No More Excuses: Optimising Heart Failure Therapy in Adults With Congenital Heart Disease

Heart failure remains the greatest challenge in ACHD

Heart failure (HF) represents the principal cause of morbidity and mortality in adult congenital heart disease (ACHD), and the treatment of HF has been one of the greatest challenges of recent years. A diagnosis of HF is a life-changing event during the ACHD patient’s life, and it should warrant our full attention. As we all know, an evidence base for the treatment of ACHD-related HF is lacking, as ACHD patients have been excluded from landmark trials studying medical therapies for HF. Therefore, clinicians are currently forced to extrapolate from the conventional HF guidelines, which are based on evidence obtained solely from acquired heart disease cohorts, and studies specific to the ACHD population are much needed.

New evidence supporting guideline-directed medical therapy

The study by Ellabbad et al. set out to provide much-needed insights into the potential clinical benefit of guideline-directed medical therapy (GDMT) for ACHD-related HF (1). In this retrospective study, 778 ACHD patients with a systemic left ventricle in a biventricular physiology and heart failure with an ejection fraction <50 % were included. A strong aspect of the study was that the authors defined clinical benefit based solely on hard endpoints, namely HF hospitalisation and all-cause mortality. Moreover, GDMT was classified using a modified GDMT score, consisting of the four pillars of GDMT (beta blockers, ACEi/ARB/ARNI, MRA, and SGLT2i), and including a dose target to allow evaluation of uptitration.

They found that every point increase in the baseline GDMT score was associated with a 19% reduction in heart failure hospitalizations (HR 0.81, 95% CI, 0.74–0.88, P<0.001) and a 15% reduction in mortality (adjusted HR 0.85, 95% CI, 0.76–0.94, P<0.001). Investigating the effect of uptitration of GDMT, they even found that every unit increase in the delta of the GDMT score during follow-up was associated with a 30% reduction in HF hospitalisation risk (adjusted HR 0.70, 95% CI, 0.61–0.79, P<0.001), and a 18% lower risk of mortality (adjusted HR 0.82, 95% CI, 0.71–0.94, P<0.001).

These findings are important to the ACHD community, providing robust evidence of the clinical benefit of HF pharmacotherapy in ACHD-related HF. They even point towards a dose-dependent relationship, suggesting that GDMT uptitration has additional benefit. Interestingly, two-thirds of patients did not have uptitration of their GDMT during follow-up, suggesting that there was significant room for improvement. The authors found similar associations in their subgroup analysis for patients with NT-proBNP and cardiac catheterisation data, and while higher baseline GDMT score was not significantly associated with mortality in patients with a cardiac implantable electronic devices, the delta of the GDMT score during follow-up was. Still, only 13% of patients used an MRA, 10% an SGLT2i, and 9% an ARNI in the study. With recent studies showing promising results in these newer medication groups, there might even be more benefit of GDMT (2, 3). 

Of note, another study was published by the same group two months before, showing that along with these improvements in hard endpoints, GDMT uptitration was also associated with a temporal improvement in LVEF, reduction in NT-proBNP, and lower 10-year incidence of mortality or heart transplantation, further supporting these findings (4).

Important limitations and future directions

Both studies only included patients with a systemic left ventricle and reduced ejection fraction, underscoring the anatomical complexity in ACHD care. Evidence for GDMT has not been consistently shown in challenging groups such as systemic right ventricle and Fontan circulation patients, and the next focus should be to investigate whether these positive results also extrapolate to these groups. Additionally, while the majority of patients included fell in the HF with mildly reduced ejection fraction (41–49%) group, patients with preserved ejection fraction (HFpEF) were excluded. Recent research has demonstrated that the prevalence of HFpEF is higher in the ACHD population than in the general population, highlighting the need for awareness and treatment strategies for HFpEF (5).

Take-home message

To conclude, Ellabbad and colleagues have provided an important link between medical therapy for HF and hard clinical endpoints, supporting the implementation of GDMT and active uptitration in ACHD patients with a systemic LV.