In-hospital treatment intensification and outcomes in patients hospitalised for worsening heart failure in the current era of guideline-directed medical treatment

Background The real-world impact of intensifying contemporary guideline-directed medical therapy (GDMT) during hospitalisation on long-term outcomes in patients with heart failure (HF) remains uncertain. Purpose This study aimed to evaluate the association between in-hospital GDMT intensification and long-term outcomes in patients with HF, using data from the Quality of Heart Failure Care and Outcomes Registry Retrospective Cohort (QHEART-R) study, a multicentre registry of patients hospitalised for worsening HF from October 2020 through December 2024 at six institutions in Japan. Methods This Study included 3,190 patients hospitalised for worsening HF. In-hospital GDMT intensification was quantitatively assessed by the change in the Simple GDMT score from admission to discharge (∆S-GDMT). The primary outcome was a composite of cardiovascular (CV) mortality and hospitalisation for HF (HHF). Results The mean age was 77.7±14.0 years, 53% were male, and the mean left ventricular ejection fraction was 44.2±17.0%. The cohort comprised 1,401 HF with reduced EF (HFrEF; 44%), 511 HF with mildly reduced EF (HFmrEF; 16%), and 1,276 HF with preserved EF (HFpEF; 40%). The 4-year event-free survival rate for the primary composite outcome was 32.4%; for each component, 82.5% for CV mortality and 50.4% for the HHF. The incidence rate for HHF was higher in patients with HFpEF than those with HFrEF (p=0.023). ∆S-GDMT was independently associated with post-discharge CV mortality and HHF among patients with HFrEF and HFmrEF (adjusted hazard ratio: 0.88, 95% confidence interval: 0.84, 0.92, p<0.001). The high GDMT intensification group demonstrated significantly higher event-free survival compared with the modest intensification and the no intensification or diminution group (Figures 1A-1C). Restricted cubic spline model analyses revealed a graded, inverse association between ∆S-GDMT and the incidence of the composite outcome, CV mortality, and HHF (all p<0.0001), indicating that greater intensification of GDMT during hospitalisation for worsening HF was associated with more favorable clinical outcomes (Figures 2A-2C). Conclusions Despite contemporary GDMT implementation, HHF remains frequent. ∆S-GDMT was an independent predictor of post-discharge CV mortality and HHF among patients with HFrEF and HFmrEF. These findings suggest that hospitalisation represents a critical therapeutic window and underscore the importance of proactive GDMT intensification during hospitalisation, guided by a quantitative GDMT score, to improve long-term outcomes in patients with HFrEF and HFmrEF.