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Heart Failure with Recovered Ejection Fraction in Patients with Vinculin Loss-of-function Variants

Laura Zahavich1,2,3, Rajadurai Akilen4, Kristen George3

  • 1Department of Genetic Counselling, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.

Journal of Cardiovascular Translational Research
|August 7, 2023
PubMed

Insights

Genetic variants in vinculin (VCL) may predict heart recovery in infants with dilated cardiomyopathy (DCM). Over 80% of infants with VCL loss-of-function variants showed improved heart function, suggesting a genetic basis for heart recovery.

Area of Science:

  • Genetics
  • Cardiology
  • Molecular Biology

Background:

  • Predicting myocardial recovery in heart failure (HF) remains challenging.
  • Dilated cardiomyopathy (DCM) is a significant cause of heart failure in infants.
  • The genetic underpinnings of HF recovery are not well understood.

Purpose of the Study:

  • To investigate the association between vinculin (VCL) variants and myocardial recovery in infants with DCM.
  • To identify potential genetic predictors for HF recovery in pediatric populations.

Main Methods:

  • Case series analysis of six infants diagnosed with DCM and identified VCL loss-of-function (LOF) variants.
  • Evaluation of left ventricular (LV) ejection fraction (EF) and LV end-diastolic diameter z-score at diagnosis and during follow-up.
  • Assessment of response to standard HF medications.

Main Results:

  • Six infants with DCM and VCL LOF variants were identified, presenting with severely reduced LV ejection fraction (median 24%).
  • Despite initial severe HF, 83% of patients demonstrated normalization of LV function by a median age of 2.7 years.
  • One patient experienced disease progression requiring heart transplantation.

Conclusions:

  • Loss-of-function variants in the VCL gene are associated with a unique phenotype of DCM in infants.
  • A significant proportion of these patients exhibit spontaneous recovery of left ventricular function, suggesting a genetic basis for heart failure with recovered ejection fraction.
  • These findings have important prognostic implications for genetic counseling and clinical management of VCL-associated DCM.

Keywords:
Dilated cardiomyopathyHFrEFHFrecEFHeart failureMyocardial recoveryVinculin

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