Phenotypes Identified for Heart Failure With Different Ejection Fraction Types

Human heart attack, computer illustration.
Researchers sought to determine unique phenotypes for patients with heart failure or that may be at risk for developing heart failure.

Patients with heart failure with preserved ejection fraction (HFpEF) or HF with reduced ejection fraction (HFrEF) have multiple unique phenotypes, and those with congestive features have increased risk profiles, according to a study in Current Problems in Cardiology.

The prospective, observational Alberta Heart Failure Etiology and Analysis Team study recruited patients with HF or with a risk for HF from Alberta, Canada, between 2010 and 2014. Investigators evaluated cardiovascular (CV) phenotypes across a spectrum of EF.

A total of 32 candidate variables were considered in the analysis. Clinical outcomes included all‐cause mortality, a composite of all‐cause mortality or hospitalization, a composite of all‐cause mortality or hospitalization for CV causes, and hospitalization for CV causes.

A total of 621 participants were included, 18.5% participants were classified into group 1 (risk of HFpEF), 7.7% were in group 2 (risk of HFpEF with CV comorbidities), 30.8% were in group 3 (known HFpEF), 27.2% were in group 4 (known HFrEF), and 15.9% of patients were in group 5 (healthy control individuals).

After a median follow‐up of 3.7 years (IQR, 2.4-4.8 years), 64 deaths, 308 hospitalizations for all causes, and 72 hospitalizations for CV causes occurred. Latent class analyses indicated 4 classes of phenotypes, and all participants were assigned to the class with the highest posterior probability.

Phenotype A (healthy) includes 152 participants (median age, 62 years; 46% men), most of whom are healthy (55%) with a risk of HF without CV comorbidities (32%). Phenotype B (dilated, hypertrophic left ventricle), includes 129 participants (median age, 65 years; 84% men) and is characterized by the highest indexed left ventricular end-diastolic volumes and left ventricular mass, as well as elevated natriuretic peptides and hs-troponin levels.

Phenotype C (obesity) includes 128 participants (median age, 61 years; 59% men) and is characterized primarily by the high prevalence of obesity (80%). This group is without cardiac chamber enlargement and had minimal other comorbidities. Phenotype D (congested and elderly) includes 212 participants (median age, 76 years; 46% men) and has features of congestion, including high natriuretic peptide levels, elevated jugular venous pressure (40%), and New York Heart Association class 2 or higher shortness of breath (67%).

Phenotype B is associated with an increased risk for clinical outcomes compared with phenotype A, including all-cause mortality (hazard ratio [HR], 13.5; 95% CI 3.2-56.8), composite of all-cause mortality or any hospitalization (HR, 4.0; 95% CI 2.7-5.9), composite of all-cause mortality and CV hospitalization (HR, 3.27; 95% CI 2.2-4.9), and CV hospitalization (HR, 11.5; 95% CI 4.5-29.0). Phenotype D has a comparable high risk of clinical outcomes, and phenotype C has a lower risk of adverse outcomes.

The researchers noted that their analysis may have limitations, including being complemented by the inclusion of emerging imaging biomarkers, such as left ventricular strain, direct imaging of cardiogenic pulmonary edema novel biomarker data, and serial imaging. Also, the presence of atrial fibrillation, diabetes, hypertension, and obesity is a requirement for inclusion and may have led to confounding during the latent class analyses. Furthermore, hospital in-patients are not included, and separation into smaller groups of about 100 individuals may limit the discriminative power of the analysis.

“Patients with HFpEF are a heterogenous population that demonstrate multiple unique phenotypes,” the study authors wrote. “As novel biomarkers and predictors of HF emerge, our ability to identify novel phenotypes will continue to improve.”


Gouda P, Alemayehu W, Rathwell S, et al. Clinical phenotypes of heart failure across the spectrum of ejection fraction: a cluster analysis. Curr Probl Cardiol. Published online July 22, 2022. doi: 10.1016/j.cpcardiol.2022.101337