Heart failure is a common complex clinical syndrome of symptoms and signs caused by impairment of the heart’s action as a pump supporting the circulation.
Heart Failure with Preserved Ejection Fraction (HF-PEF), previously known as “diastolic” heart failure, is characterised by normal left ventricular systolic function despite symptoms and signs of heart failure.
There is no single diagnostic test. Use clinical judgement based on history, physical examination and investigations.
Diagnosis may be confirmed by a combination of:
HF-PEF accounts for roughly half of all cases of heart failure. It is more common in older patients, women and those with multiple co-morbidities.
The diagnosis is easy to miss. Chronic symptoms such as fatigue and reduced exercise tolerance may not be readily attributed to heart failure, especially in the context of multi-morbidities and/or a normal echocardiogram.
Definition of preserved left ventricular ejection fraction (LVEF)
There is not worldwide consensus on this, but a LVEF >40% is generally thought to represent preserved ejection fraction.
Heart failure (of all types) may be classified by symptoms
New York Heart Association (NYHA) Functional Classification3:
| Class | Description | |
| I | No limitation of physical activity | Ordinary physical activity does not cause undue fatigue, palpitation, shortness of breath |
| II | Slight limitation of physical activity | Ordinary physical activity results in fatigue, palpitation, shortness of breath |
| III | Marked limitation of physical activity | Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, or shortness of breath |
| IV | Unable to carry on any physical activity without discomfort | Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases |
References
1)National Institute for Health and Care Excellence. Chronic Heart Failure in Adults: diagnosis and management [Internet]. [London]: NICE; 2018 (NICE guideline [NG181])
2)Ponikowski P, Voors AA, Anker SD et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 2016; 37(27): 2129–2200
3)Dolgin M, Association NYH, Fox AC, Gorlin R, Levin RI, New York Heart Association. Criteria Committee. Nomenclature and criteria for diagnosis of diseases of the heart and great vessels. 9th ed. Boston, MA: Lippincott Williams and Wilkins; March 1, 1994
Untreated, heart failure is progressive and carries a poor prognosis:
These selected figures are a guide, though there is significant uncertainty:
Overall survival rates
| Survival rates at: | 1 year | 5 years | 10 years | 15 years |
| 81% | 48% | 26% | 13% | |
|
Year of initial diagnosis* |
2016 | 2012 | 2007 | 2000 |
* Defined by first recorded clinical code
Source: UK Primary Care database study 20192
Survival rates by age at diagnosis
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| Survival rates at: | 1 year | 5 years | 10 years | 15 years |
| Age: 45-54 years | 90% | 79% | 65% | 54% |
| 55-64 | 88% | 71% | 52% | 38%% |
| 65-74 | 84% | 59% | 35% | 17% |
| 75-84 | 77% | 43% | 18% | 6% |
| 85-94 | 63% | 22% | 4% | 0.2% |
| ≥95 | 44% | 6% | – | – |
Source: UK Primary Care database study 20192
Survival rates for HF-REF v HF-PEF v LVSD without HF
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| Survival rate at: | 5 years | 10 years |
| HF-REF | 53% | 27% |
| HF-PEF | 62% | 26% |
| LVSD* ≤40% but no HF | 69% | 38% |
* LVSD, left ventricular systolic dysfunction
Source: UK Primary Care cohort study 20143
Similar differences are seen in studies around the world over time:
| Survival rate at: | 5 years |
| HF-REF | 63% |
| HF-PEF | 70% |
Source: Systematic review 20191 (pools data from studies 1987-2017)
Survival rates by NT-proBNP level
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| Survival rate at: | 1 year | 5 years | 10 years |
| NT-proBNP*: <400 | 79% | 54% | 30% |
| 400-1999 | 81% | 50% | 24% |
| ≥2000 | 73% | 38% | 18% |
* NT-proBNP measured at time of diagnosis, pg/ml.
Source: UK Primary Care database study 20204
Survival rates by diagnosis at hospital admission v community
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Survival rates are worse for those first diagnosed during acute hospital admission:
| Survival rate at: | 1 year | 5 years | 10 years | 15 years |
| Diagnosed in community | 81% | 52% | 29% | 15% |
| Diagnosed at hospital admission | 69% | 37% | 18% | 8% |
Source: UK Primary Care database study 20192
Survival rates men v women
more
References
more
1)Jones NR, Roalfe AK, Adoki I et al. Survival of patients with chronic heart failure in the community: a systematic review and meta-analysis. Eur J Heart Fail 2019; 21: 1306-1325
2) Trends in survival after a diagnosis of heart failure in the United Kingdom 2000-2017: population based cohort study.
3)Taylor CJ, Roalfe AK, Iles R, Hobbs FR. Ten-year prognosis of heart failure in the community: follow-up data from the Echocardiographic Heart of England Screening (ECHOES) study. Eur J Heart Fail 2012; 14: 176-184
4) et al. Natriuretic peptide level at heart failure diagnosis and risk of hospitalisation and death in England 2004–2018
5), Jones NR et al. National trends in heart failure mortality in men and women, United Kingdom, 2000–2017. Eur J Heart Fail 2021; 23: 3-12
Diuretics
Loop diuretics reduce symptoms and signs of fluid overload.
Many patients may need to remain on a maintenance dose, though these do not need to be continued once fluid overload has resolved and if it does not recur.
Managing co-morbidities
Optimising the management of general cardiovascular risk factors is advised, as this improves prognosis overall, though there is no evidence of a direct effect on the progression of HF-PEF itself.
Optimising management of other co-morbidities such respiratory disease or angina may improve general symptoms such as breathlessness and exercise tolerance.
Long-term therapies
Unfortunately, there is no evidence that the usual range of treatments available for HF-REF (such as ACE inhibitors, beta-blockers or MRAs) improve prognosis for those with HF-PEF.
SGLT2 inhibitors
However, there is evidence of benefit of SGLT2 inhibitors in HF-PEF – see the section below
NICE recommends empagliflozin or dapagliflozin as options for treating symptomatic chronic heart failure with preserved or mildly reduced ejection fraction:
The data below describes evidence about empagliflozin, but dapagliflozin has an equal effect.
Figures derived from a single RCT on empagliflozin (EMPEROR-Preserved)1 which informed a 2023 NICE technology appraisal2 (this treatment did not feature in the 2018 guideline).
A second RCT on dapagliflozin (DELIVER)3 informed another 2023 NICE technology appraisal4.
References
1)National Institute for Health and Care Excellence.Empagliflozin for treating chronic heart failure with preserved or mildly reduced ejection fraction. 2023 [Internet]. [London]: NICE; 2023. (Technology appraisal guidance [TA929])
2)EMPEROR-Preserved Trial Investigators. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. N Engl J Med 2021; 385:1451-1461
3(National Institute for Health and Care Excellence. Dapagliflozin for treating chronic heart failure with preserved or mildly reduced ejection fraction. 2023 [Internet]. [London]: NICE; 2023. (Technology appraisal guidance [TA902])
4)DELIVER Trial Committees and Investigators.Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction. N Engl J Med 2022; 387:1089-1098
| This research provides a very good indication of the treatment effect.
However, it is possible that the true effect is slightly smaller or greater. |
NICE appraised this RCT as having
References
1)National Institute for Health and Care Excellence.Empagliflozin for treating chronic heart failure with preserved or mildly reduced ejection fraction. 2023 [Internet]. [London]: NICE; 2023. (Technology appraisal guidance [TA929])
2)EMPEROR-Preserved Trial Investigators. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. N Engl J Med 2021; 385:1451-1461
The population characteristics in this trial1 were:
Reference
1)EMPEROR-Preserved Trial Investigators. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. N Engl J Med 2021; 385:1451-1461
The EMPEROR-Preserved trial1 (which provides the data on benefits here), showed no increase in the following adverse events with empagliflozin treatment:
Other harms were reported in this trial:
| Placebo | Empagliflozin | Absolute Risk Increase | Number Needed to Harm | |
| Symptomatic hypotension | 5.2% | 6.6% | 1.4% | 71 |
| Urinary tract infections | 8.1% | 9.1% | 1% | 100 |
| Discontinuation of treatment due to side effects | 18.4% | 19.1% | 0.7% | 142 |
note: these are absolute figures and were not reported with any calculation of statistical significance
However, this was one trial in a particular population:
Reference
1) EMPEROR-Preserved Trial Investigators. Empagliflozin in Heart Failure with a Preserved Ejection Fraction. N Engl J Med 2021; 385:1451-1461
People who have an adverse event
People whose adverse event is prevented by treatment
People who were never going to have an adverse event anyway
Graphics and NNTs are rounded to the nearest integer
These three statistical terms offer three different ways of looking at the results of trial data.
Absolute Risk Reduction
This tells you how many people out of 100 who take a treatment have an adverse event prevented.
MoreThe value of the ARR changes with the baseline risk of the person (or population) taking the treatment. The higher the starting risk, the greater the absolute chance of benefit.
You need to think about over what time the trial data show this benefit, as it is usually assumed that more absolute risk reduction is gained over time.
Your patient might be taking the treatment for much longer than the length of a clinical trial (or, if life expectancy is limited, perhaps for less time).
Number Needed to Treat
This tells you how many people need to take the treatment in order for one person to avoid an adverse event.
The lower the number, the more effective the treatment.
MoreThe value of the NNT changes with the baseline risk of the person (or population) taking the treatment. The higher the starting risk, the smaller the NNT.
You need to think about over what time the trial data show benefit, as it is usually assumed that more benefit is gained over time and therefore the NNT will drop over time.
Your patient might be taking the treatment for much longer than the length of a clinical trial (or, if life expectancy is limited, perhaps for less time).
Relative Risk Reduction
This tells you the proportion of adverse events that are avoided if the entire population at risk is treated.
MoreThe value of the RRR is usually constant in people (or populations) at varying degrees of risk.
It is also usually assumed to stay constant over time.
This can be helpful, especially when thinking about population outcomes, but can be misleading for an individual person:
For example, a RRR of 25% in someone with a baseline risk of 40% would give them an ARR of 10% and an NNT of 10.
A RRR of 25% in someone with a baseline risk of 4% would give them an ARR or 1% and an NNT of 100.
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