What is Cardiometabolic HFpEF and How Can We Study it Preclinically?

• Published in: JACC. Basic to translational science p. 101295
• Main Authors: Daou, Daniel, MD, Tong, Dan, MD, PhD, Schiattarella, Gabriele G., MD, PhD, Gillette, Thomas G., PhD, Hill, Joseph A., MD, PhD
• Format: Journal Article
• Language: English
• Published: United States 03.06.2025
• Subjects: Cardiovascular; db/db; eNOS; surgical aortic banding; ejection fraction; TTE; ob/ob; HFD; HFpEF; cardiometabolic; HFrEF; WD; GLS; inducible nitric oxide synthase; heart failure with preserved ejection fraction; endothelial nitric oxide synthase; iNOS; N ω-nitro-L-arginine methyl ester; heart failure with reduced ejection fraction; AB; EF; Maximal oxygen uptake; preclinical models; L-NAME; transthoracic echocardiography; leptin receptor-deficient mice; Ang II; global longitudinal strain; angiotensin II; high-fat diet; leptin-deficient mice; EAT; epicardial adipose tissue; VO 2max; Western diet
• ISSN: 2452-302X; 2452-302X
• DOI: 10.1016/j.jacbts.2025.04.009

Cardiometabolic heart failure with preserved ejection fraction (HFpEF) has emerged as a distinct and dominant endotype of HFpEF. Driven by prevalent comorbidities, its incidence and prevalence are projected to continue to rise amid the current global pandemic of obesity and metabolic disease. Recognizing the characteristic clinical and molecular features of cardiometabolic HFpEF is paramount for developing an efficacious therapeutic arsenal and improving clinical outcomes, challenges in which success to date has been modest. Studying relevant and clinically informative animal models of cardiometabolic HFpEF can afford valuable insights into the molecular underpinnings of this syndrome, allowing the possibility of novel advances with clinical relevance. Here, we outline the clinical and molecular features that define cardiometabolic HFpEF as a distinct endotype. We also discuss the bona fide animal models of cardiometabolic HFpEF currently available, as well as methods for developing new models.