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Lumped-Parameter and Finite Element Modeling of Heart Failure with Preserved Ejection Fraction
09:20

Lumped-Parameter and Finite Element Modeling of Heart Failure with Preserved Ejection Fraction

Published on: February 13, 2021

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Genetic architecture of heart failure with preserved versus reduced ejection fraction

Jacob Joseph1,2,3, Chang Liu4, Qin Hui4,5

  • 1Massachusetts Veterans Epidemiology Research and Information Center, VA Boston Healthcare System, Boston, MA, USA. jacob.joseph@va.gov.

Nature Communications
|December 14, 2022
PubMed

Insights

Genetic differences in heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) suggest distinct pathobiology. HFpEF likely comprises multiple entities, necessitating consensus sub-phenotyping for genetic discovery.

Area of Science:

  • Cardiovascular Genetics
  • Genomic Medicine
  • Heart Failure Pathophysiology

Background:

  • Pharmacologic trials for heart failure with preserved ejection fraction (HFpEF) show limited success compared to those for heart failure with reduced ejection fraction (HFrEF).
  • The genetic basis underlying HFpEF and HFrEF disparities remains largely unexplored, hindering therapeutic development.
  • Understanding genetic differences may illuminate divergent clinical trial outcomes and underlying disease mechanisms.

Purpose of the Study:

  • To investigate the genetic architectures of HFpEF and HFrEF using a large, uniformly phenotyped cohort.
  • To identify distinct genetic association profiles between HFpEF and HFrEF.
  • To explore the implications of genetic findings for HFpEF pathobiology and clinical trial outcomes.

Main Methods:

  • Genome-wide association studies (GWAS) were performed on a single cohort stratified into HFpEF and HFrEF groups.
  • Detailed genetic analyses were conducted to compare the genetic architectures of the two heart failure subtypes.
  • Phenotypic data were uniformly collected and sub-classification was based on current clinical definitions.

Main Results:

  • Significant differences in genetic architecture and association profiles were observed between HFpEF and HFrEF.
  • HFrEF exhibited a robust genetic discovery with 13 identified loci.
  • HFpEF showed modest genetic discovery with only one identified locus, suggesting heterogeneity.

Conclusions:

  • The distinct genetic profiles of HFpEF and HFrEF indicate differing underlying pathobiological mechanisms.
  • The limited genetic findings for HFpEF suggest it is an amalgamation of several distinct pathobiological entities.
  • Developing consensus sub-phenotyping for HFpEF is crucial for advancing genetic research and understanding this prevalent condition.

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