Intended for healthcare professionals

Practice Rational Testing

Investigating suspected heart failure

BMJ 2013; 346 doi: (Published 24 April 2013) Cite this as: BMJ 2013;346:f2442
  1. Tushar Kotecha, cardiology specialist registrar,
  2. Kevin Fox, consultant cardiologist
  1. 1Charing Cross Hospital, Imperial Healthcare NHS Trust, London W6 8RF, UK
  1. Correspondence to: K Fox{at}

The authors explore the most appropriate initial investigations and referrals for use by doctors in primary care

Learning points

  • Patients with symptoms suggestive of heart failure who have had a myocardial infarction or have a raised B-type natriuretic peptide concentration should be referred to a cardiologist for further assessment

  • A normal 12 lead electrocardiogram and B-type natriuretic peptide <35 pg/mL (or N-terminal pro-B-type natriuretic peptide <125 pg/mL) have high negative predictive values for excluded heart failure in a non-acute setting

  • B-type natriuretic peptide >400 pg/mL or N-terminal pro-B-type natriuretic peptide >2000 pg/mL confers a poor prognosis, and such patients should be reviewed by a cardiologist within two weeks

  • Echocardiography remains the imaging modality of choice in confirming a diagnosis of heart failure

A 70 year old man presents to his general practitioner with a four week history of breathlessness on exertion. He currently takes bendroflumethiazide 2.5 mg daily for hypertension and uses inhalers for chronic obstructive pulmonary disease. He has no history of cardiac disease. His brother had a myocardial infarction in his 70s. The patient used to smoke 20 cigarettes a day but gave up smoking two years ago; he denied alcohol excess. On examination, his blood pressure was 150/95 mm Hg with a pulse of 90 beats/min. Heart sounds were normal and, on chest auscultation, he had bibasal inspiratory crepitations and scattered wheeze. His jugular venous pressure was not visible and he had mild bilateral ankle oedema.

What are the next investigations?

Breathlessness is a common presentation in general practice and emergency departments. The clinical diagnosis of heart failure can be challenging as signs and symptoms may be non-specific.1 In the United Kingdom the 2010 guidelines from the National Institute for Health and Clinical Excellence (NICE) recommend that when heart failure is suspected, the initial investigations listed below are useful in primary care.2

12 lead electrocardiography

An electrocardiogram can be obtained immediately and provides useful information about heart rhythm and electrical conduction. It may also show evidence of left ventricular hypertrophy or previous infarct (with the presence of Q waves).1 A normal electrocardiogram has a 90% negative predictive value for excluding systolic heart failure.3

Chest radiography

In our case, the patient’s history and clinical findings required a chest radiograph within days to look for features suggestive of heart failure (such as pulmonary oedema, pleural effusions, and upper lobe diversion) and to exclude other causes of breathlessness, such as infection or malignancy.

Serum natriuretic peptide measurement

Serum concentrations of both B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide are raised in heart failure and correlate with severity.4 Increased myocardial wall stress from volume loading or pressure loading in heart failure activates the B-type natriuretic peptide gene in cardiomyocytes,5 releasing the biologically active B-type natriuretic peptide and the inert aminoterminal fragment N-terminal pro-B-type natriuretic peptide. B-type natriuretic peptide stimulates natriuresis and vasorelaxation, and inhibits renin, aldosterone, and sympathetic nervous activity. In healthy individuals, circulating concentrations of both the natriuretic peptides are usually very low. B-type natriuretic peptide >100 pg/mL and N-terminal pro-B-type natriuretic peptide >900 pg/mL each have a 90% sensitivity for the diagnosis of heart failure.4 6 Both are prognostic predictors of mortality and adverse cardiovascular events, and the higher the concentration the worse the prognosis (in a linear fashion).7 Additionally, trial data suggest that a fall of more than 30% in natriuretic peptide concentration on treatment confers a better prognosis than a failure to fall,8 although current UK guidelines do not recommend serial measurements.2

Natriuretic peptide measurement is a useful screening tool to exclude heart failure and reduce referrals for echocardiography when availability is limited or may be delayed.9 At a cut-off value of 35 pg/mL, B-type natriuretic peptide provides a negative predictive value of 93%.10 For N-terminal pro-B-type natriuretic peptide, a value <125 pg/mL provides a negative predictive value of 97%.10

Natriuretic peptide concentrations may be modestly raised in the absence of heart failure (box). Of note, obesity results in lower than expected concentrations.4

Causes of modestly raised concentrations of natriuretic peptides in the absence of heart failure4

  • Left ventricular hypertrophy

  • Cardiac ischaemia

  • Tachyarrhythmias

  • Hypoxaemia

  • Chronic obstructive pulmonary disease

  • Diabetes mellitus

  • Renal impairment

  • Liver cirrhosis

  • Sepsis

The NICE guidance advises that patients with B-type natriuretic peptide >400 pg/mL or N-terminal pro-B-type natriuretic peptide >2000 pg/mL should be seen by a cardiologist within two weeks as concentrations in this range carry a poorer prognosis.2 Those with suspected heart failure and previous myocardial infarction should be referred for echocardiography regardless of natriuretic peptide concentration.2

Given the high negative predictive value of electrocardiography and natriuretic peptides, a normal electrocardiogram and B-type natriuretic peptide <35 pg/mL (or N-terminal pro-B-type natriuretic peptide <125 pg/mL) make a diagnosis of heart failure highly unlikely in the non-acute setting.1 9

Further blood tests

Further blood tests, which can be requested before referral, should include the tests listed below.1 2

  • Full blood count—Anaemia may precipitate heart failure or provide an alternative explanation for breathlessness. Neutrophilia may suggest an infective component to breathlessness.

  • Renal function—Renal failure may cause fluid overload. About 87% of patients with heart failure have a creatinine clearance of <90 mL/min and this carries a worse prognosis.11 Baseline renal function is essential as treating heart failure with angiotensin converting enzyme (ACE) inhibitors and diuretics may worsen renal function and cause electrolyte imbalance.

  • Liver function—Impaired liver function with an obstructive picture may indicate hepatic congestion resulting from right heart failure. Hypoalbuminaemia may cause fluid retention leading to peripheral oedema.

  • Lipid profile—Hyperlipidaemia increases cardiovascular risk and requires appropriate treatment.

  • Glucose or haemoglobin A1cUse this to establish the presence of diabetes, which often occurs alongside cardiac disease.

  • Thyroid function—Subclinical hypothyroidism and hyperthyroidism confer a higher risk of developing heart failure and require appropriate treatment.12

When a diagnosis of heart failure is uncertain

When a diagnosis of heart failure is uncertain, other investigations—such as spirometry and lung function tests—may be requested. Additionally, 9-41% of patients with heart failure have coexisting lung disease such as chronic obstructive pulmonary disease13 and require optimal treatment of both.

As the NICE guidance recommends, refer patients with suspected heart failure to specialist cardiology services, which can establish the diagnosis, investigate aetiology, and start treatment.2 Further investigation by a cardiologist may include echocardiography, coronary angiography, and cardiac magnetic resonance imaging.


Echocardiography continues to be the imaging modality of choice in confirming the diagnosis of heart failure.1 2 It can be used to assess chamber volumes and wall thickness, left ventricular systolic and diastolic function, right ventricular function, and valvular disease.1

Coronary angiography

Consider coronary angiography to assess for the presence of coronary artery disease, which has been shown to be the cause of heart failure in about half of patients under 75 years,1 14 However, do this only after treating any acute decompensation of heart failure and only if coronary intervention were to be considered to be appropriate. Percutaneous or surgical intervention may be indicated if there is evidence of angina or inducible ischaemia on functional testing (such as stress echocardiography or myocardial perfusion scan).15 16

Cardiac magnetic resonance imaging

Cardiac magnetic resonance imaging may be useful in patients for whom echocardiographic images are suboptimal or the aetiology of heart failure remains unclear.1 It is particularly useful when inflammatory and infiltrative conditions are suspected. Cardiac magnetic resonance imaging provides the most accurate and reproducible measures of volume, mass, and wall motion, but its use is currently limited by cost and availability.1


Our patient’s electrocardiogram showed left bundle branch block and his serum B-type natriuretic peptide was raised, at 1100 pg/mL, prompting immediate referral to a cardiologist for further assessment. Chest radiography showed hyperexpanded lung fields consistent with chronic obstructive pulmonary disease, and upper lobe diversion with mild pulmonary oedema. Echocardiography showed moderate left ventricular systolic impairment with normal valves, confirming heart failure. Treatment was started immediately with a loop diuretic, aldosterone antagonist, and ACE inhibitor. Bendroflumethiazide was stopped. Coronary angiography showed diffuse atheromatous disease, suggesting coronary artery disease as the cause of his heart failure. Over a few weeks, his ACE inhibitor dose was up-titrated and a β blocker introduced, resulting in improvement in his breathlessness.


Cite this as: BMJ 2013;346:f2442


  • This series of occasional articles provides an update on the best use of key diagnostic tests in the initial investigation of common or important clinical presentations. The series advisers are Steve Atkin, professor, head of department of academic endocrinology, diabetes, and metabolism, Hull York Medical School; and Eric Kilpatrick, honorary professor, department of clinical biochemistry, Hull Royal Infirmary, Hull York Medical School. To suggest a topic for this series, please email us at practice{at}

  • Contributors: Both authors contributed to conception and design. TK drafted the article and KF critically revised it. Both authors approved the final version. KF is the guarantor.

  • Competing interests: Both authors have completed the ICMJE uniform disclosure form at (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Provenance and peer review: Commissioned; externally peer reviewed.

  • Patient consent not required (patient anonymised, dead, or hypothetical).


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