sound. Clinical examination and objective tests to confirm the presence of heart failure will normally require a face to face assessment.

ECGs should be part of the diagnostic pathway, according to NICE. NICE has offered guidance on the use of remote ECG recordings in atrial fibrillation,9 and the European Society of Cardiology (ESC) has validated their use,10 suggesting that they may also be useful in identifying abnormalities in suspected heart failure.

Other tests that may be considered, both to underpin the diagnosis of heart failure and to identify other conditions that may present similarly include a chest X-ray, a full blood count and tests for renal, liver and thyroid function, lipids, HbA1c, and lung function tests (peak flow or possibly spirometry, depending on local guidance).¹

The NT-pro-BNP blood test is an important ‘rule out’ test for heart failure, in that if it is normal (<400 pg/ml) a diagnosis of heart failure can usually be discounted. Conversely, a very high reading (>2000 pg/ml) would indicate the need for early assessment with an echocardiogram.¹

Echocardiography is deemed to be the gold standard test for heart failure as it can measure the ejection fraction and can also assess the heart’s structure and function.¹

MANAGEMENT

The management of heart failure should include the diagnosis and treatment of any correctable causes such as thyroid disorders, and optimisation of the treatment of any comorbidities such as chronic obstructive pulmonary disease (COPD), hypertension or diabetes.

As indicated earlier, much of the pharmacological management of heart failure will focus on downregulating the two systems which are inappropriately responding to the drop in pressure caused by the inability of the heart to pump effectively. RAAS activity can be moderated through the use of ACE inhibitors (ACEi) as identified in studies such as CONSENSUS or SOLVD, which showed ACEi-related improvements in morbidity and mortality.^11,12 Angiotensin receptor blockers (ARBs) such as candesartan, have also been shown to offer these benefits.¹³ Dose optimisation will achieve the best outcomes.

The activity of the sympathetic nervous system can also be reduced through the use of beta blockers, such as bisoprolol, carvedilol, metoprolol and nebivolol.¹⁴ Studies have confirmed that the use of beta blockers alongside drugs which act on the RAAS, also improves morbidity and mortality, although the advice to ‘start low, go slow’ should always apply to initiating and uptitrating this class of medication: around one in three people will find their symptoms deteriorate after starting or increasing the dose of a beta blocker.

Mineralocorticoid receptor antagonists (MRAs) such as spironolactone or eplerenone have also shown evidence of benefit in people with heart failure, irrespective of symptoms. However, NICE reserves these drugs for people who remain symptomatic on ACE inhibitors and beta blockers.¹

Diuretics, such as furosemide, bumetanide and metolazone are used mainly for the relief of symptoms linked to fluid retention but do not offer mortality benefits. It is also important to remember that when people with heart failure are effectively treated with ACE inhibitors or ARBs and beta blockers, they may not need a diuretic every day. Inappropriate use is associated with adverse effects and hospital admissions, so diuretic therapy needs to be managed with care.¹⁵

Other therapies

Other therapies that are sometimes used in heart failure include ivabradine and the angiotensin receptor neprilysin inhibitor (ARNI) sacubitril/valsartan. Ivabradine can be used as an alternative, or in addition, to a beta blocker, on the basis of trial data which showed that ivabradine can prevent HF-related death and hospitalisation, and can also improve quality of life, in symptomatic patients with LVEF ≤ 35%, who were in sinus rhythm and had a resting heart rate of 70 or above.¹⁶

The 2018 NICE guidelines on heart failure refer to the use of the first available ARNI on the market, sacubitril/valsartan.¹ The PARADIGM-HF trial comparing sacubitril/valsartan with placebo, demonstrated early mortality benefit which was sustained throughout treatment, and the trial was stopped early as a result. Early initiation of sacubitril/valsartan could therefore be considered,17 although NICE recommends that it should be a ‘specialist only-initiated drug’. A specialist is defined by NICE as ‘most likely to be a cardiology consultant’, although the phrase is open to interpretation. Closer working between primary and secondary care may help to facilitate earlier use of sacubitril/valsartan in appropriate patients.

SGLT2 inhibitors

Much more recently, there has been a great deal of interest in the role of sodium glucose co-transporter inhibitors (SGLT2i) in heart failure. Cardiovascular outcome trials (CVOTs) carried out in people with diabetes demonstrated unexpected benefits in terms of reductions in hospitalisations for heart failure (hHF). These findings led to further trials being carried out, aimed specifically at heart failure outcomes.

The first of these, DAPA-HF, looked at cardiovascular death rates and worsening heart failure in people with a LVEF of 40% or less, in people taking dapagliflozin on top of usual standard of care. The results showed that the primary outcome occurred in 16.3% of patients in the dapagliflozin treated group and in 21.2% in the placebo group. A first worsening heart failure event occurred in 10% in the dapagliflozin group and in 13.7% of the placebo group. Death from cardiovascular causes occurred in 9.6% of people in the dapagliflozin group and in 11.5% of people in the placebo group and 11.6% versus 13.9% died from any cause. Furthermore, treatment with dapagliflozin improved symptoms, physical function, health status and quality of life in patients with HFrEF, on top of the benefits offered by standard heart failure management.¹⁸

Subsequently the EMPEROR-Reduced trial showed that patients treated with empagliflozin had a lower risk of cardiovascular death or hospitalisation for heart failure than those in the placebo group.¹⁹ During the trial, a primary outcome event occurred in 19.4% of patients in the empagliflozin treated group and in 24.7% in the placebo group. Excitingly, these trials showed that the benefits of the two SGLT2i drugs extended to people with and without diabetes.

As a result of this evidence, and based on the patient’s signs and symptoms, the standard treatment of heart failure should include:

• An optimised ACE inhibitor
• An optimised beta blocker, and
• A carefully titrated diuretic.

Additionally, consideration should be given to including an SGLT2i. The SGLT2i dapagliflozin has just been approved by the European Medicines Agency for use in HFrEF in people with and without diabetes, and is now indicated in the UK for the treatment of symptomatic chronic HFrEF.

There are various mechanisms which are thought to lead to the improvements seen in people with (and at risk of) heart failure who take SGLT2 inhibitors. These include stimulation of natriuresis and diuresis, effects on the cardiac myocytes, improvements in diastolic and systolic function, improved endothelial function and inhibition of cardiac fibrosis.²⁰

It is important to remember that the evidence base for pharmacological interventions rests with HFrEF. So far, the search for drugs which are effective in HFpEF has been much less fruitful.²¹ Sowden et al22 recently identified concerns with how HFpEF has become the Cinderella of heart failure syndromes. The authors stated in their conclusion that the profile of HFpEF needs to be raised, particularly with respect to how it can be better managed through interventions such as cardiac rehabilitation.²² Trials examining the effect of SGLT2 inhibitors for HFpEF are ongoing.

LIFESTYLE INTERVENTIONS

As well as pharmacological therapies, lifestyle interventions can have a positive effect on heart failure outcomes.¹ People with a diagnosis of heart failure should be advised to eat healthily, stop smoking, keep alcohol intake within government recommendations and to remain physically active. People should be reminded that although breathlessness may feel uncomfortable, it is not doing any harm and so physical exercise should be encouraged. In recent years, people with heart failure have been welcome at cardiac rehabilitation programmes, based on evidence that shows that cardiac rehabilitation can extend and improve quality of life for people with heart failure.²³ As a result of the disease process and the drugs used to manage heart failure, sodium reduction should be encouraged. Advice should be given about the importance of hidden salts in foods, as well as the risks of adding salt when cooking or at the table.¹ Fluid restriction is rarely required in heart failure patients.

THE ANNUAL REVIEW IN PRIMARY CARE

When reviewing an individual with heart failure, it is essential to understand the rationale behind the boxes that need to be ticked. For example, the New York Heart Association classification system relates to how symptomatic the patient is. As symptoms can vary over a period of time, so can the person’s classification score. In COPD, people can have a modified MRC score which is at odds with their lung function. Similarly in heart failure, people’s NYHA score may not directly align with their ejection fraction. Both elements (EF and NYHA) should be used to guide management of heart failure.

Functional status, beyond the NYHA score, should also be assessed. Poor functional status (i.e. the ability to perform activities of daily living [ADL]) is also associated with poor outcomes including the likelihood of needing hospitalisation and increased risk of dying.²⁴

DEVICE THERAPY IN HEART FAILURE

Cardiac resynchronisation therapy (CRT) and implantable cardiac devices (ICDs) can have a significant impact on people with heart failure, albeit they will need to meet the criteria for each. CRT therapy enables biventricular electrical impulses to synchronise the heartbeat and improve ventricular function, resulting in improved outcomes.²⁵

People with heart failure are at increased risk of fatal arrhythmias so ICDs can help to correct and restore these arrhythmias if they are detected. Evidence suggests that having an ICD can improve survival rates by 23%.²⁶ However, subsequent studies have been less convincing and there is a need for more research into which patient groups are most likely to benefit.²⁷

These interventions will not suit every patient, even if they ‘qualify’ and there are ethical issues which need to be addressed. However, for some people, they are literally a lifesaver. It is important, therefore, to consider whether someone with heart failure should be referred for consideration of CRT or an ICD once other therapeutic approaches have been optimised.

END OF LIFE CARE

The prognosis following a diagnosis of heart failure remains poor. People with heart failure will survive, on average, for around five years, which is a survival rate worse than many cancers.¹ As a result, end of life planning is an essential part of holistic heart failure care. Close collaboration between members of the multi-disciplinary team should ensure that the patient and their family get the best possible care, physically, emotionally, practically and spiritually, which allows them to plan for the end of life. Decisions need to be made about the place of dying, the level of intervention needed, and how to manage symptoms. As with most end of life conversations about death and dying, these should ideally not be left until the patient is dying but should be anticipated and planned for. Some people will need a lot of support to be able to have these discussions, others will be relieved that they are taking place. Discussions triggered by a request to put Lasting Powers of Attorney (LPA) documents in place may help relatives to understand what their loved one would want. For further information, see Advance care planning in this issue.

IN SUMMARY

Heart failure is the result of the inability of the heart to meet the circulatory needs of the body. HfrHF results from a failure of the left ventricle to pump out enough blood and the ejection fraction will normally be below 40-50%. HFpHF is associated with structural abnormalities of the heart, raised NT-pro-BNP levels and a normal ejection fraction. In many cases HFpEF is associated with the heart’s failure to fill adequately, a condition often linked to diastolic dysfunction. The majority of the evidence for pharmacological treatments is for HFrEF and there is very little evidence of successful drug therapies for HFpEF.

Key risk factors for heart failure include a history of myocardial infarction, hypertension or diabetes and may be triggered by conditions such as atrial fibrillation or thyroid disease. The signs and symptoms are often quite generic so careful assessment of anyone presenting with tiredness, breathlessness or oedema should be considered as a possible heart failure diagnosis, particularly if they have risk factors. If heart failure is suspected, an NT-pro-BNP blood test will help to risk stratify the individual so that echocardiography can be carried out appropriately. Other tests can help to identify co-morbid conditions and possible causes of heart failure. The management of heart failure is based around optimised doses of ACE inhibitors and beta blockers, with or without spironolactone or eplerenone. Newer medication options such as an ARNI (sacubitril/valsartan) can be considered. Recent trial data on SGLT2 inhibitors, specifically dapagliflozin, are highly likely to shine a spotlight on these drugs becoming part of the standard treatment for HFrEF in people with and without diabetes in the near future.

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