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Updated: Jun 11, 2026

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Published on: August 8, 2022

Genotype Predicts Heart Failure Independent of LVEF, Peak VO2, and NT-proBNP Levels in Hypertrophic Cardiomyopathy

Athanasios Bakalakos1, Alexandros Protonotarios1, Menelaos Pavlou2

  • 1Institute of Cardiovascular Science, University College London, London, United Kingdom; Barts Heart Centre, St Bartholomew's Hospital, London, United Kingdom.

JACC. Heart Failure
|June 10, 2026
PubMed

Insights

Genetic status significantly impacts heart failure outcomes in hypertrophic cardiomyopathy (HCM). Gene-positive patients face higher risks, highlighting the need for combined genetic and clinical assessments for personalized care.

Area of Science:

  • Cardiology
  • Genetics
  • Biomarkers

Background:

  • Hypertrophic cardiomyopathy (HCM) is a genetic myocardial disorder leading to heart failure (HF).
  • Genetic variants, particularly in sarcomere protein genes, account for about 40% of HCM cases.
  • Understanding genotype-phenotype correlations is crucial for predicting HF progression.

Purpose of the Study:

  • To investigate the association between genetic status and clinical predictors of HF outcomes in HCM patients.
  • To identify key factors that independently predict adverse HF events in individuals with HCM.
  • To explore the combined predictive value of genotype, biomarkers, and functional capacity for HF outcomes.

Main Methods:

  • An observational, single-center cohort study of 505 genotyped HCM patients.
  • Stratification into gene-positive (G+) and gene-elusive (G-) groups.
  • Analysis using proportional hazards models for primary (HF-related death/transplant) and secondary endpoints, considering genetic status, NT-proBNP, peak VO2, and LVEF.

Main Results:

  • Gene-positive (G+) HCM patients had a significantly higher incidence of HF-related death or transplantation (12.8%) compared to gene-elusive (G-) patients (2.1%).
  • Independent predictors of HF outcomes included G+ status (HR: 5.86), elevated log NT-proBNP (HR: 2.46), reduced peak VO2 (HR: 0.90), and lower LVEF (HR: 0.74 per 5% increment).
  • Secondary endpoints revealed significant cardiac mortality (11.9%), arrhythmic events (6.7%), and all-cause mortality (22.8%) over a median follow-up of 10.6 years.

Conclusions:

  • Genetic status, peak VO2, log NT-proBNP, and LVEF are independent predictors of HF outcomes in HCM.
  • Integrating genetic information with clinical biomarkers and functional assessments can identify high-risk HCM patients.
  • This combined approach may guide targeted monitoring and patient selection for clinical trials investigating disease-modifying therapies.
Abstract

Keywords:
brain natriuretic peptidegenotypeheart failurehypertrophic cardiomyopathyprognosisrisk stratification

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