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Home › Conditions › Heart Failure with Preserved Ejection Fraction

Heart Failure with Preserved Ejection Fraction

Part of Heart Failure

14 published articles · Updated continuously

Clinical Trial Landscape

Clinical Trials for Heart Failure with Preserved Ejection Fraction

23 trials tracked for Heart Failure with Preserved Ejection Fraction: 11 in phase 3 or 4 and 8 with published results. The most-cited published study has 163 citations.

23Trials tracked
11Phase 3 & 4
0Recruiting
8With published results
Phase distribution
Phase 4 4 Phase 3 7 Phase 2 9 Phase 1 1 Other / NA 2
  1. Phase 3 A Randomized, Double-blind Controlled Study Comparing LCZ696 to Medical Therapy for Comorbidities in HFpEF Patients Completed · 163 cited
  2. Phase 3 A Study of Tirzepatide (LY3298176) in Participants With Heart Failure With Preserved Ejection Fraction (HFpEF) and Obesity: The SUMMIT Trial Completed · 145 cited
  3. Phase 3 Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction Completed · 97 cited
  4. Phase 3 DETERMINE-preserved - Dapagliflozin Effect on Exercise Capacity Using a 6-minute Walk Test in Patients With Heart Failure With Preserved Ejection Fraction Completed · 54 cited
  5. Phase 3 Study to Evaluate the Efficacy and Safety of AZD4831 in Participants With Heart Failure With Left Ventricular Ejection Fraction > 40% Completed · 44 cited
  6. Phase 3 Changes in NT-proBNP, Safety, and Tolerability in HFpEF Patients With a WHF Event (HFpEF Decompensation) Who Have Been Stabilized and Initiated at the Time of or Within 30 Days Post-decompensation (PARAGLIDE-HF) Completed · 26 cited
Show 17 more trials
  1. Phase 3 Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure. Completed · 14 cited
  2. Phase 4 BLOCKade of Calcium Channels and Beta Adrenergic Receptors for the Treatment of Hypertension in HFpEF Completed
  3. Phase 4 Circulating NEP and NEP Inhibition Study in Heart Failure With Preserved Ejection Fraction Completed
  4. Phase 4 Impact of Beta-blockers on Physical Function in HFpEF Completed
  5. Phase 4 Pilot Deprescribing N-of-1 Trials for Beta-blockers in HFpEF Completed
  6. Phase 2 Study of Verinurad in Heart Failure With Preserved Ejection Fraction Completed
  7. Phase 2 Developing Oral LT3 Therapy for Heart Failure - HFpEF Completed
  8. Phase 2 Cilostazol for HFpEF Completed
  9. Phase 2 Acute Effects of Exogenous Ketone Ester Administration in Heart Failure Completed
  10. Phase 2 A Study to Evaluate Whether Macitentan is an Effective and Safe Treatment for Patients With Heart Failure With Preserved Ejection Fraction and Pulmonary Vascular Disease Completed
  11. Phase 2 A Study of Mavacamten in Participants With HFpEF and Elevation of NT-proBNP With or Without Elevation of cTnT Completed
  12. Phase 2 Acute Effects of Inorganic Nitrite on Cardiovascular Hemodynamics in Heart Failure With Preserved Ejection Fraction Completed
  13. Phase 2 A Study of the Effect of IW-1973 on the Exercise Capacity of Patients With Heart Failure With Preserved Ejection Fraction (HFpEF) Completed
  14. Phase 2 Dapagliflozin (DAPA) Effects in HFpEF Completed
  15. Phase 1 Pressure Assessment to Improve Outcomes After TAVR: a Registry Completed
  16. N/A The Effects of Ranolazine on Exercise Capacity in Patients With Heart Failure With Preserved Ejection Fraction Completed
  17. N/A Heart Function in Patients Assessed for Sleep Apnoea Completed

Showing the 23 most-cited and recently-updated of 23 trials. Browse the full registry →

Trial data sourced from ClinicalTrials.gov. Counts describe the research landscape and are not a treatment recommendation. Informational only — not medical advice.

What the trials found Updated — new results For clinicians

Heart Failure with Preserved Ejection Fraction: what the trials found

New evidence indicates that Amlodipine Besylate significantly reduces home systolic blood pressure in patients with Heart Failure with Preserved Ejection Fraction (HFpEF) 1. However, it did not show a statistically significant effect on home diastolic or office systolic blood pressure 1.

Tirzepatide demonstrated significant clinical benefits in HFpEF, including a reduction in the first occurrence of heart failure outcomes (p=0.026), improved exercise capacity as measured by 6-minute walk distance (p<0.001), and a significant reduction in body weight 6.

Sacubitril/valsartan was shown to significantly reduce NT-proBNP levels at week 12 5 and week 8 10. In a large trial, LCZ696 showed a significant improvement in NYHA functional class at month 8 7.

Dapagliflozin demonstrated significant improvements in physiological markers including reduced pulmonary capillary wedge pressure (PCWP) at both rest and maximal exercise, as well as weight loss 16. In a large-scale trial, Dapagliflozin significantly reduced the composite endpoint of cardiovascular death or heart failure hospitalization/urgent visits 11.

Recent results — preliminary, needs further review

  • mavacamten showed a reduction in NT-proBNP and high-sensitivity cardiac troponin T levels at week 26 (not yet corroborated)
  • Nitrite was associated with lower exercise pulmonary capillary wedge pressure and changes in central pressures (not yet corroborated)

For the clinician treating this condition

  • Amlodipine Besylate may be utilized for blood pressure management specifically targeting systolic pressure in HFpEF patients.
  • Tirzepatide is associated with significant weight loss and improved exercise capacity in the HFpEF population.
  • Sacubitril/valsartan (LCZ696) effectively reduces NT-proBNP levels and improves NYHA functional classification.
  • Dapagliflozin provides evidence of reduced heart failure hospitalizations and improvements in pulmonary wedge pressures.

AI synthesis of 7 cited trials, updated Jun 29, 2026. Informational only — not medical advice; trial data sourced from ClinicalTrials.gov. How we use AI.

HCP Mode — summaries include clinical detail, trial data, and statistical outcomes.
Patient Mode — summaries use plain language, avoiding clinical jargon.
Unified cardiometabolic disease framework links T2DM, ASCVD, HFpEF, MASLD, hypertension, and CKD via shared pathophysiology
Cardiology Guideline
Unified cardiometabolic disease framework links T2DM, ASCVD, HFpEF, MASLD, hypertension, and CKD via shared pathophysiology New Framework Links Heart and Kidney Health in Diabetes
This guideline provides a narrative review of the unified cardiometabolic disease (UCD) continuum. It argues that conditions like T2DM, ASCV…
Experts suggest that diabetes, heart failure, and kidney disease may share a single underlying cause rather than being separate conditions.
Frontiers Jul 19, 2026
GLP-1 receptor agonists reduce HF worsening events in HFpEF but show no benefit in HFrEF
Cardiology Meta-analysis
GLP-1 receptor agonists reduce HF worsening events in HFpEF but show no benefit in HFrEF GLP-1 drugs help heart failure with preserved ejection fraction
This meta-analysis of 11,234 patients with heart failure (HFpEF and HFrEF) found that GLP-1 receptor agonists significantly reduced HF worse…
GLP-1 receptor agonists improve outcomes in heart failure with preserved ejection fraction but not in reduced ejection fraction, according t…
Jul 15, 2026
Beta-blocker use associated with lower mortality risk in heart failure with preserved ejection fraction
Cardiology Meta-analysis
Beta-blocker use associated with lower mortality risk in heart failure with preserved ejection fraction Beta-Blockers Linked to Lower Mortality in Heart Failure Patients
This meta-analysis of observational studies found that beta-blocker use was associated with lower all-cause and cardiovascular mortality in …
A large study of over 400,000 patients suggests that beta-blocker use is linked to lower death rates for those with a specific type of heart…
Jul 1, 2026
SGLT2 inhibitors provide robust prognostic benefits in heart failure with inconsistent results in post-myocardial infarction settings
Cardiology Sys. Review
SGLT2 inhibitors provide robust prognostic benefits in heart failure with inconsistent results in post-myocardial infarction settings SGLT2 inhibitors show promise for heart failure and diabetes
This narrative review examines the cardiovascular and metabolic effects of SGLT2 inhibitors, specifically empagliflozin and dapagliflozin. T…
New evidence shows how SGLT2 inhibitors may protect the heart and manage risks for patients with type 2 diabetes and heart failure.
Frontiers Jun 9, 2026
Meta-analysis of exercise rehabilitation for HFpEF shows mixed outcomes on mortality and rehospitalization
Cardiology Meta-analysis
Meta-analysis of exercise rehabilitation for HFpEF shows mixed outcomes on mortality and rehospitalization Exercise rehab lowers rehospitalization risk for heart failure patients
This systematic review and meta-analysis of 2,025 participants with HFpEF synthesized evidence on exercise-based cardiac rehabilitation. It …
A meta-analysis of 2,025 patients found exercise-based cardiac rehabilitation significantly reduced rehospitalization risk and improved walk…
Frontiers May 28, 2026
Network meta-analysis of finerenone and SGLT2 inhibitors in heart failure with preserved or mildly reduced ejection fraction
Drug Pipeline Meta-analysis
Network meta-analysis of finerenone and SGLT2 inhibitors in heart failure with preserved or mildly reduced ejection fraction New analysis shows finerenone and SGLT2 drugs help lower heart failure hospitalization risks for patients with preserved ejection fraction
This network meta-analysis evaluated finerenone, sodium–glucose cotransporter 2 inhibitors, renin–angiotensin system inhibitors, and angiote…
A large review of over 65,000 patients found that finerenone and SGLT2 inhibitors reduce hospital stays and worsening heart failure compared…
Frontiers May 15, 2026
Non-randomized preprint on dapagliflozin and epicardial adipose tissue in HFpEF
Cardiology
Non-randomized preprint on dapagliflozin and epicardial adipose tissue in HFpEF Dapagliflozin linked to fat loss in heart failure patients
This preprint reports a non-randomized clinical trial in 60 patients with left ventricular diastolic dysfunction.
Adding dapagliflozin to standard care reduced epicardial fat in a small group of heart failure patients, though this preprint study needs co…
Apr 28, 2026
Rule-based Clinical Decision Support System Matches Expert Assessments in Heart Failure With Preserved Ejection Fraction
Cardiology Cohort
Rule-based Clinical Decision Support System Matches Expert Assessments in Heart Failure With Preserved Ejection Fraction AI Helps Doctors Spot Heart Failure Faster
This prospective cohort study evaluated 134 patients with exertional dyspnea and preserved left ventricular ejection fraction.
A new AI tool helps doctors diagnose stiff heart failure faster by automating complex measurements during exercise tests with high accuracy.
Frontiers Apr 16, 2026
Combined NT-proBNP, DLK-1, PSP-D, and PCSK-9 detection shows moderate diagnostic performance for HFpEF
Cardiology Cohort
Combined NT-proBNP, DLK-1, PSP-D, and PCSK-9 detection shows moderate diagnostic performance for HFpEF New blood markers may help diagnose heart failure with preserved ejection fraction more accurately
This prospective biomarker cohort study evaluated 58 HFpEF patients and 30 healthy controls to assess the diagnostic utility of specific bio…
Mixing four blood markers improves heart failure diagnosis accuracy compared to standard tests alone, offering a clearer path to early detec…
Frontiers Apr 16, 2026
Spironolactone reduces cardiovascular events in HFpEF patients with increased LV mass or left atrial volume
Cardiology RCT
Spironolactone reduces cardiovascular events in HFpEF patients with increased LV mass or left atrial volume Spironolactone Saves Lives in Specific Heart Failure Types
This post hoc analysis of the TOPCAT randomized controlled trial evaluated spironolactone in 757 participants with heart failure with preser…
Spironolactone cuts death risk for heart failure patients with enlarged heart chambers, proving that heart size matters just as much as pump…
Apr 12, 2026
HFpEF probability scores rule out disease but show limitations in AF and obesity phenotypes
Cardiology Sys. Review
HFpEF probability scores rule out disease but show limitations in AF and obesity phenotypes HFpEF probability scores work well for typical cases but struggle with atrial fibrillation and obesity
This systematic review evaluated the performance of HFpEF probability scores (HFA-PEFF and H2FPEF) in patients with heart failure with prese…
Heart failure scores work well for typical cases but lose accuracy in patients with atrial fibrillation or obesity due to altered biological…
Frontiers Apr 9, 2026
Network meta-analysis of pharmacotherapies shows GLP-1 RAs and SGLT2is reduce composite cardiovascular death and hospitalization in HFpEF
Cardiology Meta-analysis
Network meta-analysis of pharmacotherapies shows GLP-1 RAs and SGLT2is reduce composite cardiovascular death and hospitalization in HFpEF New drugs may lower heart failure risk and improve walking distance for patients with preserved ejection fraction
This network meta-analysis evaluated 48,235 patients with heart failure with preserved ejection fraction (HFpEF) treated with various pharma…
New heart drugs lower death risk and hospital visits for patients with preserved ejection fraction while improving walking distance.
Apr 6, 2026

Research across Heart Failure

Related studies from across the Heart Failure family.

Higher serum total bilirubin levels associated with lower long-term risk in coronary heart disease patients
Cardiology Meta-analysis
Higher serum total bilirubin levels associated with lower long-term risk in coronary heart disease patients High bilirubin levels linked to lower heart risk in some cases
This meta-analysis examined the association between serum total bilirubin and major adverse cardiovascular events in patients undergoing per…
New data suggests high bilirubin might protect patients with coronary heart disease from long-term risks, though the evidence is still early…
Frontiers Jul 30, 2026
GLP-1 receptor agonists and tirzepatide provide cardiovascular benefits across multiple clinical scenarios
Diabetes & Endocrinology Sys. Review
GLP-1 receptor agonists and tirzepatide provide cardiovascular benefits across multiple clinical scenarios Incretin Drugs Show Heart Benefits Across Multiple Conditions
This state-of-the-art review synthesizes evidence regarding incretin analogues, specifically GLP-1 receptor agonists and tirzepatide. The re…
GLP-1 drugs and tirzepatide prove heart benefits in diabetes, obesity, heart failure, and more.
Frontiers Jul 25, 2026
Targeting protein acylation modifications via SIRT1 and HDACs may mitigate myocardial injury and inflammation
Drug Pipeline Sys. Review
Targeting protein acylation modifications via SIRT1 and HDACs may mitigate myocardial injury and inflammation New ways to treat heart failure through protein modifications
This narrative review explores how protein acylation modifications, including acetylation and lactylation, regulate metabolic signaling in c…
Scientists identify how targeting specific protein changes can help repair heart tissue and reduce inflammation in patients with heart disea…
Frontiers Jul 25, 2026
Percutaneous transcatheter closure using an Amplatzer Muscular VSD Occluder treats left ventricular pseudoaneurysm
Cardiology Guideline
Percutaneous transcatheter closure using an Amplatzer Muscular VSD Occluder treats left ventricular pseudoaneurysm Transcatheter Closure Shows Promise for Heart Failure Patients
This case report describes a 75-year-old male with heart failure and a left ventricular pseudoaneurysm successfully treated via percutaneous…
A new procedure using a transcatheter occluder may offer a safe way to treat heart failure caused by a specific heart wall defect.
Frontiers Jul 23, 2026
Remote cardiac rehabilitation supported by mHealth improves exercise capacity in patients with heart failure
Cardiology Meta-analysis
Remote cardiac rehabilitation supported by mHealth improves exercise capacity in patients with heart failure Virtual cardiac rehab improves exercise capacity for heart failure patients
Researchers evaluated the impact of structured, remote, and hybrid cardiac rehabilitation programs compared to usual care or center-based mo…
Remote and hybrid heart rehabilitation programs using mobile health tools can improve walking distance and oxygen use in people with heart f…
Jul 22, 2026
Neural-immune-cardiovascular axis emerges as therapeutic target in atherosclerosis, hypertension, heart failure
Allergy & Immunology Sys. Review
Neural-immune-cardiovascular axis emerges as therapeutic target in atherosclerosis, hypertension, heart failure New pathways link nerves and immunity in heart disease
This systematic review synthesizes evidence on the neural-immune-cardiovascular axis in cardiovascular homeostasis and pathogenesis. It exam…
Scientists are mapping how the connection between your nervous system and immune cells may drive conditions like high blood pressure and hea…
Frontiers Jul 22, 2026
Cognitive impairment affects 39% of chronic heart failure patients in pooled analysis
Cardiology Meta-analysis
Cognitive impairment affects 39% of chronic heart failure patients in pooled analysis Heart Failure Patients Face High Risk of Cognitive Impairment
This meta-analysis of 14 studies (5,127 patients) reports a pooled cognitive impairment prevalence of 39.3% in chronic heart failure. Risk f…
Nearly 40% of people with chronic heart failure experience cognitive impairment, with specific factors like age and depression increasing th…
Frontiers Jul 20, 2026
Persistent insomnia in heart failure is associated with higher anxiety and lower functional capacity
Cardiology RCT
Persistent insomnia in heart failure is associated with higher anxiety and lower functional capacity Persistent insomnia linked to higher anxiety in heart failure patients
This secondary analysis of a randomized trial involving 400 patients with heart failure identified distinct insomnia trajectories over 12 mo…
A new look at heart failure data shows that lasting sleep issues are tied to higher anxiety and lower physical ability.
Jul 16, 2026
MAGGIC Score Predicts Mortality Outcomes in Patients Undergoing Mitral Valve Transcatheter Edge to Edge Repair
Cardiology Meta-analysis
MAGGIC Score Predicts Mortality Outcomes in Patients Undergoing Mitral Valve Transcatheter Edge to Edge Repair New scoring system helps predict heart failure surgery risks
The MAGGIC score demonstrates significant predictive value for mortality in patients with functional or degenerative mitral regurgitation af…
A new risk score accurately predicts death rates for patients undergoing specific heart valve repairs, outperforming several standard models…
Jul 12, 2026
Patients with cardiovascular diseases show measurable prevalence of active cancer across multiple conditions
Cardiology Sys. Review
Patients with cardiovascular diseases show measurable prevalence of active cancer across multiple conditions Heart disease patients show measurable risk of developing various cancers
This systematic review and meta-analysis analyzed 4,759,695 patients to determine the prevalence of active cancer in individuals with variou…
New data shows that people with heart conditions like stroke or heart failure have a measurable rate of active cancer cases.
medRxiv Jul 9, 2026
Macrophage migration inhibitory factor serves as a potential biomarker and therapeutic target for atrial fibrillation
Cardiology Sys. Review
Macrophage migration inhibitory factor serves as a potential biomarker and therapeutic target for atrial fibrillation Protein levels may predict heart failure and stroke risks
This systematic review synthesizes evidence regarding macrophage migration inhibitory factor (MIF) in the context of atrial fibrillation and…
A specific protein called MIF is linked to heart damage and can help doctors predict serious complications like stroke or heart failure.
Frontiers Jul 9, 2026
Health literacy is moderately associated with improved self-care behaviors in patients with multiple chronic diseases
Primary Care & Family Medicine Meta-analysis
Health literacy is moderately associated with improved self-care behaviors in patients with multiple chronic diseases Better health literacy helps people manage chronic diseases more effectively
This meta-analysis of 138 studies found a moderate positive association (r = 0.29, 95% CI: 0.26-0.31) between health literacy and self-care …
Understanding medical information and using digital tools can help people with chronic conditions like diabetes or heart failure manage thei…
Jul 7, 2026

Questions about Heart Failure with Preserved Ejection Fraction

Do GLP-1 drugs and SGLT2 inhibitors reduce hospital visits for my heart failure?

Yes, both GLP-1 receptor agonists and SGLT2 inhibitors reduce hospital visits for heart failure with preserved ejection fraction (HFpEF), according to a large network meta-analysis and other studies.

Full answer →
Does spironolactone lower my risk of heart problems if I have a large heart?

Yes, spironolactone may lower your risk of heart problems if you have a large heart, especially reducing heart failure hospitalizations and cardiovascular death.

Full answer →

All Heart Failure with Preserved Ejection Fraction Articles