When should Empagliflozin (Empagliflozin) be used in patients with diastolic dysfunction?

Empagliflozin in Diastolic Dysfunction

Empagliflozin should be used in all patients with diastolic dysfunction, regardless of diabetes status, as it significantly improves diastolic function and reduces cardiovascular events. 1, 2

Evidence for Empagliflozin in Diastolic Dysfunction

Empagliflozin has demonstrated significant benefits in patients with diastolic dysfunction:

• The EmDia trial showed that empagliflozin 10 mg daily significantly decreased left ventricular E/e' ratio (a measure of diastolic function) by -1.18 compared to placebo (p<0.0001) after just 12 weeks of treatment 2
• This benefit was consistent across all subgroups, including patients with heart failure with preserved ejection fraction (HFpEF) 2
• The European Society of Cardiology and American College of Cardiology strongly recommend SGLT2 inhibitors, including empagliflozin, as first-line therapy for heart failure across all ejection fraction ranges 1

Dosing and Patient Selection

• Recommended dose: Empagliflozin 10 mg once daily 1
• eGFR considerations: Can be used in patients with eGFR ≥25 mL/min/1.73 m² 1
• Patient populations that benefit most:
  • Patients with LVEF >40% (particularly those with LVEF between 41-65%) 1
  • NYHA class II-III patients with frequent symptoms or hospitalizations 1
  • Patients with Type 2 diabetes and elevated left ventricular end-diastolic pressure 2

Mechanism of Action in Diastolic Dysfunction

Empagliflozin improves diastolic function through several mechanisms:

• Increases phospholamban (PLN) phosphorylation and SERCA2a/PLN ratio, enhancing cardiac relaxation 3
• Improves myocardial insulin sensitivity and glucose utilization 3
• Reduces blood pressure (both systolic and diastolic) 4
• Provides beneficial effects on vascular structure and function 5

Clinical Outcomes

Empagliflozin has demonstrated significant clinical benefits:

• 21% reduction in the composite outcome of cardiovascular death or hospitalization for heart failure (HR 0.79 [95% CI 0.69–0.90]; P < 0.001) 1
• Reduction in cardiovascular mortality 6, 1
• Benefits appear within weeks of initiation and are maintained long-term 1

Integration with Other Heart Failure Therapies

Empagliflozin should be added to standard guideline-directed medical therapy:

• Can be used alongside ACE inhibitors/ARBs/ARNI, beta-blockers, mineralocorticoid receptor antagonists, and diuretics 1
• Effectiveness is maintained regardless of background medical therapy 1
• May reduce the need for diuretic intensification 1
• May facilitate the use of mineralocorticoid receptor antagonists by reducing the risk of severe hyperkalemia 1

Monitoring and Safety Considerations

• Before initiation: Assess renal function and volume status 1
• Common adverse effects: Monitor for genital mycotic infections, urinary tract infections, and volume depletion/hypotension 1
• Rare but serious: Watch for euglycemic diabetic ketoacidosis 1
• Perioperative management: Withhold for at least 3 days before major surgery or procedures requiring prolonged fasting 1

Clinical Pearl

Unlike many other heart failure medications, empagliflozin requires no dose adjustment or up-titration, with benefits appearing within weeks of initiation. This makes it an excellent option for patients with diastolic dysfunction who may struggle with the complex titration schedules of other heart failure medications.