Guideline-Directed Medical Therapy for Heart Failure with Preserved Ejection Fraction

Introduction to HFpEF Management

The American College of Cardiology recommends the initial approach to Guideline-Directed Medical Therapy (GDMT) for Heart Failure with Preserved Ejection Fraction (HFpEF) should focus on SGLT2 inhibitors as first-line therapy, followed by judicious use of diuretics for symptom management, and consideration of Mineralocorticoid Receptor Antagonists (MRAs), Angiotensin Receptor-Neprilysin Inhibitors (ARNIs), or Angiotensin Receptor Blockers (ARBs) based on specific patient characteristics 1, 2

The management of HFpEF focuses on risk stratification and comorbidity management, including hypertension 3, diabetes mellitus 1, obesity 3, atrial fibrillation 2, coronary artery disease 4, chronic kidney disease 3, and obstructive sleep apnea 1, 2
Nonpharmacological management includes exercise and weight loss 2 and consideration of wireless pulmonary artery monitoring in selected cases 1
Pharmacological therapy is used for symptom management and disease modification 1, 2

SGLT2 inhibitors are the first choice for most patients with HFpEF, with strong evidence from recent trials, including the DELIVER and EMPEROR-PRESERVED trials, demonstrating significant reductions in worsening HF events 4, HF hospitalizations 3, and composite of worsening HF and cardiovascular death 1, 2, 5
Diuretics should be used judiciously for symptom management and volume control, with loop diuretics being the mainstay for acute volume management 1, 2
MRAs, such as spironolactone, can be considered in appropriate patients, with benefit in reducing HF hospitalizations 1, 2
ARNIs, such as sacubitril/valsartan, can be considered in selected patients, particularly those with lower ejection fraction or women 1, 2
ARBs, such as candesartan, can be considered in selected patients, with modest benefit in the CHARM-PRESERVED trial 1, 2, 4

Beta-blockers are not recommended as primary HFpEF therapy unless specific indications exist, such as recent myocardial infarction, angina, or atrial fibrillation requiring rate control 1, 2, 4
A phenotype-guided approach can be considered, tailoring therapy based on predominant phenotypes, such as hypertensive 3 or atrial fibrillation 2

Regular assessment of volume status, renal function, and electrolytes is essential, especially with MRAs 3
Monitoring of symptoms and functional capacity is also crucial 2
Natriuretic peptide levels can be used to assess disease severity 4
Therapy should be adjusted based on clinical response and tolerability 1, 2