Biomarker Phenotypes in Heart Failure with Preserved Ejection Fraction Using Hierarchical Clustering: A Pilot Study

Area of Science:

• Cardiology
• Biomarker Discovery
• Heart Failure Research

Background:

• Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous condition.
• Identifying distinct patient subgroups is crucial for understanding HFpEF pathophysiology.
• Biomarker profiling can aid in stratifying HFpEF patients.

Purpose of the Study:

• To identify and characterize distinct phenotype-based groups within the HFpEF population using unsupervised hierarchical clustering of plasma biomarkers.
• To define these groups as "biomarker phenotypes" and compare their overall clinical characteristics, cardiac structure, and function.

Main Methods:

• A cross-sectional study involving 75 HFpEF patients.
• Agglomerative hierarchical clustering was performed using plasma concentrations of cardiac remodeling biomarkers, B-type natriuretic peptide (BNP), and cystatin C.

Main Results:

• Two distinct biomarker phenotypes were identified: "remodeled" and "non-remodeled".
• The "remodeled phenotype" exhibited higher cardiac remodeling biomarkers, cystatin C, myocardial infarction, STEMI, atrial fibrillation, and anemia.
• This phenotype also showed increased left ventricular remodeling parameters and prolonged intermediate pauses on echocardiography.

Conclusions:

• Unsupervised hierarchical clustering effectively identifies two distinct biomarker phenotypes in HFpEF patients.
• These phenotypes differ significantly in clinical presentation, cardiac structure, and function.
• The findings suggest distinct pathophysiological mechanisms within the HFpEF cohort, with one phenotype aligning with reduced ejection fraction characteristics.