Heart Failure With a Normal Pump?

Heart failure with preserved ejection fraction — known as HFpEF  is one of Australia’s most common, and least understood, forms of heart disease. A diagnosis can be confusing: people are told their heart is failing, yet the heart appears to pump normally. Understanding what’s actually happening, what contributes to it, and what treatment options exist has never been more important — particularly as new research is rapidly changing the outlook for those living with this condition.

At Life Clinical Research (LCR) in Ipswich, Queensland, we currently have an open clinical trial for people with HFpEF. This article aims to explain the condition clearly for patients, families, and carers alike.

 What is HFpEF? 

The heart has two key functions on every beat: it squeezes to push blood out, and it relaxes to fill back up. “Ejection fraction” measures the squeezing part. In HFpEF, the squeeze is normal — it’s the relaxation that’s impaired.

When the heart muscle becomes stiff, it can’t fill properly between beats. Pressure builds, fluid accumulates, and the result is the breathlessness, fatigue, and swelling that typically bring people to their doctor.

Around half of all Australians living with heart failure have HFpEF, and that proportion is rising — driven by an ageing population and increasing rates of obesity and diabetes.^¹

 The Obesity Connection and Key Risk Factors

One of the most significant findings in recent HFpEF research is how strongly the condition is linked to excess body weight. Studies suggest that around 80% of people with HFpEF are overweight or obese.^¹ Obesity appears to drive HFpEF through several mechanisms: excess abdominal fat releases inflammatory signals that stiffen the heart muscle; a larger body demands more cardiac output, raising pressure and strain; and metabolic disruption from obesity elevates blood pressure, promotes fluid retention, and impairs the heart’s filling function.

Research has also identified a dose-response relationship — the greater the weight loss achieved, the greater the cardiac benefit. More on that below.

HFpEF typically develops in people with a combination of risk factors, including: high blood pressure (the most common contributor), type 2 diabetes, atrial fibrillation, coronary artery disease, chronic kidney disease, obstructive sleep apnoea, advanced age (risk rises significantly after 70), and female sex — women are disproportionately affected.

Symptoms

HFpEF typically develops in people with a combination of risk factors, including: high blood pressure (the most common contributor), type 2 diabetes, atrial fibrillation, coronary artery disease, chronic kidney disease, obstructive sleep apnoea, advanced age (risk rises significantly after 70), and female sex — women are disproportionately affected.

Diagnosis

Diagnosis involves blood tests including BNP or NT-proBNP (biomarkers that signal cardiac stress), an ECG, and an echocardiogram — a cardiac ultrasound that assesses how well the heart fills and whether structural abnormalities are present.

Because the ejection fraction appears normal, HFpEF can be missed on initial assessment. Specialist review by a cardiologist is often required for a confident diagnosis, particularly in borderline cases.

Diagnosis and Evidence for Weight Loss

For many years, HFpEF was considered difficult to treat. That has changed significantly.

Management is centred on addressing underlying contributors — blood pressure control, glycaemic management, treatment of sleep apnoea, and weight reduction where appropriate. Diuretics are commonly used to relieve congestion.

SGLT2 inhibitors, a drug class originally developed for type 2 diabetes — have become a cornerstone of HFpEF management. The EMPEROR-Preserved and DELIVER trials demonstrated that empagliflozin and dapagliflozin meaningfully reduce hospitalisations in HFpEF, including in patients without diabetes, and both are now recommended across international guidelines.^²³

What Research Shows on Weight Loss

The evidence linking weight loss to improved HFpEF outcomes is now substantial, drawn from multiple peer-reviewed studies:

Dietary intervention (SECRET trial, JAMA 2016): This randomised controlled trial found that caloric restriction in obese older patients with HFpEF significantly improved exercise capacity and quality of life — with benefits attributed to genuine physiological improvement, not simply reduced mechanical load.^⁴

Semaglutide (STEP-HFpEF, NEJM 2023): In 529 patients with obesity and HFpEF, semaglutide produced 10.7% greater weight loss than placebo, alongside significant improvements in symptoms and physical function, and a marked reduction in heart failure events — 1 hospitalisation or urgent visit in the semaglutide group versus 12 in placebo.^⁵ A prespecified Nature Medicine analysis confirmed the dose-response: greater weight loss produced greater cardiac benefit.^⁶ These findings were replicated in patients with concurrent type 2 diabetes in STEP-HFpEF DM (2024).^⁷

Tirzepatide (SUMMIT trial, NEJM 2025): In 731 patients across 9 countries, tirzepatide significantly reduced the combined risk of cardiovascular death and worsening heart failure events, and improved symptoms and exercise capacity.^⁸ A cardiac MRI substudy demonstrated a measurable reduction in left ventricular mass correlated with weight loss — structural evidence that the heart remodels favourably.^⁹

Bariatric surgery: A large population-based study found a greater than 40% reduction in heart failure hospitalisations in the two years following bariatric surgery in patients with obesity and heart failure.^¹⁰

Clinical Trials: Why they Matter

HFpEF remains an active area of research, and clinical trials are how better treatments are found and validated. Participating in a trial gives people access to emerging therapies under close medical supervision, while contributing directly to knowledge that benefits future patients.

Life Clinical Research in Ipswich, Queensland currently has an open clinical trial for people with HFpEF. Our team is happy to answer questions, outline what participation involves, and help determine whether a trial may be suitable with no obligation 

Frequently Asked Questions:

Is HFpEF the same as diastolic heart failure?

HFpEF was previously referred to as diastolic heart failure. The terminology has evolved because the condition is now understood to involve multiple systems — kidneys, lungs, vasculature, and inflammatory pathways — beyond diastolic dysfunction alone. HFpEF is the current preferred term among specialists.

Can HFpEF be reversed?

HFpEF is not currently considered fully reversible, but it is manageable. With appropriate treatment, many people maintain a good quality of life and experience significantly fewer hospitalisations. Clinical research is actively working to identify disease-modifying therapies.

Does weight loss help HFpEF?

For people with obesity-related HFpEF, the peer-reviewed evidence — including two large New England Journal of Medicine trials — clearly indicates that intentional weight loss improves symptoms, exercise capacity, and clinical outcomes, with greater benefit seen with greater weight loss. A treating doctor or specialist can advise on appropriate approaches for an individual’s circumstances.

REFERENCES:

1. Heart failure with preserved ejection fraction in patients with obesity. Heart, Lung and Circulation, 2025. ScienceDirect
2. Heidenreich PA, et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. Circulation. 2022;145(18):e895–e1032. Full text
3. Metra M, et al. SGLT2 inhibitors for the prevention and treatment of heart failure. ESC Heart Failure, 2025. Full text
4. Kitzman DW, et al. Caloric restriction or aerobic exercise training in obese older patients with HFpEF. JAMA. 2016;315(1):36–46. DOI: 10.1001/jama.2015.17346
5. Kosiborod MN, et al. Semaglutide in patients with HFpEF and obesity (STEP-HFpEF). N Engl J Med. 2023;389:1069–1084. DOI: 10.1056/NEJMoa2306963
6. Kosiborod MN, et al. Semaglutide in HFpEF by obesity class and weight reduction: prespecified analysis. Nature Medicine, 2023. PubMed
7. Kosiborod MN, et al. Semaglutide in obesity-related HFpEF and type 2 diabetes (STEP-HFpEF DM). N Engl J Med. 2024. DOI: 10.1056/NEJMoa2313917
8. Packer M, et al. Tirzepatide for HFpEF and obesity (SUMMIT). N Engl J Med. 2025;392(5):427–437. DOI: 10.1056/NEJMoa2410027
9. Borlaug BA, et al. Tirzepatide reduces LV mass and paracardiac adipose tissue in HFpEF: SUMMIT CMR substudy. J Am Coll Cardiol. 2024. JACC
10. Shimada YJ, et al. Bariatric surgery and heart failure hospitalisations. J Am Coll Cardiol. 2016;67:895–903. DOI: 10.1016/j.jacc.2015.12.016
11. Kittleson MM, et al. 2023 ACC Expert Consensus Decision Pathway on Management of HFpEF. J Am Coll Cardiol, 2023. Full text
12. BMJ Best Practice: Heart failure with preserved ejection fraction. Evidence last reviewed May 2026. BMJ Best Practice
13. Heart Foundation Australia — Heart Failure. heartfoundation.org.au
14. Therapeutic Goods Administration — Clinical Trials. tga.gov.au

👉 Learn more or participate in a study: https://lcr.health

Disclaimer

This article is for general educational and informational purposes only. It does not constitute medical advice, diagnosis, or treatment recommendations, and does not create a doctor-patient relationship between the reader and Life Clinical Research or any of its staff. Medical circumstances vary between individuals — always seek advice from a qualified healthcare professional before making decisions about health, treatment, or participation in clinical research. Life Clinical Research accepts no responsibility for actions taken based on this content.