Abstract
Heart failure with preserved ejection fraction (HFpEF) is a growing health problem worldwide, accounting for half of all heart failure cases. HFpEF patients present with diverse underlying causes and symptoms, making diagnosis and treatment challenging. Current pharmacological therapies are inadequate, while approved device-based therapies have shown limited success due to patient heterogeneity. This underscores the need for improved pre-clinical models, critical for guiding the design and development of effective therapeutic devices. This paper presents an overview of current pre-clinical HFpEF models, including in-silico, in-vitro, ex-vivo, and in-vivo approaches, aimed at advancing the understanding of HFpEF physiology and the development of device-based therapies. We examined each model's ability to replicate key HFpEF characteristics, discuss their respective strengths and limitations, and highlight their role in supporting the creation of clinically relevant solutions. Additionally, the potential of emerging advancements is explored.