B-lines Lung Ultrasound Guided ED Management of Acute Heart Failure Pilot Trial (BLUSHED-AHF)

Nearly 80% of acute heart failure (AHF) patients admitted to the hospital are initially treated in the emergency department (ED). Once admitted, within 30 days post-discharge, 27% of patients are re-hospitalized or die. Attempts to improve outcomes with novel therapies have all failed. The evidence for existing AHF therapies are poor: No currently used AHF treatment is known to improve outcomes. ED treatment is largely the same today as 40 years ago. Congestion, such as difficulty breathing, weight gain, and leg swelling, is the primary reason why patients present to the hospital for AHF. Treating congestion is the cornerstone of AHF management. Yet half of all AHF patients leave the hospital inadequately decongested. The investigators propose a novel approach to aggressively decongest patients in the ED setting: lung ultrasound guided, protocol driven, AHF management. LUS B-lines are a measure of extra-vascular lung water (EVLW). In the setting of AHF, LUS B-lines are a measure of congestion. This simple, easily learned technique has excellent reliability and reproducibility. The investigators hypothesize that a strategy-of-care will outperform usual care. At the present time, usual care is largely empirical. This study will improve the evidence base for ED AHF management. This proposed pilot study, if successful, will lead to an outcome trial examining whether an ED AHF strategy-of-care increases days alive and out of the hospital for patients.

Study Overview

• Status: Completed
• Conditions: Heart Failure; Acute Cardiac Failure; Acute Cardiac Pulmonary Edema; Heart Failure Acute
• Intervention / Treatment: Other: LUS-guided strategy-of-care; Drug: Intravenous Loop Diuretic; Drug: Vasodilator; Device: Non invasive Ventilation (NIV); Other: Usual Care

Detailed Description

The primary goal of the BLUSHED AHF pilot trial is to determine whether an early lung ultrasound (LUS) guided, protocol-driven ED AHF strategy-of-care leads to more rapid and sustained resolution of congestion, as measured by LUS B-lines. If the investigators are able to demonstrate this necessary and sufficient information - targeted strategy-of-care is more effective than usual care - they will apply for a follow on study to achieve the following aim.

Aim 1: To demonstrate the effectiveness of a targeted decongestion strategy - LUS guided, protocol-driven ED AHF management - will result in improved 30-day outcomes vs. usual care. This aim will be tested using a randomized, controlled, unblinded, pragmatic, multi-center, simple trial design.

The pilot trial may determine that ED management alone is insufficient to impact the outcome. Thus, the investigators may need to modify their subsequent trial design to include targeted therapy throughout hospitalization. However, the pilot study will demonstrate whether targeted therapy effectively reduces B-lines.

PUBLIC HEALTH IMPACT Over one million hospitalizations for AHF occur every year in the US. Within 30 days after hospitalization, over 25% of AHF patients will be dead or re-hospitalized.4 Up to 67% of patients will be re-hospitalized and 36% will be dead by one year. For patients aged 65 years and older, AHF is the most common and most expensive reason for hospitalization. Despite major reductions in morbidity and mortality for chronic HF, considerably less progress has been seen in AHF.

Congestion is the primary reason why AHF patients present to the ED seeking medical care. Congestion is manifest by signs and symptoms of heart failure (HF); dyspnea, orthopnea, edema, and weight gain. Yet, how to best assess, grade, and manage congestion is not well established.

Freedom from congestion is associated with improved outcomes; Yet many patients leave the hospital inadequately decongested. The absence of robust, reliable methods to assess congestion is a primary reason why it is not well-assessed. A recent consensus statement published in 2010 highlights this fact: "…no method to assess congestion…has been validated." The investigators would argue many ED AHF patients are poorly assessed prior to treatment. In addition, they are poorly re-assessed prior to hospitalization to gauge the success or failure of initial management. While physical exam is currently the cornerstone of congestion assessment, it lacks sensitivity and inter-rater reliability.

The investigators challenge the current paradigm of relying on insensitive methods of congestion to guide therapy. Furthermore, they argue the lack of a robust evidence base for ED management of congestion contributes to poor outcomes.

• Study Type: Interventional
• Enrollment (Actual): 130
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • IU Health Methodist Hospital
    • Indianapolis, Indiana, United States, 46202
      • Eskenazi Health
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Detroit Receiving Hospital
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
  • Tennessee
    • Nashville, Tennessee, United States, 37235
      • Vanderbilt University
  • Virginia
    • Fairfax, Virginia, United States, 22042
      • Inova Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 21 years
• Presents with shortness of breath at rest or with minimal exertion
• Clinical diagnosis of AHF and presence of > 15 total bilateral B-lines distributed in at least 4 zones on initial LUS

• Hx of chronic HF and any one of the following:

  • Chest radiograph consistent with AHF
  • Jugular venous distension
  • Pulmonary rales on auscultation
  • Lower extremity edema

Exclusion Criteria:

• Chronic renal dysfunction, including end-stage renal disease (ESRD) or estimated glomerular filtration rate (eGFR) < 45ml//min/1.73m2.
• Shock of any kind. Any requirement for vasopressors or inotropes.
• Systolic blood pressure (SBP) < 100 or >175 mmHg
• Need for immediate intubation
• Acute Coronary Syndrome- Presentation consistent with myocardial ischemia AND either new ST-segment elevation/depression
• Fever >101.5 ºF or chest radiograph or clinical picture of pneumonia
• End stage HF: transplant list, ventricular assist device
• Anemia requiring transfusion
• Known interstitial lung disease
• Suspected acute lung injury or acute respiratory distress syndrome (ARDS)
• Pregnant or recently pregnant within the last 6 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LUS-guided strategy-of-care; Patients randomized to the LUS strategy of care arm will be treated according to protocol. This protocol only involves therapies used in everyday AHF clinical practice.	Other: LUS-guided strategy-of-care; For patients randomized to the strategy-of-care arm, the LUS guided protocol will be initiated and continued until there is a decrease in B-lines to ≤ 15 or 6 hours of care has been delivered, whichever comes first. Treatment protocol: IV furosemide (unless already given): 2x single oral dose if on chronic therapy or 20-40 mg if diuretic naive.; Optional therapies: non-invasive ventilation, vasodilators (SL, topical, or IV); Reassessment every 2 hours; Drug: Intravenous Loop Diuretic; IV loop diuretic; Drug: Vasodilator; IV, topical, or SL Vasodilator; Device: Non invasive Ventilation (NIV); Face, mouth, or nasal mask applied to provide positive pressure ventilation
Placebo Comparator: Usual care; Patients randomized to the usual care arm will also undergo lung ultrasound assessments. However, these results will not be revealed to the care team. Patients will receive treatment per usual, standard care.	Drug: Intravenous Loop Diuretic; IV loop diuretic; Drug: Vasodilator; IV, topical, or SL Vasodilator; Device: Non invasive Ventilation (NIV); Face, mouth, or nasal mask applied to provide positive pressure ventilation; Other: Usual Care; Patients will receive usual AHF care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With B-lines ≤ 15 at the Conclusion of ED AHF Management	B-lines ≤ 15 at the conclusion of ED AHF management or maximum of 6 hours after enrollment, whichever comes first.	During the ED phase of management, usually no more than 6 hours

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Days Alive and Out Of Hospital (DAOOH)	Total days alive and out of hospital through 30 and 90 days post-discharge	Up through 90 days, with specific reporting of events through 30 and 90 days
Association of B-lines at Discharge and 30-day / 90-day Outcomes		Up through 90 days, with specific reporting of events through 30 and 90 days
Change in Biomarkers From Presentation to Pre-discharge		From admission to pre-discharge from the hospital, on average 5 to 7 days.
Time to Reach B-lines <15		Throughout hospitalization, on average 5-7 days
B Lines < 15 at 24 Hours and at Discharge		Through the first 24 hours and then prior to discharge, on average 5-7 days after admission
Composite of 30-day and 90-day All-cause Mortality, Cardiovascular (CV) Re-hospitalizations, and CV Emergency Department (ED) Revisits.	CV endpoints are defined according to the 2014 American College of Cardiology/American Heart Association (ACC/AHA) Key Data Elements and Definitions for Cardiovascular Endpoint Events.	Up through 90 days, with specific reporting of events through 30 and 90 days
All Cause Readmissions, All Cause ED Re-visits	30- day and 90-day	Up through 90 days, with specific reporting of events through 30 and 90 days
Number of Participants With Physical Exam Findings of Heart Failure When Discharge is Compared to Baseline	Physical exam includes body weight, peripheral edema, jugular venous distention, pulmonary and cardiac auscultation	From admission throughout hospitalization, usually 5-7 days.
Count of Pharmacologic Therapies the Patient Received in the ED	This is a description of which pharmacologic therapies the patient has received.	From admission throughout hospitalization, usually 5-7 days.
Count of Pharmacologic and Device Therapies the Patient Received During Hospitalization	This is a description of which pharmacologic and device therapies the patient has received.	From admission throughout hospitalization, usually 5-7 days.
Comparison of LUS Interpretation Within and Between Trained Investigators as Well as the Core Lab	Calculation of intra and inter-agreement between investigators and also the Core Lab to determine the reproducibility of LUS	From admission throughout hospitalization, usually 5-7 days.
Association of Baseline, Discharge, and Change With 30 and 90 Day Outcomes		Up through 90 days, with specific reporting of events through 30 and 90 days

Collaborators and Investigators

• Sponsor: Indiana University
• Collaborators: Wayne State University; Vanderbilt University; Case Western Reserve University; Inova Fairfax Hospital
• Investigators: Principal Investigator: Peter S Pang, MD, Indiana University

Publications and helpful links

General Publications

• Pang PS, Russell FM, Ehrman R, Ferre R, Gargani L, Levy PD, Noble V, Lane KA, Li X, Collins SP. Lung Ultrasound-Guided Emergency Department Management of Acute Heart Failure (BLUSHED-AHF): A Randomized Controlled Pilot Trial. JACC Heart Fail. 2021 Sep;9(9):638-648. doi: 10.1016/j.jchf.2021.05.008. Epub 2021 Jul 7.
• Russell FM, Ehrman RR, Ferre R, Gargani L, Noble V, Rupp J, Collins SP, Hunter B, Lane KA, Levy P, Li X, O'Connor C, Pang PS. Design and rationale of the B-lines lung ultrasound guided emergency department management of acute heart failure (BLUSHED-AHF) pilot trial. Heart Lung. 2019 May-Jun;48(3):186-192. doi: 10.1016/j.hrtlng.2018.10.027. Epub 2018 Nov 15.

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2017
• Primary Completion (Actual): March 20, 2019
• Study Completion (Actual): June 20, 2019

Study Registration Dates

• First Submitted: April 19, 2017
• First Submitted That Met QC Criteria: April 26, 2017
• First Posted (Actual): May 2, 2017

Study Record Updates

• Last Update Posted (Actual): June 4, 2024
• Last Update Submitted That Met QC Criteria: June 1, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Heart Failure; Lung ultrasound; B-lines; Acute Heart Failure; Pulmonary Edema; Extra vascular lung water
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Respiratory Tract Diseases; Lung Diseases; Heart Failure; Pulmonary Edema; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Sodium Potassium Chloride Symporter Inhibitors; Vasodilator Agents
• Other Study ID Numbers: 1R34HL136986-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No