Delayed Initiation of ARNI and SGLT2i in Heart Failure With Corrected Aetiology (DELAY-HF), Pilot Study

Summary

In patients with heart failure due to a reversible underlying cause-such as valvular heart disease or coronary artery disease-surgical or procedural correction of the underlying lesion (valve repair/replacement, TAVI, PCI, or CABG) frequently leads to spontaneous recovery of cardiac function, even without neurohormonal modulators. In this clinical setting, a substantial proportion of patients may not require the full set of guideline-directed medical therapies routinely prescribed for chronic HFrEF. The purpose of this study is to determine whether ARNI (angiotensin receptor-neprilysin inhibitor) and SGLT2 inhibitors are truly necessary in patients whose left ventricular function recovers spontaneously after treatment of a correctable cause of heart failure.

The DELAY-HF trial (DELayed initiation of ARNI and SGLT2i in heart failure with corrected aetiologY) is a multi-center, randomized controlled non-inferiority trial evaluating whether a delayed-initiation strategy of ARNI and SGLT2i is non-inferior to immediate initiation in patients with heart failure whose underlying cause has been completely corrected by surgical or procedural intervention.

Adults with a preoperative left ventricular ejection fraction (LVEF) ≤40% who have undergone successful correction of a reversible cause of heart failure-either revascularization (PCI or CABG) for ischemic cardiomyopathy or valvular surgery (including TAVI) for left-sided valvular heart disease causing volume overload-will be randomized 1:1 to (1) delayed initiation, in which ARNI/SGLT2i are withheld for 6 months and started only in patients whose LVEF remains ≤40% at the 6-month assessment, versus (2) immediate guideline-directed medical therapy (GDMT) including ARNI/SGLT2i started shortly after the corrective procedure. All patients are followed for 12 months.

The primary outcome is the absolute change in LVEF from baseline at 12 months. Key secondary outcomes include cardiovascular mortality, heart failure hospitalization, additional echocardiographic indices, NT-proBNP, KCCQ quality-of-life score, 6-minute walk distance, and a cost-effectiveness analysis.

By comparing these two strategies, this trial will clarify the incremental contribution of ARNI and SGLT2i-both to further LVEF recovery and to clinical outcomes-in patients who have already demonstrated spontaneous improvement in cardiac function after correction of the underlying cause, and will thereby help define whether these agents are truly necessary in this population.

Conditions

• Heart Failure Due to Coronary Artery Disease
• Valvular Cardiomyopathy
• Heart Failure

Interventions

DRUG

Sacubitril / Valsartan

In the delayed-initiation arm, sacubitril/valsartan is withheld for 6 months after the corrective procedure; valsartan is used for blood pressure control and background heart failure therapy. At the 6-month assessment, sacubitril/valsartan is initiated only in patients with LVEF ≤40%. Patients with LVEF \>40% continue their existing regimen without ARNI. If heart failure worsens during observation (symptomatic deterioration or a ≥10 percentage-point drop in LVEF), sacubitril/valsartan is started immediately as rescue therapy. Patients on ARNI prior to enrollment undergo a 1-week washout before randomization.

DRUG

SGLT-2 inhibitor

In the delayed-initiation arm, the SGLT2 inhibitor (dapagliflozin 10 mg once daily or empagliflozin 10 mg once daily) is withheld during the first 6 months and initiated at the 6-month assessment only in patients whose LVEF remains ≤40%; patients whose LVEF has recovered to \>40% continue without SGLT2i under observation. If heart failure worsens during the observation period, the SGLT2 inhibitor is started immediately as rescue therapy. Patients receiving SGLT2i prior to enrollment undergo a 1-week washout before randomization.

DRUG

Sacubitril / Valsartan

In the immediate-initiation arm, sacubitril/valsartan is started within 7 days after the corrective procedure, once the patient is hemodynamically stable and euvolemic. The starting dose is selected based on baseline blood pressure (25 mg to 200 mg twice daily) and titrated to the maximally tolerated dose (target 200 mg twice daily), continued throughout the 12-month follow-up.

DRUG

SGLT2 Inhibition

An SGLT2 inhibitor (dapagliflozin 10 mg once daily or empagliflozin 10 mg once daily, at the discretion of the treating physician) is used as one of the foundational therapies of guideline-directed medical therapy for heart failure. In the immediate-initiation arm, the SGLT2 inhibitor is started after correction of the underlying cause of heart failure and continued throughout the 12-month follow-up.

Sponsors & Collaborators

• Seoul National University Bundang Hospital

  collaborator OTHER

• Korea University Anam Hospital

  collaborator OTHER

• Ajou University Medical Center

  collaborator UNKNOWN

• Kyungsub Song

  lead OTHER

Principal Investigators

• Kyungsub Song, MD · Keimyung University Dongsan Medical Center

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-05-20

Primary Completion

2028-05-20

Completion

2028-12-20

Countries

• South Korea

Study Locations