Clinical Benefits of Medical Therapy in Adults With Congenital Heart Disease and Systemic Left Ventricular Presenting With Heart Failure With Reduced Ejection Fraction

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Congenital heart disease with heart failure and reduced ejection fraction (n=778). Intervention: Guideline-directed medical therapy (GDMT) vs. Lower GDMT score / No uptitration. Primary outcome: Heart failure hospitalization (HR 0.81, 95% CI 0.74-0.88, p=<0.001).

Q: What does this research mean for the field?

In adults with congenital heart disease and heart failure with reduced ejection fraction, higher baseline guideline-directed medical therapy use and uptitration over time are associated with a reduced risk of heart failure hospitalization and mortality. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Mohamed Ellabbad; Zeyad Kholeif; Shannon M. Dunlay; Maan Jokhadar; David Majdalany; Alexander C. Egbe

doi:10.1161/jaha.125.048260

May 25, 2026Journal of the American Heart AssociationOpen Access

Clinical Benefits of Medical Therapy in Adults With Congenital Heart Disease and Systemic Left Ventricular Presenting With Heart Failure With Reduced Ejection Fraction

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Key result

Higher baseline guideline-directed medical therapy score (HR 0.81 per 1-point increase) and uptitration over time (HR 0.70) were associated with a lower risk of heart failure hospitalization.

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Why the study?

The study was conducted to assess the clinical benefits of guideline-directed medical therapy for heart failure in adults with congenital heart disease and heart failure with reduced ejection fraction.

Does higher guideline-directed medical therapy (GDMT) use and uptitration reduce heart failure hospitalization and mortality in adults with congenital heart disease and systemic left ventricular ejection fraction <50%?

Study Design

Type

Cohort (n=778)

Multicenter

No

Structured PICO

Does higher guideline-directed medical therapy (GDMT) use and uptitration reduce heart failure hospitalization and mortality in adults with congenital heart disease and systemic left ventricular ejection fraction <50%?

P

Population

778 adults (≥18 years) with congenital heart disease and systemic left ventricular ejection fraction <50%, followed for a median of 5.3 years.

E

Exposure

Higher guideline-directed medical therapy (GDMT) score at baseline and GDMT uptitration (increase in GDMT score over 1 year). Medications included beta-blockers, ACEI/ARB/ARNI, MRA, and SGLT2i.

C

Comparator

Lower baseline GDMT score and no GDMT uptitration (change in GDMT score ≤0 over 1 year).

O

Outcome

Heart failure hospitalization (defined as hospital admission for volume overload requiring intravenous diuretics) from 1-year follow-up.hard clinical

Main Result

Hazard Ratio: 0.81 (95% CI 0.74–0.88)

p-value: p=<0.001

In adults with congenital heart disease and systemic left ventricular ejection fraction <50%, higher baseline use and subsequent uptitration of guideline-directed medical therapy are associated with significantly lower risks of heart failure hospitalization and mortality.

Limitations

Retrospective single center study prone to selection and ascertainment bias
Included patients with different CHD diagnoses increasing population heterogeneity
Unable to ascertain adherence with prescribed medications
Risk of model over-fitting due to the number of covariates included in the model
Did not adjust for temporal changes in GDMT after the first year of follow-up
Primary analysis created a selection bias by excluding patients who died or were lost to follow-up prior to the 1-year encounter
Underestimation of the incidence of HF hospitalization for patients hospitalized within 1 year from the baseline encounter
Retrospective chart review design

Implication

Supports GDMT optimization in congenital HFrEF; leaves open causal benefit pending randomized trials.

Abstract

Background The purpose of this study was to assess the clinical benefits of guideline‐directed medical therapy (GDMT) for heart failure (HF) in adults with congenital heart disease and HF with reduced ejection fraction. Methods HF with reduced ejection fraction was defined as stage B/C HF and systemic left ventricular ejection fraction <50%. GDMT score was assessed at baseline encounter (baseline GDMT score) and 1‐year follow‐up. GDMT uptitration was calculated as defined as ∆GDMT score from baseline. Cox regression was used to assess the relationship between HF therapy (baseline and ∆GDMT score) and outcomes (HF hospitalization and mortality). Results Of 778 patients (age 44±16, 480 [62%] males), baseline GDMT score was 2 (1, 3) and ∆GDMT score was 0.62 (95% CI, 0.55–0.69). Of 778, only 258 (33%) had GDMT uptitration (∆GDMT score >0). Higher use of GDMT at baseline (adjusted HR per 1 point increase in GDMT score 0.81, 95% CI, 0.74–0.88, P <0.001), and increased use of GDMT over time (adjusted HR for 1 point increase in ∆GDMT score HR 0.70, 95% CI, 0.61–0.79, P <0.001) were associated with lower risk of HF hospitalization. Higher baseline GDMT score (adjusted HR 0.85, 95% CI, 0.76–0.94, P <0.001), and ∆ GDMT score (adjusted HR 0.82, 95% CI, 0.71–0.94, P <0.000) were also associated with lower mortality. Conclusions GDMT use at baseline and GDMT uptitration were associated with improved outcomes and suggest a dose‐dependent relationship between use of GDMT and risk of adverse outcomes. Furthermore, 67% of patients did not receive GDMT uptitration, suggesting suboptimal therapy, and opportunities for improvement.

Discussion

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Cite This Study

Ellabbad et al. (2026) conducted a cohort in Congenital heart disease with heart failure and reduced ejection fraction (n=778). Guideline-directed medical therapy (GDMT) vs. Lower GDMT score / No uptitration was evaluated on Heart failure hospitalization (HR 0.81, 95% CI 0.74-0.88, p=<0.001). Higher baseline guideline-directed medical therapy score (HR 0.81 per 1-point increase) and uptitration over time (HR 0.70) were associated with a lower risk of heart failure hospitalization.

synapsesocial.com/papers/6a162b04533f3b97d8c503ed https://doi.org/10.1161/jaha.125.048260