Figure 1: A stepwise phenotype-based approach to developing HFpEF models.

HFpEF is a clinical syndrome with complex systemic pathophysiology that includes functional impairments in both cardiac and extra-cardiac tissues. Developing reliable animal models of HFpEF requires that investigators rigorously assess and validate multiple clinically relevant phenotypes, starting with the hallmark features of HF, congestion and exercise intolerance (1^st panel). Next, preserved left ventricular ejection fraction, a defining feature of HFpEF, should be confirmed (2^nd panel). Additional cardiac and extra-cardiac phenotyping should then be assessed, and tailored to the specific phenogroup, being modeled (3^rd and 4^th panels). The illustration was made using images from smart.servier.com. Illustration credit: Ben Smith