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Item 25 In-hospital Change in Lung Ultrasound Congestion Score Predicts Heart Failure Rehospitalization and Death: Implications for Clinical Trials(Cambridge University Press, 2023-04-24) Harrison, Nicholas Eric; Desai, Ankit; Pang, Peter; Emergency Medicine, School of MedicineOBJECTIVES/GOALS: Lung Ultrasound Congestion Score (LUS-CS) is a proposed measure for guiding treatment in acute heart failure (AHF). An emergency department (ED) pilot trial of LUS-guided diuresis showed reduced LUS-CS at 48 hours but no difference at hospital discharge or for clinical outcomes. We hypothesized total change in LUS-CS would predict adverse outcomes. METHODS/STUDY POPULATION: This was a post-hoc secondary analysis of the BLUSHED-AHF trial. BLUSHED-AHF was a pilot trial in which AHF patients were randomized to a LUS-guided diuresis strategy vs. usual care in the ED. The intervention was stopped after the ED course (i.e. during hospitalization). BLUSHED-AHF was designed for the intervention to target absolute values of LUS-CS over time, rather than change in LUS-CS from each patient’s baseline. We fit a cox regression model for a primary outcome of death or AHF rehospitalization, with total (ED to Hospital Discharge) change in LUS-CS as the primary predictor, adjusted for the Get-With-The-Guidelines heart failure risk score (GWTG). Survival curves were plotted, and hazard ratios calculated. RESULTS/ANTICIPATED RESULTS: 128 patients in BLUSHED-AHF were analyzed. Greater reduction in LUS-CS from ED to hospital discharge predicted event-free survival (HR = 0.74 for each 20 unit reduction in LUS-CS, 95%CI 0.56-0.99). This effect did not vary by hospitalization length or ED disposition. There was a significant interaction between change in LUS-CS and GWTG score. DISCUSSION/SIGNIFICANCE: LUS-CS total change, and not absolute values, predict adverse events in LUS-guided diuresis. Post-ED cessation of the intervention in BLUSHED-AHF may have precluded opportunity for clinical benefit. Future trials should run the entire hospital course, target change from baseline, and consider patient selection by AHF severity and initial LUS-CS.Item Design and Rationale of a Randomized Trial of a Care Transition Strategy in Patients With Acute Heart Failure Discharged From the Emergency Department: GUIDED-HF (Get With the Guidelines in Emergency Department Patients With Heart Failure).(American Heart Association, 2017-02) Fermann, Gregory J.; Levy, Phillip D.; Pang, Peter; Butler, Javed; Ayaz, S. Imran; Char, Douglas; Dunn, Pat; Jenkins, Cathy A.; Kampe, Christy; Khan, Yosef; Kumar, Vijaya A.; Lindenfeld, JoAnn; Liu, Dandan; Miller, Karen; Peacock, W. Frank; Rizk, Samaa; Robichaux, Chad; Rothman, Russell L.; Schrock, Jon; Singer, Adam; Sterling, Sarah A.; Storrow, Alan B.; Walsh, Cheryl; Wilburn, John; Collins, Sean P.; Emergency Medicine, School of MedicineGUIDED-HF (Get With the Guidelines in Emergency Department Patients With Heart Failure) is a multicenter randomized trial of a patient-centered transitional care intervention in patients with acute heart failure (AHF) who are discharged either directly from the emergency department (ED) or after a brief period of ED-based observation. To optimize care and reduce ED and hospital revisits, there has been significant emphasis on improving transitions at the time of hospital discharge for patients with HF. Such efforts have been almost exclusively directed at hospitalized patients; individuals with AHF who are discharged from the ED or ED-based observation are not included in these transitional care initiatives. Patients with AHF discharged directly from the ED or after a brief period of ED-based observation are randomly assigned to our transition GUIDED-HF strategy or standard ED discharge. Patients in the GUIDED arm receive a tailored discharge plan via the study team, based on their identified barriers to outpatient management and associated guideline-based interventions. This plan includes conducting a home visit soon after ED discharge combined with close outpatient follow-up and subsequent coaching calls to improve postdischarge care and avoid subsequent ED revisits and inpatient admissions. Up to 700 patients at 11 sites will be enrolled over 3 years of the study. GUIDED-HF will test a novel approach to AHF management strategy that includes tailored transitional care for patients discharged from the ED or ED-based observation. If successful, this program may significantly alter the current paradigm of AHF patient care.Item Hemodynamic profiles by non-invasive monitoring of cardiac index and vascular tone in acute heart failure patients in the emergency department: External validation and clinical outcomes(PLOS, 2022-03-31) Harrison, Nicholas Eric; Meram, Sarah; Li, Xiangrui; White, Morgan B.; Henry, Sarah; Gupta, Sushane; Zhu, Dongxiao; Pang, Peter; Levy, Phillip; Emergency Medicine, School of MedicineBackground: Non-invasive finger-cuff monitors measuring cardiac index and vascular tone (SVRI) classify emergency department (ED) patients with acute heart failure (AHF) into three otherwise-indistinguishable subgroups. Our goals were to validate these "hemodynamic profiles" in an external cohort and assess their association with clinical outcomes. Methods: AHF patients (n = 257) from five EDs were prospectively enrolled in the validation cohort (VC). Cardiac index and SVRI were measured with a ClearSight finger-cuff monitor (formerly NexFin, Edwards Lifesciences) as in a previous study (derivation cohort, DC, n = 127). A control cohort (CC, n = 127) of ED patients with sepsis was drawn from the same study as the DC. K-means cluster analysis previously derived two-dimensional (cardiac index and SVRI) hemodynamic profiles in the DC and CC (k = 3 profiles each). The VC was subgrouped de novo into three analogous profiles by unsupervised K-means consensus clustering. PERMANOVA tested whether VC profiles 1-3 differed from profiles 1-3 in the DC and CC, by multivariate group composition of cardiac index and vascular tone. Profiles in the VC were compared by a primary outcome of 90-day mortality and a 30-day ranked composite secondary outcome (death, mechanical cardiac support, intubation, new/emergent dialysis, coronary intervention/surgery) as time-to-event (survival analysis) and binary events (odds ratio, OR). Descriptive statistics were used to compare profiles by two validated risk scores for the primary outcome, and one validated score for the secondary outcome. Results: The VC had median age 60 years (interquartile range {49-67}), and was 45% (n = 116) female. Multivariate profile composition by cardiac index and vascular tone differed significantly between VC profiles 1-3 and CC profiles 1-3 (p = 0.001, R2 = 0.159). A difference was not detected between profiles in the VC vs. the DC (p = 0.59, R2 = 0.016). VC profile 3 had worse 90-day survival than profiles 1 or 2 (HR = 4.8, 95%CI 1.4-17.1). The ranked secondary outcome was more likely in profile 1 (OR = 10.0, 1.2-81.2) and profile 3 (12.8, 1.7-97.9) compared to profile 2. Diabetes prevalence and blood urea nitrogen were lower in the high-risk profile 3 (p<0.05). No significant differences between profiles were observed for other clinical variables or the 3 clinical risk scores. Conclusions: Hemodynamic profiles in ED patients with AHF, by non-invasive finger-cuff monitoring of cardiac index and vascular tone, were replicated de novo in an external cohort. Profiles showed significantly different risks of clinically-important adverse patient outcomes.Item The Prognostic Value of Improving Congestion on Lung Ultrasound During Treatment for Acute Heart Failure Differs Based on Patient Characteristics at Admission(Elsevier, 2024) Harrison, Nicholas E.; Ehrman, Robert; Collins, Sean; Desai, Ankit A.; Duggan, Nicole M.; Ferre, Rob; Gargani, Luna; Goldsmith, Andrew; Kapur, Tina; Lane, Katie; Levy, Phillip; Li, Xiaochun; Noble, Vicki E.; Russell, Frances M.; Pang, Peter; Emergency Medicine, School of MedicineBackground: Lung ultrasound congestion scoring (LUS-CS) is a congestion severity biomarker. The BLUSHED-AHF trial demonstrated feasibility for LUS-CS-guided therapy in acute heart failure (AHF). We investigated two questions: 1) does change (∆) in LUS-CS from emergency department (ED) to hospital-discharge predict patient outcomes, and 2) is the relationship between in-hospital decongestion and adverse events moderated by baseline risk-factors at admission? Methods: We performed a secondary analysis of 933 observations/128 patients from 5 hospitals in the BLUSHED-AHF trial receiving daily LUS. ∆LUS-CS from ED arrival to inpatient discharge (scale -160 to +160, where negative = improving congestion) was compared to a primary outcome of 30-day death/AHF-rehospitalization. Cox regression was used to adjust for mortality risk at admission [Get-With-The-Guidelines HF risk score (GWTG-RS)] and the discharge LUS-CS. An interaction between ∆LUS-CS and GWTG-RS was included, under the hypothesis that the association between decongestion intensity (by ∆LUS-CS) and adverse outcomes would be stronger in admitted patients with low-mortality risk but high baseline congestion. Results: Median age was 65 years, GWTG-RS 36, left ventricular ejection fraction 36 %, and ∆LUS-CS -20. In the multivariable analysis ∆LUS-CS was associated with event-free survival (HR = 0.61; 95 % CI: 0.38-0.97), while discharge LUS-CS (HR = 1.00; 95%CI: 0.54-1.84) did not add incremental prognostic value to ∆LUS-CS alone. As GWTG-RS rose, benefits of LUS-CS reduction attenuated (interaction p < 0.05). ∆LUS-CS and event-free survival were most strongly correlated in patients without tachycardia, tachypnea, hypotension, hyponatremia, uremia, advanced age, or history of myocardial infarction at ED/baseline, and those with low daily loop diuretic requirements. Conclusions: Reduction in ∆LUS-CS during AHF treatment was most associated with improved readmission-free survival in heavily congested patients with otherwise reassuring features at admission. ∆LUS-CS may be most useful as a measure to ensure adequate decongestion prior to discharge, to prevent early readmission, rather than modify survival.Item The Significance of Historical Troponin Elevation in Acute Heart Failure: Not as Reassuring as Previously Assumed(Wiley, 2023) Harrison, Nicholas E.; Ehrman, Robert; Pang, Peter; Armitage, Sarah; Abidov, Aiden; Perkins, Daniel; Peacock, Johnathon; Montelauro, Nicholas; Gupta, Sushane; Favot, Mark J.; Levy, Phillip; Emergency Medicine, School of MedicineBackground: Historical cardiac troponin (cTn) elevation is commonly interpreted as lessening the significance of current cTn elevations at presentation for acute heart failure (AHF). Evidence for this practice is lacking. Our objective was to determine the incremental prognostic significance of historical cTn elevation compared to cTn elevation and ischemic heart disease (IHD) history at presentation for AHF. Methods: A total of 341 AHF patients were prospectively enrolled at five sites. The composite primary outcome was death/cardiopulmonary resuscitation, mechanical cardiac support, intubation, new/emergent dialysis, and/or acute myocardial infarction (AMI)/percutaneous coronary intervention (PCI)/coronary artery bypass grafting (CABG) at 90 days. Secondary outcomes were 30-day AMI/PCI/CABG and in-hospital AMI. Logistic regression compared outcomes versus initial emergency department (ED) cTn, the most recent electronic medical record cTn, estimated glomerular filtration rate, age, left ventricular ejection fraction, and IHD history (positive, negative by prior coronary workup, or unknown/no prior workup). Results: Elevated cTn occurred in 163 (49%) patients, 80 (23%) experienced the primary outcome, and 29 had AMI (9%). cTn elevation at ED presentation, adjusted for historical cTn and other covariates, was associated with the primary outcome (adjusted odds ratio [aOR] 2.39, 95% confidence interval [CI] 1.30-4.38), 30-day AMI/PCI/CABG, and in-hospital AMI. Historical cTn elevation was associated with greater odds of the primary outcome when IHD history was unknown at ED presentation (aOR 5.27, 95% CI 1.24-21.40) and did not alter odds of the outcome with known positive (aOR 0.74, 95% CI 0.33-1.70) or negative IHD history (aOR 0.79, 95% CI 0.26-2.40). Nevertheless, patients with elevated ED cTn were more likely to be discharged if historical cTn was also elevated (78% vs. 32%, p = 0.025). Conclusions: Historical cTn elevation in AHF patients is a harbinger of worse outcomes for patients who have not had a prior IHD workup and should prompt evaluation for underlying ischemia rather than reassurance for discharge. With known IHD history, historical cTn elevation was neither reassuring nor detrimental, failing to add incremental prognostic value to current cTn elevation alone.Item Troponin is unrelated to outcomes in heart failure patients discharged from the emergency department(Wiley, 2022-04-09) Fermann, Gregory J.; Schrock, Jon W.; Levy, Phillip D.; Pang, Peter; Butler, Javed; Chang, Anna Marie; Char, Douglas; Diercks, Deborah; Han, Jin H.; Hiestand, Brian; Hogan, Chris; Jenkins, Cathy A.; Kampe, Christy; Khan, Yosef; Kumar, Vijaya A.; Lee, Sangil; Lindenfeld, JoAnn; Liu, Dandan; Miller, Karen F.; Peacock, W. Frank; Reilly, Carolyn M.; Robichaux, Chad; Rothman, Russell L.; Self, Wesley H.; Singer, Adam J.; Sterling, Sarah A.; Storrow, Alan B.; Stubblefield, William B.; Walsh, Cheryl; Wilburn, John; Collins, Sean P.; Emergency Medicine, School of MedicineBackground: Prior data has demonstrated increased mortality in hospitalized patients with acute heart failure (AHF) and troponin elevation. No data has specifically examined the prognostic significance of troponin elevation in patients with AHF discharged after emergency department (ED) management. Objective: Evaluate the relationship between troponin elevation and outcomes in patients with AHF who are treated and released from the ED. Methods: This was a secondary analysis of the Get with the Guidelines to Reduce Disparities in AHF Patients Discharged from the ED (GUIDED-HF) trial, a randomized, controlled trial of ED patients with AHF who were discharged. Patients with elevated conventional troponin not due to acute coronary syndrome (ACS) were included. Our primary outcome was a composite endpoint: time to 30-day cardiovascular death and/or heart failure-related events. Results: Of the 491 subjects included in the GUIDED-HF trial, 418 had troponin measured during the ED evaluation and 66 (16%) had troponin values above the 99th percentile. Median age was 63 years (interquartile range, 54-70), 62% (n = 261) were male, 63% (n = 265) were Black, and 16% (n = 67) experienced our primary outcome. There were no differences in our primary outcome between those with and without troponin elevation (12/66, 18.1% vs 55/352, 15.6%; P = 0.60). This effect was maintained regardless of assignment to usual care or the intervention arm. In multivariable regression analysis, there was no association between our primary outcome and elevated troponin (hazard ratio, 1.00; 95% confidence interval, 0.49-2.01, P = 0.994). Conclusion: If confirmed in a larger cohort, these findings may facilitate safe ED discharge for a group of patients with AHF without ACS when an elevated troponin is the primary reason for admission.Item The Vulnerable Phase of Heart Failure(Wolters Kluwer, 2018-07) Gracia, Ely; Singh, Prabhjot; Collins, Sean; Chioncel, Ovidiu; Pang, Peter; Butler, Javed; Emergency Medicine, IU School of Medicine