Clinical Benefits of Medical Therapy in Adults With Congenital Heart Disease and Systemic Left Ventricular Presenting With Heart Failure With Reduced Ejection Fraction.
Ellabbad M, Kholeif Z, et al. • Journal of the American Heart Association • 2026
Higher use of guideline-directed medical therapy at baseline and increased use over time were associated with lower risk of heart failure hospitalization and mortality in adults with congenital heart disease and heart failure with reduced ejection fraction, with a dose-dependent relationship observed.
Key Findings
Results
Higher baseline GDMT use was associated with significantly lower risk of heart failure hospitalization in adults with congenital heart disease and HFrEF.
Adjusted HR per 1 point increase in baseline GDMT score was 0.81 (95% CI, 0.74–0.88, P<0.001)
GDMT score was assessed at baseline encounter and 1-year follow-up
Study population included 778 patients (age 44±16, 480 [62%] males)
Heart failure with reduced ejection fraction was defined as stage B/C HF and systemic left ventricular ejection fraction <50%
Results
GDMT uptitration over time was associated with a lower risk of heart failure hospitalization.
Adjusted HR for 1 point increase in ΔGDMT score was 0.70 (95% CI, 0.61–0.79, P<0.001)
GDMT uptitration was defined as ΔGDMT score from baseline to 1-year follow-up
The mean ΔGDMT score was 0.62 (95% CI, 0.55–0.69)
Only 258 of 778 patients (33%) had GDMT uptitration (ΔGDMT score >0)
Results
Higher baseline GDMT score was associated with significantly lower mortality.
Adjusted HR for mortality per 1 point increase in baseline GDMT score was 0.85 (95% CI, 0.76–0.94, P<0.001)
Cox regression was used to assess the relationship between HF therapy and outcomes
Both HF hospitalization and mortality were examined as outcomes
Results
GDMT uptitration over time was also associated with lower mortality.
Adjusted HR for mortality per 1 point increase in ΔGDMT score was 0.82 (95% CI, 0.71–0.94, P<0.001)
This association was independent of baseline GDMT score
Results suggest a dose-dependent relationship between use of GDMT and risk of adverse outcomes
Results
The majority of patients with congenital heart disease and HFrEF did not receive GDMT uptitration, indicating suboptimal therapy.
67% of patients (approximately 520 of 778) did not receive GDMT uptitration (ΔGDMT score of 0 or less)
Only 258 of 778 patients (33%) had GDMT uptitration defined as ΔGDMT score >0
Median baseline GDMT score was 2 (interquartile range 1–3)
Authors identified this as representing 'suboptimal therapy, and opportunities for improvement'
What This Means
This research studied 778 adults who were born with heart defects (congenital heart disease) and also had a weakened heart pump (heart failure with reduced ejection fraction). Researchers looked at whether following standard heart failure treatment guidelines — called guideline-directed medical therapy or GDMT — was associated with better health outcomes, specifically fewer hospitalizations for heart failure and lower rates of death. They measured how much of the recommended therapy each patient was receiving at the start of the study and again one year later.
The study found that patients who were already on more of the recommended treatments had better outcomes, and patients who had their treatments increased over the year did even better. Specifically, each additional point of treatment score at baseline was associated with a 19% lower risk of heart failure hospitalization and a 15% lower risk of death. Increasing treatment over time was associated with a 30% lower hospitalization risk and an 18% lower mortality risk. These findings suggest that the more closely patients followed treatment guidelines, the better their outcomes — a pattern the researchers describe as a 'dose-dependent relationship.'
Despite these benefits, the study found that two-thirds of patients (67%) did not have their treatments increased over the one-year follow-up period, suggesting many patients are not receiving optimal care. This research suggests that more aggressive efforts to implement and increase guideline-recommended heart failure treatments in adults with congenital heart disease could meaningfully reduce hospitalizations and improve survival in this population, which has historically been understudied in heart failure treatment trials.
Ellabbad M, Kholeif Z, Dunlay S, Jokhadar M, Majdalany D, Egbe A. (2026). Clinical Benefits of Medical Therapy in Adults With Congenital Heart Disease and Systemic Left Ventricular Presenting With Heart Failure With Reduced Ejection Fraction.. Journal of the American Heart Association. https://doi.org/10.1161/JAHA.125.048260