Effect of Empagliflozin on Neutrophil and Lymphocyte Counts, and their Ratio, in Patients with Heart Failure: the EMPEROR Program

Heart failure is a condition characterized by fluid buildup (congestion) and inflammation. It affects millions of people worldwide and can lead to symptoms such as shortness of breath and adverse health outcomes. There are two main types of heart failure:

• Heart failure with reduced ejection fraction (HFrEF): the heart’s ability to pump blood is weakened.
• Heart failure with preserved ejection fraction (HFpEF): the heart’s pumping ability is preserved, but its function is still impaired.

Sodium-glucose co-transporter-2 (SGLT2) inhibitors, such as empagliflozin, were originally developed to treat type 2 diabetes by promoting the excretion of excess glucose in urine. However, they have also been shown to reduce congestion and systemic inflammation in patients with heart failure, and to improve outcomes in this population.

The neutrophil-to-lymphocyte ratio (NLR) reflects the balance between two types of white blood cells:
• Neutrophils, which increase in response to inflammation.
• Lymphocytes, which may decrease in heart failure, particularly when congestion is severe.

A higher NLR may therefore indicate a combination of inflammation and fluid overload. Previous research has shown that patients with heart failure and a high NLR are more likely to experience poorer outcomes, especially those with HFrEF. Data are more limited in HFpEF.

Therefore, we propose to analyze two trials that evaluated the effects of SGLT2 inhibitors in patients with HFrEF and HFpEF to explore whether this treatment influences NLR or its individual components (neutrophil and lymphocyte counts). We will examine how white blood cell profiles relate to cardiac function and clinical outcomes, and whether these profiles change after initiating SGLT2 inhibitor therapy.

Through this research, we aim to enhance understanding of how inflammation and fluid retention contribute to heart failure, and how SGLT2 inhibitors may help target these underlying mechanisms.