Short-Stay Units vs Routine Admission From the Emergency Department in Patients With Acute Heart Failure

Key Points Question Instead of hospital admission from the emergency department, does a short-stay unit (SSU) strategy of care improve quality of life for lower-risk patients with acute heart failure? Findings In this randomized clinical trial of 193 patients, there were no significant differences in quality of life at 30-day follow-up and no safety differences, although there were more days alive and out of hospital in the SSU arm. Outcomes were underpowered due to low enrollment during the COVID-19 pandemic. Meaning These findings show that for lower-risk patients with acute heart failure, SSUs may be a reasonable alternative to hospitalization.


Introduction
Health care utilization for acute heart failure (AHF) is an important patient and health services burden.In the US, approximately 6 million people have heart failure, 1 with mortality rates increasing since 2012 and hospitalization rates increasing in the past decade. 2The cost of heart failure is projected to increase from $3.7 billion in 2012 to $69.8 billion in 2030, with hospitalization for AHF being the greatest contributor. 1,3Hospitalization is also a marker for serious adverse events.
Compared with patients with chronic heart failure not hospitalized, the 1-year all-cause mortality rate is nearly 4 times higher for those who are hospitalized. 4Patients of lower socioeconomic status are disproportionately affected by both hospitalization and rehospitalization. 57][8] These potentially avoidable admissions are characterized by patients at lower risk for adverse events, such as those with higher blood pressure and lower natriuretic peptide levels. 8,9Hospitalizing or rehospitalizing such patients may unnecessarily expose them to in-hospital adverse events and reduced quality of life. 10rthermore, approximately 25% of discharged patients with AHF are rehospitalized within 30 days.
Safe alternatives to hospitalization are needed. 7,11,12[15] Prior work has shown a shorter length of stay in SSU patients compared with risk-matched inpatients (25.7 vs 58.5 hours), 13,14 but past studies were limited by their nonrandomized design.Thus, we designed the Using Short Stay Units Instead of Routine Admission to Improve Patient Centered Health Outcomes for Acute Heart Failure Patients (SSU-AHF) trial to overcome prior limitations and evaluate outcomes in the setting of a randomized trial.

Study Design
The SSU-AHF trial was a multicenter, randomized, comparative effectiveness study comparing 2 strategies of care for ED patients with AHF: SSU treatment vs hospitalization.The study was conducted between December 6, 2017, and July 22, 2021.
The SSU nomenclature was informed based on feedback from patient focus groups. 16,17To address the variability in SSU treatment across hospitals, we defined the intervention arm as observation or SSUs where the length-of-stay goal was less than 24 hours and patients were treated by ED clinicians.More in-depth details regarding the study design have been previously published. 18e COVID-19 pandemic required significant changes to the study design, including the primary All sites first obtained institutional review board approval prior to study enrollment.All patients provided written informed consent before randomization, and the study was registered with ClinicalTrials.gov(NCT03302910).This study followed the CONSORT reporting guideline. 19e Indiana University School of Medicine acted as the study coordinating center responsible for all study operations and data operations.An independent data safety monitoring board was created to ensure the safety of all trial participants.Adverse events were collected for the first 5 days after randomization.Each reported adverse event was described by its duration (ie, start and end dates); regulatory seriousness criteria, if applicable; and suspected relationship to the study protocol in accordance with definitions set forth by each institutional review board.In general, these relationships were categorized as likely, possible, unlikely, and not related.Adverse events were assessed via medical record review and during patient follow-up.

Study Population and Setting
The target population was lower-risk patients who presented to the ED with signs and symptoms of AHF.Final eligibility criteria are listed in eTable 1 in Supplement 2 and were modified from the original study protocol.Importantly, only patients who the ED clinician planned to hospitalize were eligible for enrollment.Patients were enrolled at 12 academic hospital sites in the following states: Indiana, Tennessee, Michigan, North Carolina, Pennsylvania, Ohio, Mississippi, Alabama, and Missouri (eTable 2 in Supplement 2).One site did not enroll any patients, as study start-up occurred proximate to the pandemic.

Randomization and Study Procedures
Race and ethnicity were obtained by the study team via self-report directly from the participants during the consent and randomization process.Eligible patients were randomized 1:1 to either hospital admission or SSU treatment through permuted block randomization (block sizes of 2, 4, and 6).Follow-up data were collected via telephone at 30 (±7) and 90 (±30) days post discharge from either the hospital or SSU (up to 120 total days after randomization per protocol).There were no further in-person visits required once discharged.Follow-up calls assessed vital status, all-cause rehospitalizations, ED revisits (via patient recall and electronic health record [EHR] search), and quality of life using the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12) short form.All decisions related to clinical testing and therapy were at the discretion of the clinical teams and were not dictated by study protocol. 18l SSU patients were monitored by telemetry.Four principles of SSU AHF management were outlined in the SSU management protocol 18 : (1) relief of heart failure symptoms and signs, (2)   decongestion and correction of any electrolyte imbalances, (3) hemodynamic improvement, and (4) robust care transitions with an emphasis on guideline-directed medication reconciliation and guideline-recommended therapy at discharge. 15,20,21Our management strategies were adapted from European Society of Cardiology and Society of Chest Pain Centers guidelines. 21We augmented these guidelines by providing greater detail regarding vasodilator and diuretic dosing.Vasodilators were suggested to be considered when congestion persisted and systolic blood pressure was greater than 135 mm Hg.The SSU discharge criteria were taken from the Society of Chest Pain Centers guidelines on observation unit care. 15Patients who had an acute event during their SSU stay or were not ready for discharge after the SSU management phase were hospitalized.
Hospitalization for AHF was chosen as the comparator.Acute heart failure treatment was left to the discretion of the inpatient care teams.In keeping with the pragmatic study design, each study arm used existing transitional care programs to assist with the postdischarge period.

JAMA Network Open | Cardiology
Short-Stay Units vs Routine Admission in Patients With Acute Heart Failure

Study Outcomes
The original primary outcome was days alive and out of hospital (DAOOH) at 30 days.Original study outcomes are listed in eTable 3 in Supplement 2. Because of the COVID-19 pandemic, we revised the enrollment goals and changed our focus to 1 of our secondary outcomes, quality of life, as measured by the KCCQ-12 short form. 22We anticipated adequate power based on prior data from other studies to change our primary focus to KCCQ-12 scores (eTable 4 in Supplement 2).The KCCQ-12 has been used in prior AHF studies and is sensitive to the patient's changing clinical condition, and a change of 5 points or more has been accepted as a clinically important difference. 23,24Prior work by our study group suggested that changes in KCCQ-12 scores are associated with rehospitalization. 23Thus, we hypothesized that SSU patients would have a greater quality of life due to fewer hospital days.Specifically, we hypothesized that the SSU strategy of care compared with hospitalization would lead to a significant improvement (Ն5 points) in quality of life scores at 30 days post discharge.After this change in our primary outcome, the original 30-day DAOOH became a secondary outcome.Other outcomes, such as caregiver burden assessments, were eliminated because families were not allowed to accompany patients in the hospital.

Statistical Analysis
Data analyses were performed between March 27, 2020, and November 11, 2023.In accordance with the intention-to-treat principle, participants were analyzed by the arm to which they were randomized (statistical analysis plan provided in Supplement 1).Patient baseline characteristics are presented using means (SDs) or medians (IQRs) for continuous variables or frequency and percentages as appropriate.Group comparisons of continuous variables were based on either 2-sample t tests (under normality) or Wilcoxon rank sum test.Categorical data comparisons are presented based on Fisher exact test.

KCCQ-12 Quality-of-Life Analysis
The KCCQ-12 mean score was compared between the 2 arms using a 2-sample t test.We analyzed the KCCQ-12 results 3 ways.First, patients who died without a KCCQ-12 score were excluded.Second, we set the KCCQ-12 to 0 for those who died without the 30-day KCCQ-12 score and include these participants in the analysis.Third, we created a composite binary end point of KCCQ-12 score less than c or death, where c is a threshold.We used both the 25th percentile and median for this threshold.We used t and Fisher exact tests to compare these outcomes.The 3 analysis schemes allowed us to understand how robust the comparison of KCCQ-12 scores is with respect to different thresholds of KCCQ-12 scores when death occurred.
To provide context for the responder analysis, we have included eTable 5 in Supplement 2 to summarize the baseline characteristics of KCCQ-12 responders in each treatment arm in order to facilitate assessment of the balance of the treatment groups among responders.The KCCQ-12 change scores were compared between the 2 arms using a 2-sample t test.

Secondary Analysis: DAOOH Outcome
The EHR time stamps were used to capture time of ED arrival, time leaving the ED, time of arrival to SSU or inpatient admission, and time of discharge.Any time spent in the ED, SSU, or inpatient admission was counted against the participant's DAOOH.If length of stay in the SSU was 29 hours, this time counted as 1.2 days.The DAOOH outcome includes time from randomization, capturing the index ED or hospital visit.Additional analyses are reported from time of discharge.The DAOOH was compared between the 2 treatment groups using a Wilcoxon rank sum test.
A composite outcome of all-cause mortality and rehospitalization was defined as the time from randomization to either all-cause death or rehospitalization at 30 and 90 days.The 2 treatments groups were compared using a log-rank test.To account for the influence of differences in site management, a stratified log-rank test was used.The Fisher exact test was used to compare the

JAMA Network Open | Cardiology
Short-Stay Units vs Routine Admission in Patients With Acute Heart Failure proportions of participants who had either all-cause mortality or rehospitalization within 30 and 90 days from randomization.
A 2-sided P < .05 was considered statistically significant without adjustment for multiple comparisons.Statistical tables and listings and analyses were produced using SAS, version 9.4 software (SAS Institute, Inc).

Participants
Starting December 6, 2017, through final follow-up on August 5, 2021, 194 patients were enrolled across 12 sites: 94 in the SSU arm and 100 in the hospitalization arm (with 1 participant found ineligible after randomization due to a protocol violation in the SSU arm) (Figure 1).Two patients died during hospitalization in the hospitalization arm.Of the 193 patients enrolled, the mean (SD) age was 64.8 (14.8) years; 79 (40.9%) were women and 114 (59.1%) men; of 192 with available data, 108 (56.3%) self-identified as Black, 2 (1.0%) as Hispanic or Latino, 80 (41.7%) as White, and 4 (2.1%) as other race (including 1 each of American Indian or Alaska Native, Arabic or Middle Eastern, Asian Indian, and Filipino).At baseline, characteristics between arms were similar (Table 1).Participants had a mean (SD) left ventricular ejection fraction (LVEF) of 36.8% (16.5%) in the SSU arm and 41.4% (15.3%) in the hospitalization arm (P = .12).There were numerically more patients with a reduced LVEF in the SSU arm.The treatment groups were similar in terms of baseline vital signs and laboratory values.There were no observed differences between the SSU and hospitalization arms with respect to the proportion of study patients receiving furosemide in the ED (87 [93.5%] vs 87 [87.0%];P = .15)or the total intravenous furosemide dose while in the ED (61.0 [30.4] vs 55. 5 [32.0]   mg; P = .26).There were also no differences in other initial ED therapy (eTable 6 in Supplement 2).

KCCQ-12 Quality-of-Life Outcome
Of the 193 participants randomized, 4 (4.3%) in the SSU arm and 4 (4.0%) in the hospitalization arm were lost to follow-up at 30 days, and 1 from the hospitalization arm withdrew from the study on day 3.At the time of SSU or hospital discharge, 91 participants (97.9%) in the SSU arm and 97 (97.0%) in the hospitalization arm completed the KCCQ-12, with mean (SD) scores of 35.5 (22.2) and 33.1 (23.1), respectively (P = .47).Table 2 shows the breakdown of the KCCQ-12 components at baseline (time of SSU or hospital discharge) and 30 days.In both arms (SSU, 64 participants; hospitalization, 67 participants), KCCQ-12 scores at day 30 improved from discharge to well above the 5 points  2A).When a composite binary end point of KCCQ-12 was created with KCCQ-12 less than c or death, where c is a threshold (we used both 25th percentile and median or equals 0 for deaths), there were also no significant differences.Figure 2B shows the analysis of KCCQ-12 responders by established thresholds of clinically important differences in KCCQ-12 scores. 24eTable 5 in Supplement 2 shows that the baseline characteristics of a Includes 2 patients who died during hospitalization.
b Only for participants with follow-up data.
c Log-rank P value tested time from randomization to the earlier of all-cause death or rehospitalization (in days).the KCCQ-12 responders were comparable between the treatment groups, with the exception of the categorized LVEF.

Secondary Outcome: DAOOH at 30 Days
No additional deaths occurred in either arm after hospital discharge through 30 days.Participants in the SSU arm had a significant 1.6 more DAOOH (median, 26.9 days; IQR, 24.4-28.8days) vs the hospitalization arm (median, 25.4 days; IQR, 22.0-27.7 days; P = .02)(Figure 3).There were no differences between arms for either 30-or 90-day all-cause death or rehospitalization.Table 2 shows the original primary outcome as well as other secondary outcomes of interest.eTable 8 in Supplement 2 shows 90-day secondary outcomes.

Other Outcomes
Of the participants randomized to the SSU arm, 39 (41.9%) required hospitalization after SSU treatment (eTable 9 in Supplement 2).None of the patients in the hospitalization arm crossed over to the SSU strategy.For participants who required hospitalization from the SSU (SSU treatment failure), their number of hospital days, including the ED stay, was greater than for those randomized to the hospitalization arm (median, 4.0 [IQR, 2.8-10.1]vs 3.1 [IQR 2.0-5.9]days; P = .03).When followed through 30 days, however, there was no significant difference in the number of days in the hospital and ED when counting the initial hospital stay (mean [SD], 7.6 [6.5] vs 5.6 [4.8] SSU vs hospitalization, respectively; P = .09).
A total of 7 deaths occurred in the study by 90 days, 3 in the SSU arm and 4 in the hospitalization arm (Figure 1), with only 1 death occurring within the adverse event monitoring period.In the SSU arm, 15 participants (16.1%) experienced an adverse event vs 16 (16.0%) in the hospitalization arm.

Discussion
In this multicenter, randomized clinical trial, no differences between SSU treatment and hospitalization were seen in KCCQ-12 scores at day 3.However, there was a significant increase in the number of DAOOH at 30 days in the SSU arm.While both treatment strategies resulted in clinically important changes in KCCQ-12 scores from baseline, lower-than-expected enrollment during the COVID-19 pandemic left the study underpowered to detect a significant difference between the strategies.There were no differences in adverse events between groups.Our findings build on past work where SSU as an alternative to hospitalization from the ED appeared to be a safe option in  Funding/Support: This project was supported by grant R01HS025411 from AHRQ.
Role of the Funder/Sponsor: The sponsor had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer:
The content is solely the responsibility of the authors and does not necessarily represent the official views of AHRQ.
Data Sharing Statement: See Supplement 3.

Additional Contributions:
The authors thank Shooshan Danagoulian, PhD (Wayne State University), for grant preparation.Dr Danagoulian received support from grant R01HS025411 from AHRQ as compensation for her contribution.The authors also thank Jan DeLaMare, MPAff, program officer at AHRQ for her years of support to this project.Ms DeLaMare did not receive compensation from the grant for her support.

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outcome and overall sample size.While patients were enrolled from the ED throughout the trial, during the pandemic, clinical research in the ED and use of the observation unit for patients with shortness of breath were either completely abandoned or used for different types of patients with COVID-19.When the trial resumed during the pandemic, clinical and research staffing challenges required reinitiation of start-up activities.As the pandemic waxed and waned, such activities JAMA Network Open | Cardiology Short-Stay Units vs Routine Admission in Patients With Acute Heart Failure occurred multiple times.When it became clear that enrollment projections would not reach prior goals used to inform sample size calculations, the study leadership, in consultation with the funding agency, made changes in the primary outcome based on a new enrollment projection.The original trial protocol is provided in Supplement 1.

Figure 3 .
Figure 3. Days Alive and Out of the Hospital Between Randomization and 30-Day Follow-Up 30

Table 2 .
Primary and Secondary Outcomes: 12-Item Kansas City Cardiomyopathy Questionnaire (KCCQ-12) at Baseline (Discharge) and 30-Day Follow-Up receiving research support from the National Institutes of Health and AHRQ outside the submitted work.Dr Bischof reported receiving subcontract grants from AHRQ during the conduct of the study and grants from the Patient-Centered Outcomes Research Institute, Beckman Coulter, QuidelOrtho, Comprehensive Research Associates, and RCE Technologies outside the submitted work.Dr Diercks reported receiving grants from Roche Abbott, Ortho-Clinical Diagnostics, and Siemens outside the submitted work.Dr Levy reported receiving personal fees from the American College of Cardiology and current grant funding from the National Institutes of Health (01 HL153607; R01 HL163377; R01 HL146059; R01 HL127215; P50 MD017351; and T32 HL120822); being a past chair of the American College of Cardiology (ACC) Accreditation Oversight Committee and a current member of the ACC NCDR Oversight Committee; and having served as a consultant for Astra Zeneca, Bayer, Novartis, BTG Specialty Pharmaceuticals, UltraSight Medical, HeartBeam, Hemisens, Cardionomics, Life Recovery Systems.Quidel, Siemens, Roche Diagnostics, Ortho Diagnostics, Beckman Coulter, Pathfast, and the Baim Institute outside the submitted work.Dr Miller reported receiving research support from the National Institutes of Health, AHRQ, and PCORI and serving as a consultant for AstraZeneca, Siemens, Beckman Coulter, Panafina, and BioXcel.Dr Venkat reported receiving grants from the National Institutes of Health during the conduct of the study.Dr Harrison reported receiving grants from the National Center for Advancing Translational Science, Abbott, Doris Duke Foundation, Indiana Clinical and Translational Sciences Institute, and Blue Cross Blue Shield Foundation of Michigan and personal fees from Vave Health and EB Medicine outside the submitted work.Dr Collins reported receiving personal fees from Reprieve Cardiovascular, Abbott Diagnostics, Boehringer Ingelheim, Siemens, and Aiphia and grants from the National Heart, Lung, and Blood Institute and Patient-Centered Outcomes Institute during the conduct of the study.No other disclosures were reported.