Obese-Inflammatory Phenotypes in Heart Failure With Preserved Ejection Fraction

Area of Science:

• Cardiology
• Immunology
• Genetics

Background:

• Heart failure with preserved ejection fraction (HFpEF) is often linked to comorbidity-driven microvascular inflammation.
• Obesity, a proinflammatory state, is highly prevalent in HFpEF patients.
• The study investigates the existence of distinct obesity-inflammation phenotypes within HFpEF.

Purpose of the Study:

• To identify unique obesity-inflammation phenotypes in patients with HFpEF.
• To associate these phenotypes with clinical features, biomarkers of fibrosis, and functional performance.
• To explore the role of inflammation in HFpEF pathophysiology.

Main Methods:

• Unsupervised machine learning (hierarchical clustering) was applied to 301 HFpEF patients from clinical trials.
• Input variables included obesity status and 13 inflammatory biomarkers.
• Associations between identified clusters and HFpEF severity markers, fibrosis biomarkers (PIIINP, CITP, IGFBP7, GAL-3), and functional metrics were assessed.

Main Results:

• Three distinct phenotypes emerged: pan-inflammatory (64% obese), noninflammatory (55% obese), and obese high CRP (98% obese).
• The pan-inflammatory group exhibited higher comorbidity burden, more hospitalizations, elevated cardiac biomarkers and fibrosis markers, and reduced functional capacity.
• The noninflammatory group showed the most favorable outcomes, while the obese high CRP group had isolated CRP elevation and poorer function.

Conclusions:

• Distinct obesity-inflammation phenotypes exist in HFpEF, correlating with differences in comorbidity, disease severity, and fibrosis.
• These findings support microvascular inflammation as a key mechanism in a significant subset of HFpEF patients.
• The identified phenotypes offer potential targets for personalized treatment strategies in HFpEF.