Guidelines for Heart Failure with Preserved LVEF (≥50%)

Recommendations for Patients With Preserved LVEF (≥50%): A Practical Guide to HFpEF Treatment

Heart failure with preserved ejection fraction (HFpEF) is an increasingly recognized form of heart failure in which patients have symptoms and signs of heart failure despite a relatively preserved left ventricular ejection fraction. According to the 2022 AHA/ACC/HFSA Heart Failure Guideline, HFpEF is defined as heart failure with an LVEF ≥50% together with evidence supporting increased left ventricular filling pressures. 

Unlike HFrEF, where several therapies have established mortality benefits, treatment of HFpEF has historically focused on controlling congestion, blood pressure, atrial fibrillation, ischemic heart disease and other associated conditions. However, the therapeutic landscape has changed substantially, particularly with the introduction of SGLT2 inhibitors.

The 2022 AHA/ACC/HFSA guideline provides a practical framework for the treatment of symptomatic patients with HFpEF.

TREATMENT OF HFpEF

For patients with symptomatic heart failure and LVEF ≥50%, the major pharmacological options highlighted in the guideline are:

• Diuretics as needed • SGLT2 inhibitors – Class 2a • Angiotensin receptor-neprilysin inhibitor (ARNi) – Class 2b • Mineralocorticoid receptor antagonists (MRAs) – Class 2b • Angiotensin receptor blockers (ARBs) – Class 2b

The potential benefit of ARNi, MRA and ARB therapy appears to be greater in patients whose LVEF is closer to the lower end of the preserved-EF range. 

1. DIURETICS – AS NEEDED

Diuretics remain an important component of HFpEF management, particularly when patients have clinical evidence of volume overload.

Patients with HFpEF may develop:

• Peripheral edema • Pulmonary congestion • Elevated jugular venous pressure • Dyspnea • Orthopnea • Weight gain due to fluid retention

Loop diuretics are commonly used when significant congestion is present.

The primary role of diuretics in HFpEF is symptom relief and decongestion rather than modification of long-term disease progression.

Treatment should therefore be individualized according to the patient's volume status. Excessive diuresis may result in hypotension, renal dysfunction and electrolyte abnormalities.

A practical principle is:

Congested patient → diuretic therapy

Euvolemic patient → avoid unnecessary escalation of diuretics

The 2022 guideline specifically recommends diuretics for patients with HF and fluid retention to relieve congestion and improve symptoms. 

2. SGLT2 INHIBITORS – CLASS 2a

One of the most important changes in HFpEF treatment is the introduction of sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors).

Examples include:

• Empagliflozin • Dapagliflozin

The 2022 AHA/ACC/HFSA guideline gives SGLT2 inhibitors a Class 2a recommendation in HFpEF.

Importantly, the benefit of SGLT2 inhibitors in heart failure is not restricted to patients with diabetes.

This is particularly relevant because HFpEF frequently occurs in patients with multiple metabolic and cardiovascular comorbidities, including hypertension, obesity, diabetes and chronic kidney disease.

Evidence from EMPEROR-Preserved demonstrated a reduction in the composite of cardiovascular death or heart failure hospitalization with empagliflozin in symptomatic patients with LVEF >40%. The reduction was driven predominantly by fewer heart failure hospitalizations, while the reduction in cardiovascular death alone was not statistically significant. 

The DELIVER trial subsequently provided additional evidence supporting dapagliflozin in patients with HF with mildly reduced or preserved EF, showing a reduction in worsening heart failure or cardiovascular death. 

Therefore, SGLT2 inhibitors have become an important component of contemporary HFpEF management.

3. ARNi – CLASS 2b

Angiotensin receptor-neprilysin inhibition with sacubitril/valsartan may be considered in selected patients with HFpEF.

The 2022 guideline assigns ARNi a Class 2b recommendation.

The rationale is particularly relevant for patients with LVEF at the lower end of the preserved range.

The PARAGON-HF trial evaluated sacubitril/valsartan versus valsartan in patients with HFpEF. The trial did not achieve statistical significance for its primary composite endpoint of cardiovascular death and total heart failure hospitalizations. However, subsequent analyses suggested potentially greater benefit in certain subgroups, including patients with LVEF closer to the lower end of the preserved-EF range. 

Therefore, ARNi should not be viewed as a universal therapy for every patient with HFpEF. Its use should be individualized based on factors such as:

• LVEF • Blood pressure • Renal function • Potassium level • Presence of hypertension • Overall cardiovascular risk

4. MINERALOCORTICOID RECEPTOR ANTAGONISTS – CLASS 2b

MRAs such as spironolactone may be considered in selected patients with HFpEF.

The guideline assigns MRA therapy a Class 2b recommendation.

The evidence supporting MRAs in HFpEF is less robust than the evidence for their use in HFrEF.

In patients being considered for MRA therapy, renal function and serum potassium should be assessed before treatment and monitored during therapy.

MRAs may be particularly relevant in patients with HFpEF who have:

• Hypertension • Evidence of congestion • LVEF closer to 50% • Other clinical characteristics suggesting potential benefit

The potential risks include:

• Hyperkalemia • Worsening renal function • Hypotension • Gynecomastia with spironolactone

Careful patient selection and laboratory monitoring are therefore important.

5. ARBs – CLASS 2b

Angiotensin receptor blockers remain another therapeutic option for selected patients with HFpEF.

The 2022 guideline provides a Class 2b recommendation for ARBs.

ARBs may be particularly useful when treatment of hypertension is also required.

Examples include:

• Losartan • Valsartan • Candesartan • Irbesartan • Telmisartan

The choice of an ARB should be individualized according to blood pressure, renal function, potassium level, comorbidities and previous medication tolerance.

6. BLOOD PRESSURE CONTROL IS ESSENTIAL

HFpEF is strongly associated with hypertension.

Long-standing hypertension can result in:

• Left ventricular hypertrophy • Increased LV stiffness • Impaired ventricular relaxation • Increased LV filling pressures • Left atrial enlargement • Atrial fibrillation • Eventually, symptomatic HFpEF

Therefore, management of hypertension is a fundamental component of HFpEF treatment.

The 2022 guideline recommends treating hypertension according to appropriate blood pressure guidelines. However, the optimal blood pressure target specifically for HFpEF is not definitively established. 

Importantly, treatment should avoid excessive blood pressure reduction that may worsen renal function, cause hypotension or impair exercise tolerance.

7. MANAGEMENT OF ATRIAL FIBRILLATION

Atrial fibrillation is extremely common in HFpEF.

The relationship is bidirectional:

HFpEF → atrial enlargement and atrial fibrillation

Atrial fibrillation → loss of atrial contraction, increased filling pressures and worsening HF symptoms

Loss of atrial contraction can be particularly important in patients with a stiff, noncompliant left ventricle.

Management of atrial fibrillation may therefore improve symptoms and overall clinical status.

Management should include consideration of:

• Rate control • Rhythm control • Stroke prevention according to thromboembolic risk • Treatment of contributing factors • Management of hypertension, obesity and sleep apnea where appropriate

The 2022 guideline includes management of atrial fibrillation as an important component of HFpEF care. 

8. IDENTIFY AND TREAT COMORBIDITIES

HFpEF is not a single disease entity. It is a heterogeneous syndrome associated with multiple cardiovascular and systemic conditions.

Important associated conditions include:

• Hypertension • Diabetes mellitus • Obesity • Coronary artery disease • Chronic kidney disease • Atrial fibrillation • Valvular heart disease • Pulmonary hypertension • Sleep-disordered breathing • Cardiac amyloidosis

Successful HFpEF management therefore requires more than simply prescribing a heart failure medication.

9. THINK ABOUT CARDIAC AMYLOIDOSIS

Cardiac amyloidosis should be considered in selected patients with HFpEF, particularly when clinical or imaging features are suggestive.

Potential clues include:

• Increased LV wall thickness • Restrictive filling pattern • Biatrial enlargement • Low voltage on ECG despite increased LV wall thickness • Unexplained heart failure • Carpal tunnel syndrome • Peripheral neuropathy • Aortic stenosis with disproportionate LV thickening • Conduction disease

The 2022 guideline specifically emphasizes evaluation for cardiac amyloidosis in appropriate patients. 

10. CORONARY ARTERY DISEASE

Coronary artery disease is another important contributor to HFpEF.

Patients with symptoms suggestive of ischemia should undergo appropriate evaluation.

Management may include:

• Anti-ischemic therapy • Lipid-lowering therapy • Blood pressure control • Antiplatelet therapy when indicated • Revascularization when clinically appropriate

Treatment should be guided by the patient's overall cardiovascular risk and the presence of documented coronary disease.

11. HFpEF IS NOT SIMPLY “NORMAL EF”

An important clinical point is that preserved LVEF does not mean normal cardiac function.

A patient can have an LVEF of 60% and still have significant heart failure.

In HFpEF, the major abnormality may involve:

• LV relaxation • LV compliance • Filling pressures • Ventricular-arterial coupling • Left atrial function • Pulmonary pressures • Chronotropic response • Right ventricular function

Therefore, the diagnosis of HFpEF requires appropriate clinical assessment rather than relying on LVEF alone.

12. ROLE OF ECHOCARDIOGRAPHY IN HFpEF

Echocardiography plays a central role in the evaluation of suspected HFpEF.

Important echocardiographic parameters include:

• LVEF • LV mass and wall thickness • Left atrial volume • Mitral inflow velocities • E/A ratio • Tissue Doppler e′ velocity • E/e′ ratio • TR velocity • Pulmonary artery systolic pressure • Right ventricular function • Valvular disease

No single echocardiographic parameter should be interpreted in isolation.

The overall clinical picture, echocardiographic findings and, when appropriate, natriuretic peptide levels should be integrated to establish the diagnosis.

13. WHAT DO THE CLASS 2a AND 2b RECOMMENDATIONS MEAN?

Understanding the recommendation classes is important when interpreting the infographic.

Class 2a means:

The weight of evidence/opinion is in favor of usefulness, and the intervention is considered reasonable.

Class 2b means:

The usefulness of the intervention is less well established, and the treatment may be considered in selected patients.

Therefore, the therapies shown in the HFpEF treatment algorithm should not be interpreted as five mandatory medications that every patient must receive.

Instead, treatment should be individualized.

14. PRACTICAL HFpEF TREATMENT APPROACH

A practical approach to a patient with symptomatic HFpEF can be summarized as follows:

Step 1: Confirm the diagnosis

Establish that the patient has clinical heart failure and preserved LVEF, together with appropriate evidence of elevated filling pressures or other objective evidence supporting HFpEF.

Step 2: Assess volume status

If the patient is congested, use diuretics to achieve euvolemia.

Step 3: Consider an SGLT2 inhibitor

SGLT2 inhibitors have a Class 2a recommendation and can be considered regardless of diabetes status.

Step 4: Control blood pressure

Treat hypertension according to appropriate hypertension recommendations.

Step 5: Manage atrial fibrillation

Assess the need for rate control, rhythm control and anticoagulation according to the individual patient's clinical circumstances.

Step 6: Search for associated disease

Look for CAD, obesity, diabetes, CKD, valvular disease, pulmonary hypertension and other contributors.

Step 7: Consider ARNi, MRA or ARB in selected patients

These therapies have Class 2b recommendations, with potentially greater benefit in patients with LVEF closer to 50%.

Step 8: Reassess regularly

Monitor:

• Symptoms • Exercise capacity • Weight • Blood pressure • Renal function • Serum potassium • Volume status • Hospitalizations

KEY TAKE-HOME MESSAGES

HFpEF is defined in the 2022 AHA/ACC/HFSA guideline as heart failure with LVEF ≥50% and evidence of increased filling pressures.

Diuretics remain important for relieving congestion and improving symptoms.

SGLT2 inhibitors have a Class 2a recommendation in HFpEF and represent one of the most important advances in pharmacological management.

ARNi, MRA and ARB therapy may be considered in selected patients and carry Class 2b recommendations.

The potential benefit of ARNi, MRA and ARB therapy appears to be greater when LVEF is closer to 50%.

Hypertension should be actively treated.

Atrial fibrillation should be appropriately managed because it can substantially contribute to HFpEF symptoms.

Comorbidities such as obesity, diabetes, CKD, CAD, valvular disease and sleep-disordered breathing should be addressed.

Cardiac amyloidosis should be considered when clinical or imaging features raise suspicion.

HFpEF management is therefore a comprehensive strategy rather than simply prescribing a single heart failure medication.

CONCLUSION

The treatment of HFpEF has evolved significantly. The 2022 AHA/ACC/HFSA Heart Failure Guideline recognizes SGLT2 inhibitors as an important therapeutic option for symptomatic patients with preserved EF, while continuing to emphasize diuretics for congestion and individualized use of ARNi, MRAs and ARBs.

The most important practical principle is that HFpEF treatment should be phenotype-based and individualized. Controlling congestion, blood pressure and atrial fibrillation, identifying the underlying cause and treating associated cardiovascular and metabolic conditions are all essential components of care.

For patients with LVEF ≥50%, the modern HFpEF approach can therefore be remembered as:

DECONGEST → SGLT2 INHIBITOR → CONTROL BP → MANAGE AF → TREAT COMORBIDITIES → CONSIDER ARNi/MRA/ARB IN SELECTED PATIENTS

Reference: 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. 

The original guideline specifically notes that the greater potential benefit from ARNi, MRA and ARB therapy is seen in patients with LVEF closer to 50%.