Congenital heart diseaseCohort study
Genetic Determinants of Early Heart Failure in Hypoplastic Left Heart Syndrome
- Prospective cohort study
- ambispective cohort
- external validation cohorts
- multicentre
- Genome sequencing in all participants
Authors' conclusion
This study provides the first prospective evidence linking dilated cardiomyopathy-associated variants to early-onset HF in HLHS.
Study context
- Population
- Neonates with hypoplastic left heart syndrome (HLHS), prospectively enrolled within the first 21 days of lifeprospective neonatal cohort
- Participants
- 35 neonates
- Exposure
- Likely pathogenic/pathogenic variant vs genotype-negative
- Outcome
- HF: severe (ventricular assist device, heart transplantation or death) or medically managed (reduced systemic ventricular EF and/or HF diagnosis requiring initiation or escalation of HF therapy)
Main finding
Severe HF
Increased risk
9-fold
P = 0.02
As reported in the abstract
Observational data: associations, not effects.
Further findings
| Outcome | fold increased risk | P value |
|---|---|---|
| Severe HF, external cohorts (Nationwide Children's Hospital; Vanderbilt University Medical Center) — Likely pathogenic/pathogenic variant vs Genotype-negative · Nationwide Children's Hospital cohort | 11 | P < 0.05 |
| Severe HF, external cohorts (Nationwide Children's Hospital; Vanderbilt University Medical Center) — Likely pathogenic/pathogenic variant vs Genotype-negative · Vanderbilt University Medical Center cohort | 3 | P < 0.05 |
Heart failure (HF) status in the prospective neonatal cohort
- Severe HF
- 7 (20.0%)
- Medically managed HF
- 10 (28.6%)
- HF free
- 18 (51.4%)
- 35 neonates
Timing of severe HF events · first month of life
- Most severe HF events occurred within the first month of life
- 67%
Severe HF, ambispective cohort
- Associations attenuated in the ambispective cohort
- all P > 0.05
- Ambispective cohort significantly older than the prospective cohort
- P < 0.0001
Original publication
Genetic Determinants of Early Heart Failure in Hypoplastic Left Heart Syndrome. J Am Coll Cardiol. Published 8 September 2026. doi:10.1016/j.jacc.2026.06.031
Summarised from the published abstract; every number is checked against it