Table.
Summary of Studies Using Proteomics and Machine Learning-Based Approaches for Endotype Derivation
| Author (year) | HF phenotype | Population (sample size) | Machine learning method used | Endotypes identified | Dysregulated pathways/protein biomarkers |
|---|---|---|---|---|---|
| Woolley et al (2021)20 | HFpEF | BIOSTAT-CHF (n=429) | Hierarchical clustering | Endotype 1: Younger, lower NT-proBNP Endotype 2: Older, CKD* Endotype 3: Multiple comorbidities Endotype 4: ICM |
Endotype 2: upregulation of inflammatory pathways Endotype 4: upregulation of cell proliferation regulation and cell survival pathways |
| Stienen et al (2020)21 | HFpEF | MEDIA-DHF (n=392) | k-means clustering | Endotype 1: Younger, fewer comorbidities Endotype 2: Multiple comorbidities including CKD* |
Endotype 2: upregulation of pathways involved in immune system activation, signal transduction cascades, and cell interactions and metabolism |
| Tromp et al (2018)22 | HFrEF | BIOSTAT-CHF (n=1,802) | Principal component analysis and partitioning around medoids | Endotype 1: Younger, lower NT-proBNP Endotype 2: Elderly, poor response to β-blocker uptitration, kidney disease Endotype 3: ICM Endotype 4: Highest NT-pro BNP, AF* Endotype 5: High rates of anemia Endotype 6: Hypertensive |
Endotype 4: Very high levels of IGFBP1 and NT-pro-BNP Endotype 5: Very low levels of CHIT1 (increased levels associated with arteriosclerosis and Gaucher’s disease) |
| Verdonschot et al (2021)51 | DCM | Maastricht Cardiomyopathy Registry (n=795) | Hierarchical clustering of principal components | Endotype 1: Younger patients with mild systolic dysfunction Endotype 2: Young females with auto-immune disease Endotype 3: Males with AF, NSVT, genotype positive* Endotype 4: Severe systolic dysfunction and diastolic dysfunction |
Endotype 2: Pro-inflammatory pathways Endotype 4: Increased glycolytic substrate usage, increased purine and pyrimidine metabolism reflecting increased DNA replication pathways |
Endotype associated with worse outcomes. AF, atrial fibrillation; BISOTAT-CHF, A Systems Biology Study to Tailored Treatment in Chronic Heart Failure; CKD, chronic kidney disease; DCM, dilated cardiomyopathy; HF, heart failure; HFmrEF, heart failure with mid-range ejection fraction; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; ICM, ischemic cardiomyopathy; IMMACULATE, Improving Remodeling in Acute Myocardial Infarction Using Live and Asynchronous Telemedicine; LVDD, left ventricular diastolic dysfunction; MEDIA-DHF, The Metabolic Road to Diastolic Heart Failure: Diastolic Heart Failure study; MI, myocardial infarction; NSVT, non-sustained ventricular tachycardia; NT-proBNP, N-terminal-proB-type natriuretic peptide.