Solutions focused research

Diagnosis and definition of heart failure

Heart failure is a cardio-renal syndrome that is the final common pathway for many cardiovascular diseases. It is usually diagnosed late when it is severe enough to require hospitalisation. The prognosis without optimal therapy and stabilisation is dire. Earlier recognition and management could be transformational.

Photo of 2 people making heart shape with hands

Main contact

Prof John GF Cleland (Robertson Centre for Biostatistics)

School of Health and Wellbeing research theme 

Solutions Focused Research

Related University of Glasgow beacon

Precision Medicine and Chronic Diseases

The challenge 

Heart failure is a common diagnosis, with an incidence similar to type-2 diabetes but with a much poorer prognosis and hence a lower prevalence. Up to 80% of cases in the UK are diagnosed only after an admission to hospital, although primary care physicians often recorded symptoms and signs that might be attributed to heart failure long before the hospital diagnosis. Within one year, 20–30% of those that survive this first admission will die. Administration of the four "foundational" therapies for heart failure with a reduced left ventricular ejection fraction can improve prognosis substantially but only after a diagnosis has been made. Earlier diagnosis enables earlier intervention. 

The research 

Better methods of diagnosing heart failure are required. Current guidelines rely on symptoms and signs, which are late and subjective manifestations of disease. Two strategies may be considered:

  1. Screening tests for people at risk of developing clinically symptomatic heart failure (e.g. chronic hypertension or diabetes, ischaemic heart disease, chronic kidney disease)
    • A blood test (NT-proBNP) can be used to identify people with cardio-renal problems leading to congestion (which usually precedes the development of symptoms and signs by months or years)
    • An echocardiogram can be used to identify congestion. Hand-held devices supported by artificial intelligence are making this technology much more accessible in primary care
    • A stepwise approach of blood test followed by confirmatory echo may be the most practical and accurate strategy
  2. Identification of patients receiving treatment for symptoms and/or signs suggestive of heart failure but who have not yet been diagnosed with heart failure

The results

The HOMAGE clinical trial (reference 4) found that many patients with or at high risk of ischaemic heart disease have increased plasma concentrations of NT-proBNP, which is associated with left atrial dilation (a sign of congestion). Although these patients were not considered to have heart failure, they had reduced exercise capacity and, when asked, they reported breathlessness on only moderate exertion; in other words they did fulfil all the criteria for heart failure.

Participants were then randomised to spironolactone or a control group, which reduced blood pressure substantially and also plasma NT-proBNP and left atrial volume and had favourable effects on blood markers of myocardial fibrosis.

Analysis of several large sets of electronic health records from the UK indicates that many more patients are initiated on furosemide or bumetanide (loop diuretics) than are diagnosed with heart failure. There are very few good indications for these agents other than the treatment of symptoms and signs that are typical for heart failure. Analysis shows that patients treated with loop diuretics have a similar prognosis to patients with heart failure. Indeed, prognosis is more strongly related to the use of loop diuretics than to the diagnosis of heart failure (having both is worst).

Re-analysis of international trials confirms that patients treated with loop diuretics have an adverse prognosis whether or not they have a concomitant diagnosis of heart failure.

Further analyses have shown a strong link between iron deficiency, anaemia and the risk of developing and prognosis of heart failure.

The impact 

We should no longer base a diagnosis of heart failure on symptoms and signs but rather on objective markers such as NT-proBNP and left atrial volume.

NT-proBNP is the strongest predictor of survival in studies of many different cardiovascular, renal or metabolic diseases. Echocardiographic markers of congestion (such as left atrial volume) are the strongest prognostic imaging markers.

Health services should audit the use of loop diuretics and ensure that appropriate investigations are done for all patients receiving these agents.

The HOMAGE trial suggests that spironolactone might be an effective intervention for delaying or preventing progression of cardiac dysfunction to clinically overt heart failure.

The team

Related publications 

  1. Only people with increased plasma concentrations of natriuretic peptides should be included in outcome trials of diabetes, cardiovascular and kidney disease: implications for clinical practice. Cleland JGF, Butler J, Januzzi JL Jr, Pellicori P, McDonagh T. Eur J Heart Fail. 2022 Mar 17
  2. To master heart failure, first master congestion. Cleland JGF, Pellicori P. Lancet. 2021 Sep 11;398(10304):935-936.
  3. The struggle towards a Universal Definition of Heart Failure – how to proceed? Cleland JGF, Pfeffer MA, Clark AL, Januzzi JL, McMurray JJV, Mueller C, Pellicori P, Richards M, Teerlink JR, Zannad F, Bauersachs J. Eur Heart J. 2021 Jun 21;42(24):2331-2343
  4. The effect of spironolactone on cardiovascular function and markers of fibrosis in people at increased risk of developing heart failure: the heart 'OMics' in AGEing (HOMAGE) randomized clinical trial. Cleland JGF, Ferreira JP, Mariottoni B, Pellicori P, Cuthbert J, Verdonschot JAJ, Petutschnigg J, Ahmed FZ, Cosmi F, Brunner La Rocca HP, Mamas MA, Clark AL, Edelmann F, Pieske B, Khan J, McDonald K, Rouet P, Staessen JA, Mujaj B, González A, Diez J, Hazebroek M, Heymans S, Latini R, Grojean S, Pizard A, Girerd N, Rossignol P, Collier TJ, Zannad F; HOMAGE Trial Committees and Investigators. Eur Heart J. 2021 Feb 11;42(6):684-696.
  5. Use of diuretics and outcomes in patients with type 2 diabetes: findings from the EMPA-REG OUTCOME trial. Pellicori P, Fitchett D, Kosiborod MN, Ofstad AP, Seman L, Zinman B, Zwiener I, Wanner C, George J, Inzucchi SE, Testani JM, Cleland JGF. Eur J Heart Fail. 2021 Jul;23(7):1085-1093. 
  6. Ultrasound imaging of congestion in heart failure: examinations beyond the heart. Pellicori P, Platz E, Dauw J, Ter Maaten JM, Martens P, Pivetta E, Cleland JGF, McMurray JJV, Mullens W, Solomon SD, Zannad F, Gargani L, Girerd N. Eur J Heart Fail. 2021 May;23(5):703-712
  7. Prevalence, pattern and clinical relevance of ultrasound indices of congestion in outpatients with heart failure. Pellicori P, Shah P, Cuthbert J, Urbinati A, Zhang J, Kallvikbacka-Bennett A, Clark AL, Cleland JGF. Eur J Heart Fail. 2019 Jul;21(7):904-916
  8. Cardiac Dysfunction, Congestion and Loop Diuretics: their Relationship to Prognosis in Heart Failure. Pellicori P, Cleland JG, Zhang J, Kallvikbacka-Bennett A, Urbinati A, Shah P, Kazmi S, Clark AL. CV Drugs Ther. 2016;30:599-609.
  9. Prevalence of markers of heart failure in patients with atrial fibrillation and the effects of ximelagatran compared to warfarin on the incidence of morbid and fatal events: a report from the SPORTIF III and V trials. Cleland JG, Shelton R, Nikitin N, Ford S, Frison L, Grind M. Eur J Heart Fail. 2007 Jun-Jul;9(6-7):730-9. 
  10. Criteria for Iron Deficiency in Patients With Heart Failure. Masini G, Graham FJ, Pellicori P, Cleland JGF, Cuthbert JJ, Kazmi S, Inciardi RM, Clark AL. J Am Coll Cardiol. 2022 Feb 1;79(4):341-351. 
  11. Natural history and prognostic significance of iron deficiency and anaemia in ambulatory patients with chronic heart failure. Graham FJ, Masini G, Pellicori P, Cleland JGF, Greenlaw N, Friday J, Kazmi S, Clark AL. Eur J HF. 2021 May 28. 

Related URLs

This research is supported by Heart Research UK and British Heart Foundation.

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