How can we improve the diagnosis of heart failure?

Abstract

Prevention and management of cardiovascular disease is a key priority for the National Health Service (NHS); it is central to the NHS England Long Term Plan, and from April 2022 it also forms a large proportion of the Direct Enhanced Service Contract for all primary care networks. Diagnosis and management of hypertension, hypercholesterolaemia and atrial fibrillation are routine in primary care but, despite increasing prevalence, heart failure is arguably falling behind. Heart failure can be challenging to diagnose and there may be few initial symptoms when patients first present. However, patient quality of life and life expectancy dramatically improve with an early diagnosis and prompt initiation of treatment. This article provides a framework for initial diagnosis and management in primary care.

Clinical case scenario

Anthony, a 45-year-old man, attends your morning clinic. On reviewing his past medical history he has hypertension and a family history of heart disease, with a late mother who had a myocardial infarction at the age of 52 years, and father with previous aortic valve repair when 66 years of age. You discover that he has worsening shortness of breath for the last few months, and a decline in his exercise tolerance, becoming more fatigued and only able to walk 500 m from his usual mile walk. He has been a smoker for a number of years, now five per day. He reports no ankle swelling throughout the course of the day, but notes episodes overnight when he wakes up in the early hours gasping for air and having to stand outside his front door. He has fine left basal crackles on auscultation and an elevated jugular venous pressure. He is concerned he cannot participate in his dance classes.

What would be your initial investigations?

What information would you give to Anthony?

Background

There are approximately a million people in the UK living with heart failure (HF), and despite an increasing portfolio of effective treatment options the burden of HF is increasing with population growth and ageing. In the UK this is comparable in incidence to the four most common cancers (Conrad et al., 2018).

Acute decompensated HF is the most common cause of emergency hospital admission in patients over 65 years in age (National Institute for Health and Care Excellence (NICE) 2021) and accounts for 2% of all NHS hospital bed occupancy. The management of HF accounts for ∼2% of the entire NHS budget, 70% of which is spent on acute hospital admissions (NICE, 2018). This increasing economic burden, combined with unfortunate disparities in diagnosis and access to specialist HF services, means we have to find new ways to support people living with HF.

The NICE impact report on cardiovascular disease management (February 2021), highlighted that 80% of patients are diagnosed as part of an acute emergency admission, despite 40% presenting with symptoms in primary care beforehand. The ‘Freedom from Failure’ campaign by the British Society for Heart Failure aims to raise public and clinician awareness of the symptoms of HF in order to aid early detection of the condition. Figure 1 summarises the current statistics for diagnosis and access to HF services.

Figure 1.

Current state of heart failure.

The ‘clinical syndrome’: Pathophysiology

The most recent European Society of Cardiology definition of HF is ‘a progressive clinical syndrome with signs and symptoms caused by a structural, or functional abnormality of the heart’: in essence, the heart becomes an inefficient pump (McDonagh et al., 2021).

There are two key HF phenotypes classified by measurement of the left ventricular ejection fraction (LVEF): HF where the ejection fraction is reduced to less than 40% (LVEF ≤ 40% (HFrEF)) and HF with a preserved ejection fraction of more than 40% (LVEF ≥ 40% (HFpEF)). In the early stages of HF, the body tries to compensate to maintain haemodynamic stability:

Reduced cardiac output and a low blood pressure activates the sympathetic and parasympathetic nervous systems to increase heart rate and force of ventricular contraction and thus, increase cardiac output

Reduced blood flow to the kidneys and subsequent decline in glomerular filtration rate activates the renin–angiotensin–aldosterone system (RAAS), which not only increases perfusion of the glomerulus, but also leads to sodium and water retention

Chronic activation of these mechanisms is detrimental and ultimately increases workload for the heart. This causes a vicious cycle of further fluid accumulation, which can lead to cardiac arrhythmias and adverse ventricular remodelling, however, with appropriate treatment, this downward spiral can be managed.

As the name suggests, HF was historically regarded as a palliative condition. Before the 1980 s treatment for HF was mainly bed rest and fluid restriction, with digoxin and diuretics as the only pharmacological options for patients. It was not until the 1990 s that treatment targeting neuro-hormonal mechanisms using combinations of drugs (angiotensin converting enzyme inhibitors, beta-blockers, and mineralocorticoid receptor antagonists) showed dramatic improvements in mortality and morbidity for HFrEF.

The clinical trajectory for a patient with HF is not predictable. Patients can have long periods of clinical stability interspersed with instability or ‘decompensations’ after which they may not return to their functional baseline. For many, HF becomes a terminal condition. The earlier the diagnosis, the better the support we can provide to patients, their families and their carers. With improved access to evidence-based treatment, patients can look forward to an improved quality of life, living with HF.

Epidemiology

In developed countries, the prevalence of known HF is estimated at 1 to 2% of the adult population (Roger, 2013). Both prevalence and incidence of HF increase with age, with 5% over the age of 75 years affected (British Heart Foundation, 2022).

The average age of a UK patient living with HF is 75 years, but there is regional variation. The average age of patients is lower if they are from Black or minority ethnic backgrounds and/or from the most socio-economically deprived groups.

Classification of heart failure

Approximately half of all patients with the HF syndrome have HFrEF, and this is the most comprehensively characterised phenotype. It is commonly caused by scar forming in the myocardium following a heart attack; the heart becomes weakened, cardiac output falls, and HF develops. Until very recently, all therapy for patients with HF applied only to those with HFrEF.

Patients with HFpEF (also known as HF with a normal ejection fraction or diastolic HF or dysfunction) are patients with symptoms and signs of HF but whose LVEF > 40%. The ventricle is often described as being stiff, causing reduced ventricular filling during diastole, although the actual pathophysiological mechanisms are more complex and poorly understood. The patient cohort is slightly different compared with HFrEF, typically older and female with a higher prevalence of co-morbidities such as atrial fibrillation and obesity.

There are currently no evidence-based treatment options available, although sodium glucose co-transporter-2 inhibitors (SGLT2) have shown promise in recent trials (Anker et al., 2021). Current guidelines recommend management of co-morbidities and symptomatic control with diuretics.

Assessment and examination

HF is a common cause of unplanned hospital admissions and these have risen by a third in the last 5 years. In-patient mortality is ∼10% and of those that survive to discharge one in four will be readmitted and one in eight will die in the following month (National Institute for Cardiovascular Outcomes Research, 2021). Hence, an early and accurate diagnosis is critical to allow patients to live a better quality of life for longer. Patients who are diagnosed following a hospital admission have significantly worse outcomes and a higher mortality than those who are diagnosed in primary care (Lawson et al., 2019).

If you suspect a patient may have HF, ask the patient about typical symptoms such as:

Fighting for breath (breathlessness): On exertion or at rest, when lying flat (orthopnoea), or waking gasping for air at night (paroxysmal nocturnal dyspnoea). Many patients may alter their routine or become more sedentary to avoid developing breathlessness

Fluid retention or swelling in areas of the body: This can affect the ankles, abdomen, and lead to overall weight gain

Fatigue, reduced exercise tolerance or inability to exercise

Less typical symptoms may include a nocturnal cough, wheezing, bloating, a reduced appetite, confusion, low mood, palpitations or dizziness/syncope. The New York Heart Association (NYHA) has a functional classification of HF based on severity of symptoms and limitation of activity (American Heart Association, 2017).

A number of risk factors can increase the likelihood of HF – take a detailed history and ask the patient about coronary artery disease, hypertension, atrial fibrillation, drug use (including alcohol) and a family history of HF or sudden cardiac death. Examine the patient and note any signs of HF, the most common of which are shown in Box 1. Box 1.

Signs of heart failure on clinical examination.

More specific signs:

• Elevated jugular venous pressure

• Third or fourth heart sounds

• Cardiomegaly with a displaced apex beat

• Hepato-jugular reflex

Less specific signs:

• Peripheral and dependent oedema

• Unintentional weight gain

• Weight loss of cachexia

• Cardiac murmur

• Crepitations

• Reduced air entry and dullness at bases

• Tachycardia >100 bpm

• Irregular pulse

• Tachypnoea

• Ascites

Physical examination, though recommended, can also have limitations as, particularly in the early stages, few may exhibit signs or symptoms. Some physical signs are difficult to interpret and can be related to other causes; others such as a raised jugular venous pressure (JVP) can be difficult to detect even if present. Table 1 shows the combined sensitivity and specificity values for common signs and symptoms of heart failure.

Table 1.

Sensitivity and specificity of symptoms and signs for presence of heart failure (ejection fraction <40%) in 1306 patients with coronary artery disease undergoing cardiac catheterisation.

	Sensitivity (%)	Specificity (%)
Symptom
Dyspnoea	66	52
Orthopnoea	21	81
Paroxysmal nocturnal dyspnoea	33	76
History of oedema	23	80
Sign
Raised JVP	10	97
Third heart sound	31	95
Peripheral oedema	10	93
Tachycardia	7	99
Crepitations	13	91

Source: Watson et al. (2000).

If HF is suspected, review the patient’s medicines and ask about supplements or over-the-counter preparations. Reduce or stop any that may cause or worsen heart failure, such as non-steroidal anti-inflammatories (including topical agents), thiazolidinediones (e.g. pioglitazone), doxazosin, rate-limiting calcium channel blockers (e.g. diltiazem) or dipeptidyl-peptidase 4 inhibitors (e.g. sitagliptin).

If there are signs of fluid accumulation, prescribe a loop diuretic and counsel the patient about this issue. Furosemide is first-line and a dose of 40 mg daily in the morning is a good starting dose for anyone who is treatment-naïve. Bumetanide may be more effective if a patient has gut oedema, as it has a better bioavailability compared with furosemide.

Measure N-terminal pro-B-type natriuretic peptide

Natriuretic peptides (NP) were first isolated from the porcine brain in 1988 - they are synthesised and released from the heart muscle in response to wall stretching due to pressure or volume overload (or both). NPs have an important protective physiological role for the heart and kidneys causing vasodilatation, natriuresis (and thus diuresis), inhibition of myocardial fibrosis, and inhibit the RAAS.

N terminal-pro-B-type NP (NT-pro-BNP) is the inactive fragment released from the precursor of BNP. It has a greater stability in blood sampling and is therefore preferred to BNP, but it is important to check what is available via your local pathology service, as the reference ranges are different. Although there are multiple causes of a raised NP concentration it has a high specificity and negative predictive value for HF - a normal result (<400 ng/L) excludes the diagnosis.

The NICE diagnostic pathway for heart failure is based on NP measurement, but up-take across the country is variable. NPs should also be included in local breathlessness pathways; they are essential to rule out other causes of dyspnoea.

If NT-pro-BNP concentrations are high, NICE recommends that patients are referred to a specialist to confirm diagnosis and the underlying cause:

If the NT-pro-BNP level is above 2000 pg/mL refer urgently for specialist assessment and echocardiography to be seen within 2 weeks – much like an urgent cancer referral

If the NT-pro-BNP level is between 400 and 2000 pg/mL refer for specialist assessment and echocardiography to be seen within 6 weeks

A level of NT-pro-BNP below 400 pg/mL means that HF failure is unlikely

The concentration of serum NP does not differentiate between types of HF – although those with HFpEF tend to have lower NP than those with HFrEF. It is also important to note that NP concentrations can be raised in other cardiac and non-cardiac conditions, such as acute coronary syndrome, valvular heart disease, atrial fibrillation, anaemia, advanced age (>70 years), renal failure, sepsis, liver failure, pulmonary hypertension or lung disease. NP levels may be reduced if the patient is already taking drugs affecting the RAAS or diuretics and this should be taken into account when interpreting the results.

NP testing is increasing in the UK, but a recent study in primary care showed only 39% of patients with symptoms have NT-pro-BNP levels measured or are referred for specialist review with echocardiogram (Hayhoe et al., 2019). Often NP testing is not considered, due to the common HF symptoms, such as breathlessness and fatigue, being associated with old age, de-conditioning (particularly during the impact of COVID-19) and presence of other respiratory disorders such as asthma or chronic obstructive pulmonary disease (COPD). High NP levels at diagnosis (>2000 pg/mL) are associated with a two-fold increase in HF-hospitalisation in the first year and a higher mortality (Taylor et al., 2022). Much like a 2-week wait referral for suspected malignancy, it is imperative that the diagnostic pathway for HF is also followed through.

Other investigations

Other initial investigations should include a 12-lead electrocardiogram (ECG) to determine heart rhythm, rate and QRS duration as a normal ECG makes heart failure unlikely. Measurement of other blood tests such as renal function, full blood count, iron studies (ferritin/TIBC/TSAT), thyroid function, liver function, and HbA1c can not only evaluate suitability for treatment, but also help to identify any reversible cause or relevant co-morbidity. These should be treated on their own merits. For example, the detection of iron deficiency anaemia should warrant investigations for gastrointestinal blood loss or malignancy.

Waiting for a specialist assessment can be a difficult time for patients and their GPs and healthcare providers. There are excellent support networks and resources available to signpost patients to such as the British Heart Foundation and patient-led charities such as Cardiomyopathy UK and Pumping Marvellous.

Clinical case scenario (continued)

You discuss potential diagnoses with Anthony and arrange blood tests and an ECG at the practice. His blood tests show an elevated NT-pro-BNP of 2200 pg/mL. His other blood tests are unremarkable and on discussion with the patient you prescribe furosemide 40 mg daily to help reduce his symptoms. His ECG shows LVH and he is referred to the urgent ‘one-stop’ HF clinic where an echocardiogram and assessment will be performed at the same clinic appointment. You arrange to telephone Anthony in a week’s time to review his symptoms, see how he is getting on with the water tablets, and to ensure he has received his cardiology appointment letter.

Emergency admission

If, at initial presentation a patient is acutely unwell with signs of haemodynamic instability, severe congestion (anasarca), breathlessness at rest (NYHA class IV), or acute pulmonary oedema, transfer to hospital should not be delayed.

Imaging and aetiology

Imaging is vital to confirm a diagnosis and distinguish between the phenotypes. Once referred for specialist review, a transthoracic echocardiogram is used to evaluate cardiac structure and function, and to measure the ejection fraction of the left ventricle. Beyond this, cardiologists may also refer patients for cardiac magnetic resonance imaging which allows more accurate estimation of the LVEF and clues to probable aetiology, such as identifying ischaemia where there may be scarred or fibrosed tissue. Once a patient has a confirmed diagnosis, a cardiologist will look to find an underlying cause for the HF. Box 2 includes the most common causes. Box 2.

Common causes of heart failure.

• Ischaemic heart disease

• Hypertension

• Valvular heart disease

• Cardiac muscle disease, e.g. dilated cardiomyopathy, hypertrophic cardiomyopathy, myocarditis, restrictive cardiomyopathy (amyloidosis)

• Congenital heart disease

• Arrhythmia

• Toxicity – drugs, alcohol

• Chronic kidney disease, e.g. end-stage renal failure

Regardless of where a person is diagnosed, NICE guidance then recommends that HF should be managed by a specialist multidisciplinary team (MDT) to optimise medications, provide the necessary information and support to the patient and their families, and to refer the patient to other services such as cardiac rehabilitation and palliative care.

Role of a GP and ongoing management in primary care

General practice is the ‘portal’ for detection of HF and the first step to earlier diagnosis which is linked to improved outcomes for those with the condition. The signs and symptoms of HF are common and non-specific and a low threshold for further investigation is needed to identify patients with possible disease. Although diagnosis requires specialist imaging and input, treatment of debilitating breathlessness and oedema due to venous congestion need not wait for a specialist to initiate it: diuretic treatment can be ongoing whilst diagnostic tests are awaited.

Only approximately one-in-three patients with a very high NT-pro-BNP concentration see a specialist within the recommended 2-week period. Ongoing treatment in the community during this phase is essential to reduce the risk of hospitalisation or death; in most cases, a large burden of this care will fall to primary care clinicians.

Once a diagnosis has been established and treatment initiated, follow up should be shared between primary and secondary care. Heart failure specialist nurses and rapid-access HF clinics are an essential source of support for patients with HF in the community. However, their availability is highly variable nationally and, again, a large part of ongoing care for patients with HF, including identifying and treating decompensations, is shouldered by those in primary care. With waiting times for out-patient cardiology services at an all-time high in the aftermath of the COVID-19 pandemic the situation is unlikely to improve in the short-to-medium term. However, there is growing recognition of the problems faced by primary care regarding the diagnosis and treatment of patients with HF in the community and there are multiple anecdotal accounts of successful integrated services across the country (British Heart Foundation, 2017).

At the time of their diagnosis an estimated 98% of HF patients in the UK have at least one other long-term condition, the most common being diabetes, ischaemic heart disease, hypertension, atrial fibrillation, or COPD. The longer term role of primary care is essential if a patient’s co-morbidities are to be coordinated, so as to ensure a patient-centred and holistic approach. Although the NICE quality standards for HF recommend that adults with stable chronic HF have a review of their condition at least every 6 months, this may be unrealistic for most primary care practices. Ongoing specialist input beyond diagnosis and at points in the patient’s HF pathway is important. It is worthwhile knowing what HF services are provided in your local area as access to HF specialist teams can help integrate care between primary and secondary care.

Key points

The incidence and prevalence of HF is increasing in the UK

General practice has a key role to investigate and refer patients suspected of having HF

The earlier patients are diagnosed, the better their survival and quality of life

One simple blood test can help signpost patients to the correct treatment pathway – use of NT-pro-BNP

Ongoing management of HF following a diagnosis, should be led by a specialist MDT

Footnotes

ORCID iD

Mrs Clare Thomson

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