Key result
TARGET-HF evaluates whether tofogliflozin improves cardiac sympathetic nerve activity in HFrEF and T2DM.
Why the study?
SGLT2 inhibitors reduce heart failure hospitalizations in T2DM, but the mechanisms remain unclear, with modulation of cardiac sympathetic activity proposed as a potential contributor.
Does tofogliflozin improve cardiac sympathetic nerve activity in adults with HFrEF and T2DM?
Does tofogliflozin improve cardiac sympathetic nerve activity in adults with HFrEF and T2DM?
The TARGET-HF trial is designed to prospectively evaluate whether the SGLT2 inhibitor tofogliflozin improves cardiac sympathetic nerve activity, assessed by I-123 MIBG scintigraphy, in patients with HFrEF and T2DM.
Tofogliflozin effects on sympathetic activity in HFrEF with T2DM remain unproven; TARGET-HF leaves this hypothesis open for prospective testing.
BACKGROUND: Cardiac sympathetic nervous dysfunction is linked to poor prognosis in heart failure with reduced ejection fraction (HFrEF), and patients with HFrEF complicated by type 2 diabetes mellitus (T2DM) represent a particularly high risk. Sodium-glucose cotransporter-2 (SGLT2) inhibitors reduce heart failure (HF) hospitalizations in patients with T2DM, but the mechanisms underlying these benefits are not fully understood; modulation of cardiac sympathetic activity has been proposed as one contributor. The TARGET-HF trial will investigate whether tofogliflozin improves cardiac sympathetic nerve activity, assessed by I-123 metaiodobenzylguanidine (MIBG) scintigraphy, along with other cardiovascular parameters in patients with HFrEF and T2DM. METHODS: This single-arm prospective interventional study will enroll 50 patients with HFrEF (left ventricular ejection fraction < 40%), T2DM (hemoglobin A1c level, 6.5–10.0%), and estimated glomerular filtration rate ≥ 30mL/min/1.73 m². Participants will receive oral tofogliflozin (20 mg/day) for 24 weeks. The primary endpoint is the change in the heart-to-mediastinum ratio on delayed I-123 MIBG scintigraphy from baseline to 24 weeks. Secondary endpoints include changes in the early heart-to-mediastinum ratio, washout rate, echocardiographic parameters, and various biomarkers related to HF, inflammation, and metabolism. DISCUSSION: The TARGET-HF trial is the first interventional study to comprehensively evaluate the effects of tofogliflozin on cardiac sympathetic nerve activity using I-123 MIBG scintigraphy in patients with HFrEF and T2DM. By integrating nuclear imaging, echocardiography, and metabolic and biochemical biomarkers, this study aims to clarify the mechanisms underlying the cardioprotective effects of SGLT2 inhibitors. Improved understanding of these mechanisms may refine patient selection and guide targeted therapeutic strategies in HF management. TRIAL REGISTRATION: Japan Registry of Clinical Trials; approval number: jRCTs041210022 (February 6, 2021).
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Okumura et al. (2025) studied Heart failure with reduced ejection fraction and type 2 diabetes mellitus (n=50). Tofogliflozin was evaluated on Change in the heart-to-mediastinum ratio on delayed I-123 MIBG scintigraphy from baseline to 24 weeks. The TARGET-HF trial is a planned single-arm prospective interventional study designed to investigate whether tofogliflozin improves cardiac sympathetic nerve activity in patients with HFrEF and T2DM.
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