Metabolomic Profile in HFpEF vs HFrEF Patients.

Area of Science:

• Cardiology
• Metabolomics
• Biochemistry

Background:

• Heart failure with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF) are linked to metabolic abnormalities with potentially differing impacts.
• Understanding these metabolic differences is crucial for targeted therapies.

Purpose of the Study:

• To compare the plasma metabolomic profiles of patients with new-onset HFpEF and HFrEF.
• To identify specific metabolites associated with HFpEF and HFrEF and their relation to clinical characteristics and comorbidities.

Main Methods:

• Targeted metabolomics was used to assess 109 endogenous plasma metabolites in 46 new-onset HFpEF patients (EF ≥50%) and 75 new-onset HFrEF patients (EF <40%).
• Statistical analyses explored differential metabolite levels and associations with clinical factors like age, sex, hypertension, diabetes, and kidney function.

Main Results:

• HFpEF patients were older, more often female, and had higher rates of hypertension, atrial fibrillation, and diabetes than HFrEF patients.
• HFpEF was associated with elevated hydroxyproline, symmetric dimethyl arginine, alanine, cystine, and kynurenine, indicating fibrosis, inflammation, and oxidative stress.
• Conversely, HFpEF patients had lower levels of serine, cGMP, cAMP, l-carnitine, lysophosphatidylcholine (18:2), lactate, and arginine compared to HFrEF patients.

Conclusions:

• New-onset HFpEF exhibits a distinct metabolic signature compared to HFrEF, closely tied to comorbidities like diabetes and kidney dysfunction.
• HFpEF is characterized by increased inflammation, oxidative stress, impaired lipid metabolism, heightened collagen synthesis, and reduced nitric oxide signaling.
• These metabolic differences suggest predominant systemic microvascular endothelial dysfunction and inflammation with increased fibrosis in HFpEF relative to HFrEF.