Association of Age With Guideline-Directed Medical Therapy and Left Ventricular Reverse Remodeling

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Background: Comprehensive guideline-directed medical therapy (GDMT) remains underused in older patients with HFrEF, but whether the potential for treatment-associated myocardial recovery is preserved with advancing age remains uncertain. Objectives: To characterize age-related GDMT gaps and determine whether GDMT intensity is associated with left ventricular (LV) reverse remodeling across age and subsequent outcomes. Methods: We studied 1,795 patients with HFrEF receiving angiotensin receptor-neprilysin inhibitor (ARNI)-based therapy in the multicenter STRATS-HF-ARNI registry. GDMT intensity was defined by the number of foundational therapies used during the first year after ARNI initiation. Serial LV remodeling and subsequent death or HF hospitalization were evaluated using multivariable models and a 1-year landmark analysis. Results: Triple/quadruple GDMT was achieved in 59.1%, 50.8%, 53.4%, and 43.0% of patients aged <60, 60-69, 70-79, and ≥80 years, respectively (P<0.001). Older age and renal dysfunction independently predicted less comprehensive GDMT. Each additional GDMT pillar was associated with greater improvements in LVEF (+1.23 percentage points; P=0.012) and LV global longitudinal strain (+0.32 percentage points; P=0.049) and greater reductions in LV volumes. Substantial remodeling remained evident at advanced age. Greater LV reverse remodeling predicted lower subsequent risk, and exploratory bootstrap analyses supported significant indirect associations between greater GDMT intensity and lower risk through all four LV remodeling measures. Conclusions: Older patients received less comprehensive GDMT despite preserved potential for LV reverse remodeling. Greater GDMT intensity was associated with greater myocardial recovery, which may represent a pathway to better prognosis. These findings support intensive GDMT implementation in older patients when clinically tolerated.

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