Association of Age With Guideline-Directed Medical Therapy and Left Ventricular Reverse Remodeling
- 1Seoul National University Bundang Hospital
Abstract
BackgroundComprehensive 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.
ObjectivesTo characterize age-related GDMT gaps and determine whether GDMT intensity is associated with left ventricular (LV) reverse remodeling across age and subsequent outcomes.
MethodsWe 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.
ResultsTriple/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.
ConclusionsOlder 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.
Related
- Heart Failure Progression in the Setting of Persistent Atrial Fibrillation, Frequent Premature Ventricular Complexes, and Malignancy-Related Limitations to Guideline-Directed Medical Therapy: A Case Report.
- Clinical Impact of Guideline-Directed Medical Therapy in Patients with Left Ventricular Assist Device: An International Multicenter Study
- Clinical and Social Determinants of Guideline-Directed Medical Therapy Optimization in Heart Failure with Reduced Ejection Fraction
- Digital and algorithmic strategies for guideline-directed medical therapy initiation and up-titration in adults with heart failure with reduced ejection fraction: a systematic review
- Improving Guideline-Directed Medical Therapy in Hospitalized HFrEF Patients
BibTeX
@misc{hwang2026association,
title = {{Association of Age With Guideline-Directed Medical Therapy and Left Ventricular Reverse Remodeling}},
author = {I.-C. Hwang and J. Park and N. Y. Bae and J. Lim and S. Kwak and M. Park and H.-M. Choi and J.-B. Park and Y. E. Yoon and S.-P. Lee and Y.-J. Kim and G.-Y. Cho and H.-K. Kim},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.04.26362221},
url = {https://www.medrxiv.org/content/10.64898/2026.09.04.26362221v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Association of Age With Guideline-Directed Medical Therapy and Left Ventricular Reverse Remodeling
AU - I.-C. Hwang
AU - J. Park
AU - N. Y. Bae
AU - J. Lim
AU - S. Kwak
AU - M. Park
AU - H.-M. Choi
AU - J.-B. Park
AU - Y. E. Yoon
AU - S.-P. Lee
AU - Y.-J. Kim
AU - G.-Y. Cho
AU - H.-K. Kim
PY - 2026
DA - 2026/09/04
PB - medRxiv
DO - 10.64898/2026.09.04.26362221
UR - https://www.medrxiv.org/content/10.64898/2026.09.04.26362221v1
AB - BackgroundComprehensive 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. ObjectivesTo characterize age-related GDMT gaps and determine whether GDMT intensity is associated with left ventricular (LV) reverse remodeling across age and subsequent outcomes. MethodsWe 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. ResultsTriple/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. ConclusionsOlder 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.
ER -