Clinical Phenotypes of Heart Failure across the spectrum of Ejection Fraction: A Cluster Analysis

Curr Probl Cardiol. 2022 Nov;47(11):101337. doi: 10.1016/j.cpcardiol.2022.101337. Epub 2022 Jul 22.

Abstract

Introduction: Heart failure (HF), and especially HF with preserved ejection fraction (HFpEF), remains a challenging condition to define. The heterogenous nature of this population may be related to a variety of underlying etiologies interacting myocardial dysfunction.

Method: Alberta HEART study was a prospective, observational cohort that enrolled participants along the spectrum of heart failure including: healthy controls, people at risk of HF, and patients with HF and preserved (HFpEF) or reduced ejection fraction (HFrEF). We aimed to explore phenotypes of patients with HF and at-risk of developing HF. Utilising 27 detailed clinical, echocardiographic and biomarker variables, latent class analysis with and without multiple imputation was undertaken to identify distinct clinical phenotypes.

Results: Of 621 participants, 191 (30.8%) and 169 (27.2%) were adjudicated by cardiologists to have HFpEF and HFrEF respectively. In the overall cohort, latent class analysis identified four distinct phenotypes. Phenotype A (n=152, 24.5%) was a healthy and low risk group. Phenotype B (n=129, 20.8%) demonstrated increased left ventricular mass and end-diastolic volumes, with elevated natriuretic peptides and clinical features of congestion. Phenotype C (n=128, 20.6%) was primarily characterised by obesity (80%) and normal indexed cardiac chamber sizes, low natriuretic peptide levels and minimal features of congestion. Phenotype D (n=212, 34.1%) consisted of elderly patients with clinical features of congestions. Phenotypes B and D demonstrated the highest risk of mortality and hospitalization over a median follow-up of 3.7 years.

Conclusion: Phenotypes with congestive features demonstrated increased risk profiles. Heart failure is a heterogenous classification which requires further work to appropriately categorise patients based on the underlying etiology or mechanism of impairment.

MeSH terms

  • Biomarkers
  • Cluster Analysis
  • Heart Failure* / diagnosis
  • Heart Failure* / epidemiology
  • Heart Failure* / etiology
  • Humans
  • Natriuretic Peptides
  • Phenotype
  • Prognosis
  • Prospective Studies
  • Stroke Volume
  • Ventricular Function, Left

Substances

  • Biomarkers
  • Natriuretic Peptides