What is the role of milrinone (phosphodiesterase inhibitor) in patients with Heart Failure with preserved Ejection Fraction (HFpEF) and pulmonary hypertension?

From the Guidelines

Milrinone should be used cautiously as a short-term therapy in specific clinical scenarios for patients with Heart Failure with preserved Ejection Fraction (HFpEF) and pulmonary hypertension, particularly when right ventricular dysfunction is present due to pulmonary hypertension. When considering the use of milrinone in HFpEF patients with pulmonary hypertension, it is essential to weigh the potential benefits against the risks. The primary goal of using milrinone in this context is to provide temporary inotropic support and improve right ventricular function, thereby reducing pulmonary pressures.

• Key considerations for milrinone use in HFpEF patients with pulmonary hypertension include:
  • Acute decompensation with evidence of low cardiac output
  • Presence of right ventricular dysfunction due to pulmonary hypertension
  • Need for careful monitoring of hemodynamic response, renal function, electrolytes, and potential for hypotension
• Typical dosing involves an optional loading dose of 50 μg/kg over 10 minutes, followed by continuous infusion at 0.1-0.75 μg/kg/minute, titrated based on hemodynamic response, as seen in critically ill patients with pulmonary arterial hypertension 1. Milrinone works by inhibiting phosphodiesterase-3, which increases intracellular cyclic AMP, enhancing cardiac contractility and causing vasodilation in both pulmonary and systemic circulation. This dual action can improve right ventricular function and reduce pulmonary pressures, as noted in the management of critically ill PAH patients 1. However, milrinone should not be used long-term in HFpEF as it may increase mortality risk and requires careful monitoring of renal function, electrolytes, and hemodynamic parameters. Alternative or complementary approaches focusing on treating underlying causes of pulmonary hypertension and managing volume status are generally preferred for long-term management of these patients.

From the Research

Milrinone Challenge in Pulmonary Hypertension and HFpEF

• The role of milrinone, a phosphodiesterase inhibitor, in patients with Heart Failure with preserved Ejection Fraction (HFpEF) and pulmonary hypertension is not directly addressed in the provided studies 2, 3, 4, 5, 6.
• However, the studies discuss the pathophysiology, diagnosis, and treatment of pulmonary hypertension in HFpEF, highlighting the challenges and limitations of current therapeutic options 2, 3, 4.
• Phosphodiesterase inhibitors, such as milrinone, are mentioned as potential therapeutic agents for targeting the pulmonary vasculature in PH-HFpEF, but the evidence is limited and inconsistent 4, 5, 6.
• The mainstay of therapy for PH-HFpEF remains the treatment of the underlying HFpEF condition, with emerging evidence suggesting that newer HF therapies may improve hemodynamics and quality of life in these patients 4.

Diagnostic and Therapeutic Challenges

• The diagnosis of PH in HFpEF can be challenging, requiring a comprehensive and systematic approach using history, clinical examination, and noninvasive and invasive evaluation 3.
• The distinction between isolated postcapillary pulmonary hypertension (IpcPH) and combined postcapillary and precapillary pulmonary hypertension (CpcPH) is crucial, as therapeutic pathways differ between the two conditions 3.
• Therapeutic options for PH-HFpEF are limited, and more research is needed to develop effective medical therapies for this challenging population 2, 4.