Heart failure (HF) is a complex syndrome characterized by multiple aetiologies and a progressive clinical course with a strong impact in terms of morbidity, mortality and public health costs.
According to the neurohormonal hypothesis, HF with reduced ejection fraction (HFrEF) is considered a neurohormonal disease and HF patients benefit from the use of medications that interfere with and modulate the negative effects of neurohormonal systems (i.e. permanent renin–angiotensin–aldosterone system activation). The foundation of HF treatment includes the combination of well-known neurohormonal antagonists such as angiotensin receptor neprilysin inhibitors, beta-blockers, and mineralocorticoid receptor antagonists. However, recently, Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2-i) have emerged as a new additional cornerstone of HF treatment – they are now regarded as one of the four keystone drugs to be introduced as first line therapy in HFrEF (class I recommended drug). Moreover, SGLT2-i have been shown to decrease combined endpoints of cardiovascular mortality and worsening HF regardless of ejection fraction (EF), and also to prevent the onset of HF in patients who are at high cardiovascular risk.
The pathophysiologic mechanisms that may explain the benefit in clinical outcomes of the SGLT2-i in patients with HF are still incompletely understood. Therefore, it is of great interest to analyze the biological changes, which may occur in patients taking SGLT2-i because this may be helpful to elucidate how SGLT2-i may lead to improved cardiovascular outcomes. In this context, the metanalysis published in the European Journal of Internal Medicine by Fan et al. is timely and relevant because it evaluates the potential structural and functional impact of SGLT2-i in human heart giving possible translational understandings of the biologic consequences caused by SGLT2-i.
