This will be a prospective, cluster-randomized, crossover, non-inferiority trial of 250 participants within 48 hours of an inpatient admission for heart failure or emergency department presentation for heart failure with plans for admission or observation/short-stay hospitalization comparing early discharge using subcutaneous furosemide to standard inpatient care. Individual practice groups will serve as "clusters" and the unit of randomization. Each participating cluster will implement either the early discharge strategy using the intervention or standard care for initial two-month blocks, followed by a crossover to the alternate strategy. The primary outcome is days alive and out of hospital at 30 days.

HF contributes to over 1 million emergency department visits and nearly 1 million hospitalizations annually. The estimated annual mean cost per person with HF was $32,955 in 2017-2018, with the majority of costs due to hospitalization. The current standard of care typically involves admission for intravenous (IV) diuretics, monitoring for adequate decongestion, transition to oral diuretics, and discharge once clinical stability is achieved. The median length of stay for HF hospitalizations in the United States is 5 days but varies significantly across health systems and at the patient level. Extended hospitalizations, while traditionally considered necessary for complete decongestion, carry substantial risks, including increased risk of all-cause death and readmission. Patients experience deconditioning and increased frailty and are at risk for hospital-acquired complications, including infections, falls, and cognitive decline. Furthermore, prolonged hospitalization can lead to post-hospital syndrome, characterized by increased vulnerability and risk for adverse events in the immediate post-discharge period. For these reasons, reducing length of stay has emerged as a critical goal in HF management, aimed at both decreasing costs and improving patient outcomes by minimizing hospital-related complications and preserving quality of life.

Recent developments in subcutaneous furosemide formulations offer a potential solution to this clinical challenge. Pharmacokinetic studies demonstrate that subcutaneous furosemide achieves bioavailability comparable to IV administration and superior to oral formulations. The consistent absorption profile and reliable bioavailability of subcutaneous furosemide, combined with its ease of administration, presents an opportunity to provide hospital-level diuresis in the outpatient setting. This could enable earlier discharge while maintaining the intensity of diuretic therapy needed for complete decongestion. However, a critical knowledge gap exists regarding the safety and efficacy of an early discharge strategy utilizing subcutaneous furosemide compared to traditional inpatient management.

This trial aims to address this knowledge gap through a cluster-randomized crossover study comparing early discharge with subcutaneous furosemide to standard inpatient care and receipt of IV furosemide. By implementing standardized protocols across two major health systems, the investigators will evaluate whether this novel approach can safely reduce length of stay while maintaining clinical outcomes. The study design accounts for institutional variations in care delivery while providing robust data on safety, efficacy, and resource utilization. Results from this trial could fundamentally change the management paradigm for acute heart failure hospitalizations, potentially improving both healthcare efficiency and patient outcomes.

Inclusion Criteria:

• Age ≥ 18 years
• Within 48 hours of inpatient stay OR ED presentation for HF with plans for admission OR observation stay/short-stay hospitalization for HF
• Expected to require at least 24 additional hours of IV diuretics
• Adequate home environment for self-care
• Patient or caregiver capable of operating subcutaneous delivery device

Exclusion Criteria:

• Cognitive impairment preventing informed consent
• Geographic barriers to follow-up
• Pregnancy or breastfeeding
• IV furosemide requirement >250mg/day
• eGFR <20 mL/min/1.73m2
• Type 1 myocardial infarction during index admission
• End-stage HF with receipt or consideration of heart transplant or LVAD or requiring inotropic or mechanical circulatory support
• Potassium <3.0 or >6.0 mmol/L or sodium <125 mmol/L