NEW TREATMENTS FOR HEART FAILURE WITH PRESERVED EJECTION FRACTION - Heart failure treatment update

Sep 29, 2026

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Heart failure with preserved ejection fraction (HFPEF) represents about half of all new heart failure diagnoses. Prior to 2022, loop diuretics were the primary treatment for symptom relief. Since then, multiple therapies designed for other indications have shown benefit, including SGLT2 inhibitors with class 1 recommendations, GLP-1–based agents improving symptoms and functional capacity, and finerenone and mavacamten reducing heart-failure-related risk and disease markers. Evidence to date does not show reduced mortality, but expanding data suggests future therapeutic gains.

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Game Changers

New treatments for HFPEF

Relationship to prior HFREF evidence

Authors and correspondence

References

Ulster Med J 2025;94(3):151 Game Changers NEW TREATMENTS FOR HEART FAILURE WITH PRESERVED EJECTION FRACTION Heart failure with preserved ejection fraction (HFPEF) accounts for about half of all new heart failure diagnoses. Until 2022 the only treatment was loop diuretics for symptom relief. In the short time since, several new therapeutic options have emerged, all of which were initially designed for other clinical indications: 1. Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been used in diabetic patients since 2012. In 2022 two major trials in HFPEF patients showed that both dapagliflozin and empagliflozin substantially reduce the risk of hospitalization, resulting in a Class 1 recommendation for both agents for the treatment of HFPEF.1 2. Glucagon-like peptide-1 (GLP-1) analogues have been used in diabetic patients for 20 years and are now very familiar to the public because of their off-label use by celebrities who want to lose weight. Semaglutide has been shown to improve symptoms, exercise capacity and weight loss in patients with obesity and HFPEF while substantially reducing NT-proBNP levels2,3 . Tirzepatide, a dual agonist of GLP-1 and glucose-dependent insulinotropic polypeptide receptors, also significantly improves symptoms in patients with obesity and HFPEF, while reducing the likelihood of a worsening heart failure event.4 3. Finerenone, a nonsteroidal mineralocorticoid receptor antagonist was initially developed to reduce the risk of renal complications in type 2 diabetes. It has subsequently been shown to reduce the risk of heart failure events in patients with HFPEF5 and it is now licensed to treat the condition in the United States of America. 4. Mavacamten, a cardiac myosin inhibitor, substantially reduces left ventricular outflow tract obstruction in patients with hypertrophic cardiomyopathy. In a phase 2 trial, mavacamten improved echocardiographic markers of LV diastolic function and reduced plasma NT-proBNP and troponin levels in patients with HFPEF 6. A phase 3 randomised clinical trial is underway. Outcomes for patients with heart failure with reduced ejection fraction (HFREF) have improved dramatically with the emergence of“four pillars” of evidence-based treatment. So far none of the new HFPEF treatments has reduced mortality but the accumulation of evidence above predicts a similar enhancement of therapeutic options for this growing population of patients. Dr Zubair Ahamed & Dr Niall Herity Cardiology Department, Belfast Health and Social Care Trust, Northern Ireland Corresponding Author: Dr Niall Herity, [Consultant Cardiologist: Niall.Herity@belfasttrust.hscni.net](Consultant Cardiologist: Niall.Herity@belfasttrust.hscni.net) REFERENCES: 1. McDonagh TA, Metra M, Adamo M, Gardner RS, BaumbachA, Burr H, et al. 2023 Focused Update of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2023; 44(37): 3627–39. 2. Kosiborod MN, Abildstrøm SZ, Borlaug BA, Butler J, Rasmussen S, Davies M, et al. Semaglutide inpatients with heart failure with preserved ejection fraction and obesity. NEngl J Med.2023; 389(12): 1069–84. 3. Kosiborod MN, Petrie MC, BorlaugBA, Butler J, Davies MJ, Hovingh GK, et al. Semaglutide inpatients with obesity-related heart failure and type 2 diabetes. NEngl J Med. 2024; 390(15): 1394–407. 4. Packer M, Zile MR, Kramer CM, Baum SJ, Litwin SE, MenonV, et al. Tirzepatide for heart failure with preserved ejection fraction and obesity. NEngl J Med. 2025; 392(5): 427-37. 5. Solomon SD, McMurray JJV, Vaduganathan M, Claggett B, Jhund PS, Desai AS, et al. Finerenone in heart failure with mildly reduced or preserved ejection fraction. NEngl J Med. 2024; 391(16): 1475–85. 6. Shah SJ, Rigolli M, JavidialsaadiA, Patel RB, Khadra S, Goyal P, et al. Cardiac myosin inhibition in heart failure with normal and supranormal ejection fraction: primary results of the EMBARK-HFpEF Trial. JAMA Cardiol. 202

FAQs

What proportion of new heart failure diagnoses involve HFPEF?

HFPEF accounts for about half of all new heart failure diagnoses.

Which therapies have shown class 1 recommendations for HFPEF?

Dapagliflozin and empagliflozin (SGLT2 inhibitors) have class 1 recommendations for HFPEF based on major 2022 trials.

Do the new HFPEF treatments reduce mortality so far?

So far, none of the new HFPEF treatments has reduced mortality, although accumulated evidence suggests improved therapeutic options for this growing population.

Sep 29, 2026

Uploaded by dabgoudw