U-shaped relationship between guideline-directed medical therapy initiation timing and long-term adverse outcomes in acute heart failure

Abstract

Aim: The early initiation of guideline-directed medical therapy (GDMT) in patients with acute heart failure (AHF) is significantly associated with clinical prognosis. However, the optimal timing for initiating GDMT in AHF patients requiring Intensive Care Unit (ICU) admission remains unclear. This study aims to investigate the association between the timing of GDMT initiation and prognosis in ICU patients with acute heart failure.

Methods: This study identified ICU-admitted AHF patients from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database and determined GDMT initiation timing based on clinical treatment context. Patients were categorized into three groups according to the timing of GDMT initiation. Primary endpoints were 1-year all-cause mortality and the composite endpoint of 1-year all-cause mortality and heart failure rehospitalization. Cox proportional hazards regression and restricted cubic splines were utilized to elucidate the association between GDMT initiation timing and long-term adverse outcomes in patients with acute heart failure.

Results: A total of 7,002 patients were included in this study, of whom 4,260 (60.7%) received GDMT within one day after AHF onset. Compared to patients who initiated GDMT between one and four days, those who received GDMT within one day and those who received GDMT after four days had a higher composite risk of one-year all-cause mortality and heart failure rehospitalization. The restricted cubic spline analysis demonstrated a U-shaped relationship between GDMT initiation timing and the primary outcome. The composite risk of one-year all-cause mortality and heart failure rehospitalization decreased as GDMT initiation was delayed, reaching its lowest point around two days, after which the risk began to rise and eventually stabilized.

Conclusion: In critically ill acute heart failure patients, a nonlinear U-curve relationship emerged between GDMT initiation timing and all-cause mortality. The optimal therapeutic window diverges across patient subgroups defined by clinical characteristics, notably warranting individualized timing strategies - particularly in geriatric populations.

Keywords

Acute heart failure / guideline-directed medical therapy / intensive care unit / mortality / hemodynamic / geriatric populations / individualized treatment

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