Traditional cardiovascular risk factors and guideline-directed medical therapy profile in ACHD living with HFrEF. a national referral centre study

Introduction The majority of adults with congenital heart disease (ACHD) who develop heart failure present with preserved ejection fraction. Evidence regarding heart failure with reduced ejection fraction (HFrEF) in this population remains limited, particularly in low- and middle-income countries. Purpose The aim of this study is to determine whether traditional cardiovascular risk factors and optimisation of guideline-directed medical therapy (GDMT) independently influence survival and HF hospitalisation burden in ACHD patients with HFrEF. Methods We conducted a retrospective cohort study at a tertiary referral centre in Mexico City (January 2021–December 2024). Baseline demographic, clinical and treatment data were obtained from institutional records. Primary outcomes were all-cause mortality and HF hospitalisations during follow-up. Cox proportional hazards models were used for time-to-event analyses; penalised Cox regression with Firth’s correction was applied in cases of complete event separation. Hospitalisation burden was assessed using multivariable negative binomial regression with follow-up time as an offset. GDMT optimisation was defined as (<3 versus ≥3 therapies). Multivariable models were adjusted for age, sex, LVEF, and NYHA class. Results are reported as hazard ratios (HR) and incidence rate ratios (IRR) with 95% CI. Results Among 2,662 ACHD patients, 147 (5.5%) had HFrEF and were included. During follow-up, 41 patients (27.9%) died. Traditional cardiovascular risk factors—including hypertension, diabetes, smoking, and atrial fibrillation—were not independently associated with mortality in multivariable analyses. Lower LVEF was independently associated with higher HF hospitalisation rates (IRR 0.96 per 1% increase; 95% CI 0.93–0.99; p=0.003). Seventeen patients (11.6%) received ≥3 GDMT agents; no deaths occurred in this group. After adjustment using penalised Cox regression with Firth’s correction to account for complete event separation, , ≥3 GDMT agents were independently associated with lower mortality (HR 0.06; 95% CI 0.0004–0.39; p=0.0004) and reduced HF hospitalisations (IRR 0.53; 95% CI 0.29–1.01; p=0.036). Conclusions In ACHD patients with HFrEF, traditional cardiovascular risk factors were not independently associated with mortality whereas lower LVEF emerged as the principal determinant of HF hospitalisation burden. Importantly, GDMT optimisation (≥3 agents) was strongly associated with improved survival and fewer HF admissions. These findings support the potential benefit of contemporary multidrug HFrEF therapy in ACHD, a population historically underrepresented in clinical trials. Our results are consistent with emerging real-world data in ACHD cohorts evaluating the feasibility and potential benefit of contemporary multidrug regimens, including ARNI and SGLT2 inhibitors. Nevertheless, prospective studies are warranted to confirm these associations and address residual confounding.Baseline_Image_9uoeb99uoeb99uoeACHD2