What are the recommendations from the American Society of Echocardiography (ASE) guideline from July 2025 for the treatment of heart failure with preserved ejection fraction (HFpEF)?

ASE Guideline July 2025: HFpEF Management

I cannot provide specific recommendations from an "ASE guideline from July 2025" as this guideline does not exist in the evidence provided. However, I can provide the most current evidence-based recommendations for HFpEF diagnosis and treatment based on available guidelines.

Current Guideline-Directed Medical Therapy for HFpEF

The cornerstone of HFpEF pharmacotherapy now includes SGLT2 inhibitors as first-line disease-modifying therapy, with additional agents selected based on specific patient characteristics. 1

Primary Pharmacological Recommendations

SGLT2 Inhibitors (First-Line)

• Empagliflozin or dapagliflozin should be initiated in all patients with HFpEF to reduce cardiovascular death and heart failure hospitalizations. 1, 2, 3
• These agents demonstrate benefit regardless of diabetes status and across the ejection fraction spectrum. 2, 3

Mineralocorticoid Receptor Antagonists (MRAs)

• MRAs are recommended as part of guideline-directed medical therapy to reduce morbidity and mortality. 1
• Consider particularly in patients with adequate renal function and normal potassium levels. 1

Angiotensin Receptor-Neprilysin Inhibitors (ARNIs)

• ARNIs may be considered for selected patients with HFpEF, though evidence shows smaller reductions in HF hospitalizations compared to HFrEF. 1, 4
• Use when other therapies are insufficient or in specific phenotypes. 2

Angiotensin Receptor Blockers (ARBs)

• ARBs are included in the therapeutic armamentarium for HFpEF management. 1

Diuretics

• Loop diuretics should be used judiciously as needed to reduce congestion and improve symptoms, not as disease-modifying therapy. 1

Beta-Blockers: Specific Indications Only

• Beta-blockers are NOT routinely recommended for HFpEF unless specific indications exist: prior myocardial infarction (up to 3 years), angina, or atrial fibrillation. 1
• Monitor exercise tolerance due to potential chronotropic incompetence. 1

Diagnostic Approach: Echocardiographic Criteria

The diagnosis of HFpEF requires an integrated assessment of multiple echocardiographic parameters—no single parameter is sufficient. 5

Mandatory Diagnostic Components

Three Core Requirements 5

• Preserved LV systolic function (LVEF ≥45-50%)
• Evidence of diastolic dysfunction
• Structural or functional cardiac abnormalities

Key Structural Parameters to Assess

Five Essential Measurements 5

• Left atrial volume index (LAVI): Typically elevated, reflecting chronic elevation of filling pressures
• Left ventricular mass index (LVMI): Often increased, indicating LV hypertrophy
• Left ventricular hypertrophy: Direct assessment
• Tricuspid regurgitation velocity (TRV): Assesses pulmonary pressures
• Pulmonary artery pressure: Elevated in many HFpEF patients

Diastolic Function Assessment

E/e' Ratio (Most Validated Parameter) 1, 5

• E/e' >15 indicates high filling pressures
• E/e' <8 suggests low filling pressures
• Pooled correlation with invasive filling pressures: r=0.56 (modest but best available)
• Prognostic value: HR 1.05 per unit increase for mortality/cardiovascular hospitalization

E/A Ratio Patterns 5

• Impaired relaxation pattern
• Restrictive filling pattern
• Pseudonormal pattern

Additional Doppler Indices 5

• Pulmonary vein flow
• (A mitral - A pulmonary) duration
• Flow propagation velocity (Vp)
• E/Vp ratio

Critical Diagnostic Pitfall: Exclude HFpEF Mimics

Before confirming HFpEF diagnosis, systematically exclude specific mimics that require different treatment approaches. 1

High-Priority Mimics to Rule Out

Cardiac Amyloidosis 1

• Clinical clues: Increased LV wall thickness, carpal tunnel syndrome, lumbar spinal stenosis, neuropathy
• Testing: Monoclonal protein screen (serum/urine immunofixation electrophoresis and serum free light chains), technetium pyrophosphate scan, endomyocardial biopsy if monoclonal protein positive

Hypertrophic Cardiomyopathy 1

• Clinical clues: Unexplained LV hypertrophy, LV outflow tract obstruction, family history
• Testing: CMR if diagnosis uncertain on echocardiogram

Cardiac Sarcoidosis 1

• Clinical clues: Extracardiac disease (pulmonary, ocular, dermatologic), high-degree AV block (especially age <60), ventricular arrhythmias
• Testing: CMR, FDG-PET scan, tissue biopsy

Hemochromatosis 1

• Clinical clues: Family history or frequent blood transfusions, diabetes, erectile dysfunction
• Testing: Ferritin and transferrin, HFE genetic testing, CMR with T2* imaging

Fabry Disease 1

• Clinical clues: Angiokeratomas, sensory neuropathy, proteinuria
• Testing: Serum alpha-galactosidase level (in men), GLA genetic testing, biopsy

High-Output Heart Failure 1

• Clinical clues: 4-chamber enlargement and/or increased LV outflow tract VTI on echo
• Testing: Investigate underlying causes (anemia, arteriovenous malformations, cirrhosis, fistulas, thiamine deficiency)

Pericardial Disease 1

• Clinical clues: Prior cardiac surgery, chest radiation, or pericarditis; right-sided HF symptoms
• Testing: CMR, right and left heart catheterization demonstrating discordance in LV/RV pressure tracings during inspiration

Comorbidity Management: Essential Component

Aggressive management of comorbidities is mandatory as they directly contribute to symptoms, prognosis, and pathophysiology. 1

Priority Comorbidities to Address 1

• Hypertension
• Diabetes mellitus
• Obesity (weight reduction recommended)
• Atrial fibrillation
• Coronary artery disease
• Chronic kidney disease
• Obstructive sleep apnea

Non-Pharmacological Interventions

Supervised Exercise Training 2, 3

• Recommended to improve symptoms and functional capacity
• Should be incorporated into comprehensive management

Weight Reduction for Obesity 2, 3

• Specifically recommended for obese patients with HFpEF
• Glucagon-like peptide-1 receptor agonists show emerging promise in this phenotype 2

Sex-Specific Considerations

Women comprise the majority of HFpEF patients and have unique diagnostic and prognostic features. 1

Key Differences in Women 1

• Higher ejection fractions and more preserved LV global longitudinal strain compared to men
• Lifetime risk of HF approximately 20% by age 40, increasing to 30% by age 55
• History of pre-eclampsia increases risk for subsequent HFpEF hospitalization
• Pregnancy history should be systematically obtained

Phenotype-Guided Approach

HFpEF is a heterogeneous syndrome requiring phenotype-specific treatment strategies beyond LVEF categorization. 4, 2, 6

Recognized Clinical Phenotypes 6

• Lung congestion predominant
• Chronotropic incompetence
• Pulmonary hypertension
• Skeletal muscle weakness
• Metabolic syndrome phenotype (particularly responsive to SGLT2i and GLP-1 agonists) 2

Prognostic Insight

• As LVEF increases, the proportion of hospitalizations and deaths due to cardiac causes decreases, reflecting the burden of non-cardiac comorbidities. 4
• Non-cardiovascular death is common in HFpEF patients. 3

When to Refer to Specialist

Refer to cardiologist or heart failure specialist when: 1

• Diagnosis remains uncertain after initial evaluation
• Need for advanced diagnostic testing (exercise echocardiography, invasive hemodynamics)
• Suspected HFpEF mimics requiring specialized workup
• Inadequate response to initial GDMT
• Complex comorbidity management