Polygenic Score for β-Blocker Survival Benefit in European Ancestry Patients With Reduced Ejection Fraction Heart Failure

David E. Lanfear*, Jasmine A. Luzum, Ruicong She, Hongsheng Gui, Mark P. Donahue, Christopher M. O'Connor, Kirkwood F. Adams, Sandra Sanders-van Wijk, Nicole Zeld, Micha T. Maeder, Hani N. Sabbah, William E. Kraus, Hans-Peter Brunner-La Rocca, Jia Li, L. Keoki Williams

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Web of Science)

Abstract

Background:

beta-Blockers (BBs) are mainstay therapy for heart failure with reduced ejection fraction. However, individual patient responses to BB vary, which may be partially due to genetic variation. The goal of this study was to derive and validate the first polygenic response predictor (PRP) for BB survival benefit in heart failure with reduced ejection fraction patients.

Methods:

Derivation and validation analyses were performed in n=1436 total HF patients of European descent and with ejection fraction

Results:

Five-fold cross-validation summaries out to 1000 single-nucleotide polymorphisms identified optimal prediction with a 44 single-nucleotide polymorphism score and cutoff at the 30th percentile. In validation testing (n=1188), greater BB exposure was associated with reduced all-cause mortality in patients with low PRP score (n=251; hazard ratio, 0.19 [95% CI, 0.04-0.51]; P=0.0075) but not high PRP score (n=937; hazard ratio, 0.84 [95% CI, 0.53-1.3]; P=0.448)-a difference that was statistically significant (P interaction, 0.0235). Results were consistent regardless of atrial fibrillation, ejection fraction (

Conclusions:

Among patients of European ancestry with heart failure with reduced ejection fraction, a PRP distinguished patients who derived substantial survival benefit from BB exposure from a larger group that did not. Additional work is needed to prospectively test clinical utility and to develop PRPs for other population groups and other medications.

Original languageEnglish
Article number007012
Number of pages12
JournalCirculation-Heart Failure
Volume13
Issue number12
DOIs
Publication statusPublished - Dec 2020

Keywords

  • atrial fibrillation
  • pharmacogenetics
  • population groups
  • precision medicine
  • 2013 ACCF/AHA GUIDELINE
  • ASSOCIATION TASK-FORCE
  • RISK SCORE
  • ADRENERGIC-RECEPTOR
  • ATRIAL-FIBRILLATION
  • AMERICAN-COLLEGE
  • PROPENSITY SCORE
  • GENETIC RISK
  • VARIANTS
  • COMMON

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