Objective:

To reframe heart failure with preserved ejection fraction (HFpEF) as a systemic disease influenced by inflammatory and metabolic factors, highlighting its complexity beyond a myocardial disorder.

Key Findings:

• HFpEF is increasingly recognized as a systemic inflammatory and metabolic condition, influenced by factors such as obesity and diabetes.
• Conventional cardiac-centered models fail to explain the disease's association with obesity, diabetes, and systemic inflammation.
• The liver and pancreas play significant roles in the pathophysiology of HFpEF, contributing to cardiac dysfunction through systemic mechanisms.
• Therapies targeting systemic inflammation and metabolic health may improve outcomes in HFpEF patients, as evidenced by recent clinical findings.

Interpretation:

HFpEF should be viewed as a complex interplay of systemic factors rather than a primary cardiac disorder, necessitating a multidisciplinary approach to treatment that includes addressing metabolic and inflammatory contributors.

Limitations:

• The article may not address all potential systemic contributors to HFpEF, such as renal dysfunction or other endocrine factors.
• Further research is needed to validate the proposed cardio-hepato-pancreatic model and its implications for treatment.

Conclusion:

Recognizing HFpEF as a systemic disorder opens avenues for novel therapeutic strategies that target inflammation and metabolic dysfunction across multiple organ systems.