The prognostic significance of pharmacological therapy after cardiac resynchronization therapy

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Heart failure with reduced ejection fraction (HFrEF) (n=272). Intervention: Baseline β-blocker use vs. Non-use of β-blockers. Primary outcome: Cardiac death or left ventricular assist device (LVAD) implantation (HR 0.252, 95% CI 0.071-0.891, p=0.032).

Q: What does this research mean for the field?

Baseline use of β-blockers and RAS inhibitors or ARNIs is independently associated with a significantly lower risk of cardiac death or LVAD implantation in patients receiving cardiac resynchronization therapy. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

T Sato; S. Murota; Minoru Nodera; Shinya Yamada; Takashi Kaneshiro; Takafumi Ishida; Yasuchika Takeishi

doi:10.5387/fms.25-00040

January 1, 2026FUKUSHIMA JOURNAL OF MEDICAL SCIENCEOpen Access

The prognostic significance of pharmacological therapy after cardiac resynchronization therapy

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Key result

Baseline use of β-blockers was independently associated with a significantly lower risk of cardiac death or LVAD implantation (HR 0.252) in patients undergoing cardiac resynchronization therapy.

Why the study?

Pharmacological therapy is essential in HFrEF, but its prognostic role at the time of CRT remains uncertain.

Does baseline pharmacological therapy improve the composite of cardiac death or LVAD implantation in patients with HFrEF undergoing CRT?

Key Points

To evaluate the prognostic impact of baseline pharmacological therapy use and dosing on long-term outcomes in patients undergoing cardiac resynchronization therapy (CRT).
Retrospectively analyzed 272 patients (mean age 66.4 ± 11.8 years, 71.7% male) with heart failure who underwent CRT between 2005 and 2023.
Assessed baseline medications including β-blockers (97.4%), RAS inhibitors/ARNIs (81.3%), MRAs (64.7%), and loop diuretics (76.8%), tracking patients over a median follow-up of 4.2 years.
Evaluated the primary outcome of cardiac death or left ventricular assist device (LVAD) implantation and the secondary outcome of all-cause death or LVAD implantation using multivariable Cox proportional hazards models.
During a median follow-up of 4.2 years, 126 patients (46.3%) reached the primary endpoint of cardiac death or LVAD implantation, and 154 patients (56.6%) experienced all-cause death or LVAD implantation.
Multivariable Cox regression demonstrated that baseline β-blocker use (HR 0.252, 95% CI 0.071-0.897), higher β-blocker dose (HR per 1 mg/day: 0.959, 95% CI 0.923-0.996), and RAS inhibitor/ARNI use (HR 0.562, 95% CI 0.351-0.897) were independently associated with a lower risk of the primary endpoint.
Higher loop diuretic dose exhibited a borderline association with increased risk (HR 1.006, 95% CI 1.000-1.013), while inotrope use was linked to worse prognosis, and baseline medications were not significantly associated with 1-year echocardiographic CRT response.

Study Design

Type

Cohort (n=272)

Multicenter

No

Structured PICO

Does baseline pharmacological therapy improve the composite of cardiac death or LVAD implantation in patients with HFrEF undergoing CRT?

P

Population

272 patients (mean age 66.4 years, 28.3% female) with heart failure with reduced ejection fraction undergoing cardiac resynchronization therapy, followed for a median of 4.2 years.

E

Exposure

Baseline pharmacological therapy (β-blockers, RAS inhibitors/ARNIs, MRAs, loop diuretics, intravenous inotropes) and their doses at the time of CRT implantation.

C

Comparator

Non-use or different doses of the respective pharmacological therapies.

O

Outcome

Composite of cardiac death or left ventricular assist device (LVAD) implantation.composite

Main Result

Hazard Ratio: 0.252 (95% CI 0.071–0.891)

p-value: p=0.032

Limitations

Retrospective single-center study design limits generalizability and precludes causal inference.
Medication use was assessed only at baseline, so dose-response associations reflect initial prescriptions rather than long-term exposure, adherence, or titration.
CRT response was defined solely by echocardiographic remodeling and did not include functional or quality-of-life measures.
Contemporary agents such as ARNIs, SGLT2 inhibitors, and vericiguat were introduced late in the study period and prescribed to a minority of patients.
Arrhythmic events and device therapies were not systematically collected, and residual confounding cannot be excluded.
Retrospective single-center study, which may limit generalizability, and causal inference cannot be established
Medication use was assessed only at baseline, so titration, adherence, and discontinuation patterns were not available
CRT response was defined solely by echocardiographic remodeling and did not include functional or quality-of-life measures
Contemporary agents such as ARNIs, SGLT2 inhibitors, and vericiguat were introduced relatively late in the study period and were prescribed to only a minority of patients

Implication

Baseline use and higher doses of β-blockers and RAS inhibitors/ARNIs at the time of CRT implantation are strongly associated with improved long-term survival free from LVAD implantation in patients with HFrEF.

Abstract

BACKGROUND: Pharmacological therapy is essential in heart failure with reduced ejection fraction (HFrEF), but its prognostic role at the time of cardiac resynchronization therapy (CRT) remains uncertain. METHODS: We retrospectively studied 272 patients (mean age 66 years;72% male) who underwent CRT between 2005 and 2023. Pharmacological therapy was assessed only at baseline. Medication included β-blockers (97.4%), renin-angiotensin system inhibitors or angiotensin receptor-neprilysin inhibitors (RAS inhibitors/ARNIs, 81.3%), mineralocorticoid receptor antagonists (64.7%), and loop diuretics (76.8%). The primary outcome was cardiac death or left ventricular assist device (LVAD) implantation. Cox models evaluated associations between baseline medication use, medication doses, and outcomes. RESULTS: During a median follow-up of 4.2 years, 126 patients (46.3%) experienced the primary outcome. Baseline use and higher β-blocker dose were independently associated with a lower risk of the primary outcome. RAS inhibitors/ARNIs use was also associated with a lower risk of cardiac death or LVAD implantation. In contrast, higher loop diuretic dose and inotrope use tended to be associated with worse outcomes. CONCLUSION: Baseline use and dosing of β-blockers and RAS inhibitors/ARNIs were prognostically significant in CRT recipients, underscoring the importance of optimizing pharmacotherapy at the time of device implantation.

Discussion

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Cite This Study

Sato et al. (2026) conducted a cohort in Heart failure with reduced ejection fraction (HFrEF) (n=272). Baseline β-blocker use vs. Non-use of β-blockers was evaluated on Cardiac death or left ventricular assist device (LVAD) implantation (HR 0.252, 95% CI 0.071-0.891, p=0.032). Baseline use of β-blockers was independently associated with a significantly lower risk of cardiac death or LVAD implantation (HR 0.252) in patients undergoing cardiac resynchronization therapy.

synapsesocial.com/papers/69edab424a46254e215b35a0 https://doi.org/10.5387/fms.25-00040

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The prognostic significance of pharmacological therapy after cardiac resynchronization therapy

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

The prognostic significance of pharmacological therapy after cardiac resynchronization therapy

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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