What is the clinical evidence from this study?

Study design: Observational. Population: Heart failure with chronic arrhythmias (n=87). Intervention: Bucladesine calcium combined with metoprolol vs. Metoprolol tartrate alone. Primary outcome: Change from baseline in SDNN at 12 weeks (Mean difference 13.63 ms, 95% CI 4.17-23.09, p=0.005).

What question did this study set out to answer?

This study aims to evaluate whether bucladesine calcium enhances heart rate variability and cardiac function when combined with metoprolol in heart failure patients with arrhythmias.

May 8, 2026Open Access

Effect of bucladesine calcium combined with metoprolol on heart rate variability and cardiac function prognosis in heart failure patients with chronic arrhythmias

Key Result

Bucladesine calcium combined with metoprolol significantly improved heart rate variability, increasing SDNN by a mean difference of 13.63 ms compared to metoprolol alone in heart failure patients.

Key Points

This study aims to evaluate whether bucladesine calcium enhances heart rate variability and cardiac function when combined with metoprolol in heart failure patients with arrhythmias.
Single-center retrospective observational study of 87 patients with heart failure and chronic arrhythmias.
Patients received either metoprolol alone (n=41) or bucladesine calcium plus metoprolol (n=46) for 12 weeks.
Primary outcome was the change from baseline in heart rate variability time-domain parameters.
The combination group experienced a significant increase in ΔSDNN (mean difference 13.63 ms, 95% CI (4.17, 23.09), P=0.005).
Significant improvement in ΔLVEF was observed (4.86%, 95% CI (1.31, 8.41), P=0.008).
ΔRMSSD improved significantly (8.94 ms, 95% CI (2.80, 15.08), P=0.005).

Study Design

Type

Observational (n=87)

Multicenter

Structured PICO

Does adding bucladesine calcium to metoprolol improve heart rate variability and cardiac function in patients with heart failure and chronic arrhythmias?

Population

87 patients with heart failure (HF) and chronic arrhythmia (NYHA class II-IV), mean age ~52, ~57% male, treated at a single center in China. Key inclusion: confirmed HF diagnosis and chronic arrhythmia, clinically stable for ≥4 weeks.

Intervention

Bucladesine calcium 40 mg intravenous infusion once daily combined with metoprolol tartrate (titrated to target 25 mg bid or max tolerated) and standard HF management for 12 weeks.

Comparator

Metoprolol tartrate alone (titrated to target 25 mg bid or max tolerated) and standard HF management for 12 weeks.

Outcome

Change from baseline in heart rate variability (HRV) time-domain parameters (SDNN and RMSSD) at 12 weeks.surrogate

Main Result

Effect estimate: Mean difference 13.63 ms (95% CI 4.17-23.09)

Absolute Event Rate: 22.23% vs 8.6%

p-value: p=0.005

Limitations

Retrospective, non-randomized design introduces selection bias
Small sample size insufficient for sensitivity analyses
Metoprolol tartrate was used rather than the succinate formulation with established mortality benefit
Target beta-blocker dose remained below international guideline recommendations
Requirement for daily intravenous bucladesine over 12 weeks restricts clinical applicability
12-week follow-up was insufficient to assess hard endpoints such as mortality and major adverse cardiac events

Abstract

Background Heart failure (HF) with chronic arrhythmias is associated with autonomic dysfunction and poor outcomes. Heart rate variability (HRV) reflects autonomic dysfunction and predicts outcomes in HF. This study investigated whether adding bucladesine calcium to metoprolol improves HRV and cardiac function compared with metoprolol alone. Methods This single-center retrospective observational study included 87 patients with HF and chronic arrhythmia treated between January 2023 and April 2024. Patients received metoprolol tartrate alone (control group, n = 41) or bucladesine calcium combined with metoprolol (observation group, n = 46) for 12 weeks. The primary outcome was change from baseline in HRV time-domain parameters. Between-group differences were compared with 95% confidence intervals. Exploratory sensitivity and multivariable-adjusted analyses were performed. Results Baseline characteristics were comparable between groups. The combination group showed significantly greater improvements in ΔSDNN mean difference 13.63 ms, 95% CI (4.17, 23.09), P = 0.005 and ΔRMSSD 8.94 ms, (2.80, 15.08), P = 0.005. ΔLF/HF showed a borderline difference ( P = 0.043). ΔLVEF was significantly greater 4.86%, (1.31, 8.41), P = 0.008, as was ΔCO ( P = 0.019), while ΔLVEDd did not differ significantly ( P = 0.395). The overall response rate was numerically higher (89.1% vs. 78.0%) but not statistically significant ( P = 0.266). Adverse event rates were comparable. After multivariable adjustment, ΔSDNN ( P = 0.037) and ΔRMSSD ( P = 0.042) remained significant, while ΔLVEF became borderline ( P = 0.062). Conclusion Adding bucladesine calcium to metoprolol was associated with greater improvements in HRV time-domain parameters and LVEF, though effects were attenuated after covariate adjustment.

Bookmark

View Full Paper