What is the role of bromocriptine in peripartum cardiomyopathy?

Role of Bromocriptine in Peripartum Cardiomyopathy

Bromocriptine should be added to standard heart failure therapy in women with peripartum cardiomyopathy (PPCM) as it significantly improves left ventricular function recovery and clinical outcomes. 1

Pathophysiological Basis

Bromocriptine's effectiveness in PPCM is based on a specific pathophysiological mechanism:

• PPCM involves an oxidative stress-cathepsin D-16 kDa prolactin cascade 2
• Oxidative stress activates cathepsin D in cardiomyocytes, which cleaves prolactin into a 16 kDa angiostatic and pro-apoptotic fragment 2
• This 16 kDa prolactin fragment:
  • Inhibits endothelial cell proliferation and migration
  • Induces endothelial cell apoptosis
  • Disrupts capillary structures
  • Promotes vasoconstriction
  • Impairs cardiomyocyte function 2
• Bromocriptine, a dopamine D2 receptor agonist, suppresses prolactin production, thereby interrupting this pathological cascade 2, 1

Evidence for Efficacy

The evidence supporting bromocriptine use in PPCM is substantial:

• A pilot study showed significantly greater recovery of left ventricular ejection fraction (LVEF) in patients receiving bromocriptine plus standard care (27% to 58%) compared to standard care alone (27% to 36%) 3
• The BRO-HF retrospective cohort study demonstrated that bromocriptine was independently associated with greater LV functional recovery, with a 14.1% greater improvement in LVEF after adjusting for clinical variables 4
• A 2025 meta-analysis of 11 studies involving 1,706 participants found bromocriptine was associated with:
  • Greater LVEF improvement (mean difference 10.03%, 95% CI 3.88% to 16.17%)
  • Higher post-treatment LVEF (mean difference 8.50%, 95% CI 3.39% to 13.61%) 5
• Bromocriptine has shown benefit even in cases with predominant LV diastolic dysfunction 6 and in fulminant PPCM requiring mechanical circulatory support 7

Treatment Protocol

The recommended bromocriptine regimen is:

• 2.5 mg twice daily for 2 weeks, followed by
• 2.5 mg daily for 4 weeks 1
• Consider longer protocol for patients with severe PPCM 1

Important Safety Considerations

When using bromocriptine in PPCM:

1. Mandatory anticoagulation is essential for all PPCM patients with low LVEF receiving bromocriptine to prevent thromboembolic complications 1
2. Monitor for potential side effects including:
   • Orthostatic hypotension
   • Mood changes 1
3. Earlier initiation of therapy is associated with better outcomes 1

Integration with Standard Heart Failure Therapy

Bromocriptine should be used as an adjunct to standard heart failure therapy, which includes:

• Beta-blockers
• ACE inhibitors/ARBs (postpartum only, as they are contraindicated during pregnancy)
• Diuretics (if needed for congestion)
• Hydralazine/nitrates (particularly during pregnancy) 2

Timing Considerations

• Initiate bromocriptine as early as possible after diagnosis 1
• For antepartum PPCM, bromocriptine should be considered immediately postpartum 2
• Avoid premature device therapy (ICD implantation) given the high rates of improvement with bromocriptine and standard heart failure therapy 1

Key Pitfalls to Avoid

1. Failure to provide anticoagulation when using bromocriptine - this is mandatory to prevent thromboembolism
2. Delaying bromocriptine initiation - earlier treatment is associated with better outcomes
3. Using bromocriptine as a replacement for (rather than addition to) standard heart failure therapy
4. Premature device therapy before allowing adequate time for recovery with medical therapy

Bromocriptine represents a targeted therapy addressing a specific pathophysiological mechanism in PPCM, and its addition to standard heart failure therapy should be considered in all patients with newly diagnosed PPCM.