Will spironolactone improve grade 2 diastolic dysfunction?

Spironolactone for Grade 2 Diastolic Dysfunction

Spironolactone may improve diastolic function in patients with grade 2 diastolic dysfunction, particularly in those with heart failure with preserved ejection fraction (HFpEF) or mildly reduced ejection fraction (HFmrEF), but evidence for clinical outcome benefits is limited.

Evidence for Spironolactone in Diastolic Dysfunction

Guidelines Support for Specific Populations

The 2022 AHA/ACC/HFSA Heart Failure Guidelines provide the following recommendations:

• For patients with HFmrEF (LVEF 41-49%), mineralocorticoid receptor antagonists (MRAs) like spironolactone have a Class 2b recommendation (may be considered) 1
• For patients with HFpEF (with EF ≥45%, elevated BNP levels or HF admission within 1 year, eGFR >30 mL/min, creatinine <2.5 mg/dL, potassium <5.0 mEq/L), aldosterone receptor antagonists might be considered to decrease hospitalizations (Class 2b recommendation) 1

Mechanism of Action in Diastolic Dysfunction

Spironolactone may improve diastolic function through several mechanisms:

• Reducing cardiac fibrosis and promoting reverse remodeling 2
• Decreasing left ventricular mass index 3
• Improving neuroendocrine activation 3
• Antagonizing marinobufagenin, which plays a role in diastolic dysfunction 2

Clinical Trial Evidence

The Aldo-DHF trial specifically evaluated spironolactone in patients with heart failure with preserved ejection fraction:

• Spironolactone (25mg daily) improved diastolic function (E/e' decreased) compared to placebo over 12 months 3
• However, it did not improve maximal exercise capacity, patient symptoms, or quality of life 3
• Spironolactone induced reverse remodeling (reduced left ventricular mass index) 3

Another study in patients with hypertensive left ventricular hypertrophy found:

• Despite significant reduction in left ventricular mass index, short-term spironolactone therapy (6 months) did not lead to improvement in diastolic function 4

Patient Selection and Monitoring

Spironolactone should be considered in patients with:

• Grade 2 diastolic dysfunction with symptoms of heart failure
• Preserved or mildly reduced ejection fraction (≥45%)
• Adequate renal function (eGFR >30 mL/min, creatinine <2.5 mg/dL)
• Normal potassium levels (<5.0 mEq/L)

Dosing and Monitoring Protocol

1. Starting dose: 25 mg once daily 1
2. Check renal function and serum electrolytes before starting treatment
3. Re-check renal function and serum electrolytes at 1 and 4 weeks after starting treatment 1
4. Continue monitoring at 1,2,3, and 6 months after achieving maintenance dose

Important Precautions

Potential Adverse Effects

• Hyperkalemia (especially in patients with renal dysfunction or those taking ACE inhibitors/ARBs) 1
• Worsening renal function (reduction in eGFR) 3
• Gynecomastia in men (occurs in approximately 10% of patients) 1

When to Stop Therapy

Stop spironolactone immediately and monitor blood chemistry closely if:

• Serum potassium rises above 5.5 mmol/L
• Significant worsening of renal function occurs

Clinical Application Algorithm

1. Confirm diagnosis: Verify grade 2 diastolic dysfunction by echocardiography
2. Assess eligibility:
   • Check ejection fraction (ideally ≥45%)
   • Verify adequate renal function (eGFR >30 mL/min)
   • Check baseline potassium (<5.0 mEq/L)
3. Initiate therapy: Start spironolactone 25 mg once daily
4. Monitor closely: Follow electrolytes and renal function at weeks 1 and 4
5. Evaluate response: Reassess diastolic function parameters after 3-6 months

Conclusion

While spironolactone shows promise in improving diastolic function parameters in patients with grade 2 diastolic dysfunction, the clinical benefit in terms of symptoms, exercise capacity, and quality of life remains uncertain. The decision to use spironolactone should be based on careful patient selection, with particular attention to renal function and potassium levels.