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Cholinesterase Inhibitors Associated With Lower Mortality in Heart Failure With Preserved Ejection Fraction: a
Ming-Jer Hsieh1, Cheng-Hung Lee2, Dong-Yi Chen3
1Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan; Heart Failure Center, Chang Gung Memorial Hospital, Linkou, Taiwan. Electronic address: https://x.com/MJHsiehMD.
Insights
Cholinesterase inhibitors (ChEIs) significantly reduced mortality and heart failure hospitalizations in patients with heart failure with preserved ejection fraction (HFpEF). This suggests ChEIs may be a viable treatment for HFpEF.
Area of Science:
- Cardiology
- Pharmacology
- Medical Research
Background:
- Parasympathetic pathway modulation via vagal pathways is an underexplored treatment strategy for heart failure (HF).
- Cholinesterase inhibitors (ChEIs) enhance cholinergic tone and have demonstrated therapeutic benefits in HF patients.
- This study examines the impact of ChEI use on clinical outcomes in patients diagnosed with heart failure with preserved ejection fraction (HFpEF).
Purpose of the Study:
- To investigate the association between the use of Cholinesterase inhibitors (ChEIs) and clinical outcomes in patients with heart failure with preserved ejection fraction (HFpEF).
Main Methods:
- A retrospective cohort study utilized a multi-institutional database from July 2002 to December 2022.
- HFpEF was defined by left ventricular ejection fraction >50% and an H2FPEF score ≥6.
- 1:2 propensity score matching was applied, with primary endpoints including all-cause and cardiovascular mortality, and HF hospitalization over a 5-year follow-up.
Main Results:
- ChEI use was linked to significantly lower all-cause mortality (HR 0.45) and cardiovascular mortality (HR 0.41).
- Patients using ChEIs experienced fewer heart failure hospitalizations (HR 0.52) compared to nonusers.
- ChEI users showed a lower incidence of elevated left ventricular filling pressure (E/e' ≥13) (43.4% vs. 65.1%, p=0.010).
Conclusions:
- Cholinesterase inhibitor therapy in HFpEF is associated with substantial reductions in mortality and HF hospitalizations.
- Improved left ventricular filling pressure was observed in ChEI users.
- These findings warrant further prospective trials to evaluate ChEIs as a potential therapeutic option for HFpEF.
Background:
Modulating parasympathetic activity through vagal pathways represents a promising but underexplored strategy in heart failure (HF) treatment. Cholinesterase inhibitors (ChEIs), which enhance cholinergic tone by preventing acetylcholine degradation, have shown therapeutic value in patients with HF. In this study we investigate the association between ChEI use and clinical outcomes in patients with HF with preserved ejection fraction (HFpEF).
Methods:
We performed a retrospective cohort study using a multi-institutional database spanning July 2002 to December 2022. HFpEF was defined as left ventricular ejection fraction > 50% and an H2FpEF score ≥ 6. Following 1:2 propensity score matching, primary endpoints included all-cause and cardiovascular mortality, with HF hospitalization as a secondary endpoint over a 5-year follow-up. Echocardiographic parameters were compared between ChEI users and matched nonusers.
Results:
Among 11,862 HFpEF patients, 516 received ChEIs. After matching, 1242 patients (414 ChEI users and 828 nonusers, mean age 80.8 years, 64% women) were included in the analysis. ChEI use was associated with significantly lower all-cause mortality (hazard ratio [HR] 0.45, 95% confidence interval [CI] 0.36-0.57, P < 0.001), cardiovascular mortality (HR 0.41, 95% CI 0.26-0.65, P < 0.001), and HF hospitalization (HR 0.52, 95% CI 0.34-0.80, P = 0.003). Echocardiographic follow-up showed a lower incidence of elevated left ventricular filling pressure (E/e' ≥ 13) in ChEI users compared with nonusers (43.4% vs 65.1%, P = 0.010).
Conclusions:
ChEI therapy in HFpEF is associated with significant reductions in mortality and HF hospitalizations, alongside improved left ventricular filling pressure. These findings support further prospective trials to explore use of ChEIs as a potential therapeutic strategy in HFpEF.
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