Would a GLP-1 (Glucagon-like peptide-1) receptor agonist benefit patients with moderate concentric left ventricular hypertrophy (LVH)?

GLP-1 Receptor Agonists for Moderate Concentric LVH

GLP-1 receptor agonists may benefit patients with moderate concentric left ventricular hypertrophy (LVH) through multiple cardiovascular mechanisms, particularly in those with diabetes, obesity, or established cardiovascular disease, but caution is warranted in patients with heart failure with reduced ejection fraction (HFrEF). 1, 2

Mechanisms of Potential Benefit in LVH

• Reduction in epicardial adipose tissue: GLP-1 RAs have demonstrated significant reductions in epicardial adipose tissue thickness (up to 36% with liraglutide), which may be particularly beneficial in LVH 1
• Blood pressure reduction: GLP-1 RAs lower blood pressure, which is a key risk factor for LVH development and progression 3
• Weight loss: Significant weight reduction achieved with GLP-1 RAs may reduce cardiac workload and improve ventricular remodeling 4
• Anti-inflammatory effects: GLP-1 RAs reduce systemic inflammation, which may contribute to improved cardiac structure 3

Evidence-Based Recommendations

For Patients with Type 2 Diabetes and LVH:

• GLP-1 receptor agonists with proven cardiovascular benefit are strongly recommended (Class I, Level A) to reduce cardiovascular events, independent of baseline HbA1c 1
• Preferred agents include:
  • Liraglutide (13% relative risk reduction in MACE)
  • Semaglutide (26% relative risk reduction in MACE)
  • Dulaglutide (12% relative risk reduction in MACE) 5

For Non-Diabetic Patients with LVH:

• Semaglutide should be considered (Class IIa, Level B) in overweight (BMI >27 kg/m²) or obese patients to reduce cardiovascular mortality, MI, or stroke 1
• The cardiovascular benefits appear to extend beyond glycemic control, suggesting potential benefit in non-diabetic patients with LVH 3

Important Considerations and Cautions

Heart Failure Screening

• Critical safety consideration: Before initiating GLP-1 RAs in patients with LVH, perform comprehensive heart failure screening 2:
  • Directed clinical history and physical examination
  • Echocardiogram to assess ejection fraction
  • Measurement of natriuretic peptides (BNP or NT-proBNP)

Ejection Fraction-Based Approach

• HFpEF (preserved ejection fraction): GLP-1 RAs may be used with caution; they don't reduce HF hospitalizations but may reduce atherosclerotic events 2
• HFrEF (reduced ejection fraction): Use with significant caution due to potential risk of worsening heart failure events and arrhythmias 1, 2

Monitoring

• Regular assessment of:
  • Cardiac function via echocardiography
  • Renal function when initiating or escalating doses
  • Symptoms of heart failure decompensation 5

Practical Implementation

1. Initial dosing: Start with lower doses and titrate gradually to minimize gastrointestinal side effects 5

   • Semaglutide: Start 0.25 mg weekly, target 2.4 mg weekly
   • Liraglutide: Start 0.6 mg daily, target 3.0 mg daily

2. Nutritional support: Implement strategies to prevent muscle and bone loss during weight reduction 4

   • Adequate protein intake
   • Resistance training
   • Consider nutritional consultation

3. Monitoring for adverse effects:

   • Gastrointestinal symptoms (nausea, vomiting, diarrhea)
   • Potential thyroid issues (monitor for nodules, persistent hoarseness) 5

Conclusion

While GLP-1 RAs show promise for patients with moderate concentric LVH, particularly through epicardial fat reduction and cardiovascular risk modification, careful patient selection based on ejection fraction status is essential. The strongest evidence supports their use in patients with diabetes and established cardiovascular disease, but emerging evidence suggests benefits may extend to non-diabetic patients with LVH as well.