Browsing by Author "Levy, Phillip D."
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Item Biased ligand of the angiotensin II type 1 receptor in patients with acute heart failure: a randomized, double-blind, placebo-controlled, phase IIB, dose ranging trial (BLAST-AHF)(Oxford University Press, 2017-08-07) Pang, Peter S.; Butler, Javed; Collins, Sean P.; Cotter, Gad; Davison, Beth A.; Ezekowitz, Justin A.; Filippatos, Gerasimos; Levy, Phillip D.; Metra, Marco; Ponikowski, Piotr; Teerlink, John R.; Voors, Adriaan A.; Bharucha, David; Goin, Kathleen; Soergel, David G.; Felker, G. Michael; Emergency Medicine, School of MedicineAims: Currently, no acute heart failure (AHF) therapy definitively improves outcomes. Reducing morbidity and mortality from acute heart failure (AHF) remains an unmet need. TRV027 is a novel 'biased' ligand of the angiotensin II type 1 receptor (AT1R), selectively antagonizing the negative effects of angiotensin II, while preserving the potential pro-contractility effects of AT1R stimulation. BLAST-AHF was designed to determine the safety, efficacy, and optimal dose of TRV027 to advance into future studies. Methods and results: BLAST-AHF was a multi-centre, international, randomized, double-blind, placebo-controlled, parallel group, phase IIb dose-ranging study, enrolling patients with AHF into 4 groups: placebo, 1, 5, or 25 mg/h of TRV027. Treatment was by IV infusion for 48-96 h. The primary composite endpoint was comprised of the following: (i) time from baseline to death through day 30, (ii) time from baseline to heart failure re-hospitalization through day 30, (iii) the first assessment time point following worsening heart failure through day 5, (iv) change in dyspnea visual analogue scale (VAS) score calculated as the area under the curve (AUC) representing the change from baseline over time from baseline through day 5, and (v) length of initial hospital stay (in days) from baseline. Analyses were by modified intention-to-treat. Overall, 621 patients were enrolled. After 254 patients, a pre-specified interim analysis resulted in several protocol changes, including a lower blood pressure inclusion criterion as well as a new allocation scheme of 2:1:2:1, overweighting both placebo, and the 5 mg/h dose. TRV027 did not confer any benefit over placebo at any dose with regards to the primary composite endpoint or any of the individual components. There were no significant safety issues with TRV027. Conclusion: In this phase IIb dose-ranging AHF study, TRV027 did not improve clinical status through 30-day follow-up compared with placebo.Item Clinical and Research Considerations for Patients with Hypertensive Acute Heart Failure(Elsevier, 2016-08) Collins, Sean P.; Levy, Phillip D.; Martindale, Jennifer L.; Dunlap, Mark E.; Storrow, Alan B.; Pang, Peter S.; Sawyer, Douglas B.; Fermann, Gregory J.; Lenihan, Daniel J.; Peacock, W. Frank; Albert, Nancy M.; Hollander, Judd E.; Lindenfeld, JoAnn M.; Teerlink, John R.; Felker, G. Michael; Fonarow, Gregg C.; Butler, Javed; Department of Emergency Medicine, IU School of MedicineManagement approaches for patients in the emergency department (ED) who present with acute heart failure (AHF) have largely focused on intravenous diuretics. Yet, the primary pathophysiologic derangement underlying AHF in many patients is not solely volume overload. Patients with hypertensive AHF (H-AHF) represent a clinical phenotype with distinct pathophysiologic mechanisms that result in elevated ventricular filling pressures. To optimize treatment response and minimize adverse events in this subgroup, we propose that clinical management be tailored to a conceptual model of disease based on these mechanisms. This consensus statement reviews the relevant pathophysiology, clinical characteristics, approach to therapy, and considerations for clinical trials in ED patients with H-AHF.Item Delirium and its association with short-term outcomes in younger and older patients with acute heart failure(Public Library of Science, 2022-07-26) Han, Jin H.; McNaughton, Candace D.; Stubblefield, William B.; Pang, Peter S.; Levy, Phillip D.; Miller, Karen F.; Meram, Sarah; Cole, Mette Lind; Jenkins, Cathy A.; Paz, Hadassah H.; Moser, Kelly M.; Storrow, Alan B.; Collins, Sean P.; Emergency Medicine Research and Outcomes Consortium Investigators; Emergency Medicine, School of MedicineYounger patients (18 to 65 years old) are often excluded from delirium outcome studies. We sought to determine if delirium was associated with short-term adverse outcomes in a diverse cohort of younger and older patients with acute heart failure (AHF). We conducted a multi-center prospective cohort study that included adult emergency department patients with confirmed AHF. Delirium was ascertained using the Brief Confusion Assessment Method (bCAM). The primary outcome was a composite outcome of 30-day all-cause death, 30-day all-cause rehospitalization, and prolonged index hospital length of stay. Multivariable logistic regression was performed, adjusting for demographics, cognitive impairment without delirium, and HF risk factors. Older age (≥ 65 years old)*delirium interaction was also incorporated into the model. Odds ratios (OR) with their 95% confidence intervals (95%CI) were reported. A total of 1044 patients with AHF were enrolled; 617 AHF patients were < 65 years old and 427 AHF patients were ≥ 65 years old, and 47 (7.6%) and 40 (9.4%) patients were delirious at enrollment, respectively. Delirium was significantly associated with the composite outcome (adjusted OR = 1.64, 95%CI: 1.02 to 2.64). The older age*delirium interaction p-value was 0.47. In conclusion, delirium was common in both younger and older patients with AHF and was associated with poorer short-term outcomes in both cohorts. Younger patients with acute heart failure should be included in future delirium outcome studies.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 Design and rationale of a randomized trial: Using short stay units instead of routine admission to improve patient centered health outcomes for acute heart failure patients (SSU-AHF)(Elsevier, 2018-09) Fish-Trotter, Hannah; Collins, Sean; Danagoulian, Shooshan; Hunter, Benton; Li, Xiaochun; Levy, Phillip D.; Messina, Frank; Pressler, Susan; Pang, Peter S.; School of NursingNearly 85% of acute heart failure (AHF) patients who present to the emergency department (ED) with acute heart failure are hospitalized. Once hospitalized, 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 long-term outcomes. ED treatment is largely the same today as 40 years ago. Admitting patients who could have avoided hospitalization may contribute to adverse outcomes. Hospitalization is not benign; patients enter a vulnerable phase post-discharge, at increased risk for morbidity and mortality. When hospitalization is able to be shortened or avoid completely, certain risks can be mitigated, including risk of medication errors, in-hospital falls, delirium, nosocomial infections, and other iatrogenic complications. Additionally, patients would prefer to be home, not hospitalized. Furthermore, hospitalization and re-hospitalization for AHF predominantly affects patients of lower socioeconomic status (SES). Avoiding hospitalization in patients who do not require admission may improve outcomes and quality of life, while reducing costs. Short stay unit (SSU: <24 h, also referred to as an ‘observation unit’) management of AHF may be effective for lower risk patients. However, to date there have only been small studies or retrospective analyses on the SSU management for AHF patients. In addition, SSU management has been considered ‘cheating’ for hospitals trying to avoid 30-day readmission penalties, as SSUs or observation units do not count as an admission. However, more recent analyses demonstrate differential use of observation status has not led to decreases in re-admission, suggesting this concern may be misplaced. Thus, we propose a robust clinical effectiveness trial to demonstrate the effectiveness of this patient-centered strategy.Item Design and rationale of the high-sensitivity Troponin T Rules Out Acute Cardiac Insufficiency Trial(Dove Press, 2017-05-18) Hunter, Benton R.; Collins, Sean P.; Fermann, Gregory J.; Levy, Phillip D.; Shen, Changyu; Ayaz, Syed Imran; Cole, Mette L.; Miller, Karen F.; Soliman, Adam A.; Pang, Peter S.; Emergency Medicine, School of MedicineBACKGROUND: Acute heart failure (AHF) is a common presentation in the Emergency Department (ED), and most patients are admitted to the hospital. Identification of patients with AHF who have a low risk of adverse events and are suitable for discharge from the ED is difficult, and an objective tool would be useful. METHODS: The highly sensitive Troponin T Rules Out Acute Cardiac Insufficiency Trial (TACIT) will enroll ED patients being treated for AHF. Patients will undergo standard ED evaluation and treatment. High-sensitivity troponin T (hsTnT) will be drawn at the time of enrollment and 3 hours after the initial draw. The initial hsTnT draw will be no more than 3 hours after initiation of therapy for AHF (vasodilator, loop diuretic, noninvasive ventilation). Treating clinicians will be blinded to hsTnT results. We will assess whether hsTnT, as a single measurement or in series, can accurately predict patients at low risk of short-term adverse events. CONCLUSION: TACIT will explore the value of hsTnT measurements in isolation, or in combination with other markers of disease severity, for the identification of ED patients with AHF who are at low risk of short-term adverse events.Item Early echocardiographic assessment of cardiac function may be prognostically informative in unresuscitated patients with sepsis: A prospective observational study(Public Library of Science, 2022-07-08) Ehrman, Robert R.; Favot, Mark J.; Harrison, Nicholas E.; Khait, Lyudmila; Ottenhoff, Jakob E.; Welch, Robert D.; Levy, Phillip D.; Sherwin, Robert L.; Emergency Medicine, School of MedicinePurpose: The goal of this study was to explore the association cardiac function at Emergency Department (ED) presentation prior to the initiation of resuscitation, and its change at 3-hours, with adverse outcomes in patients with sepsis. Methods: This was a prospective observational study of patients presenting to an urban ED with suspected sepsis. Patients had a point-of-care echocardiogram performed prior to initiation of resuscitation and again 3 hours later. Left-ventricular (LV) parameters recorded included e', and E/e', and ejection fraction (EF); right-ventricular (RV) function was evaluated using tricuspid annular plane systolic excursion (TAPSE). Logistic and generalized linear regression were used to assess the association of echocardiographic parameters and ≥ 2-point increase in SOFA score at 24 hours (primary outcome) and 24-hours SOFA score and in-hospital mortality (secondary outcomes). Results: For ΔSOFA ≥ 2 and 24-hour SOFA score, declining LVEF was associated with better outcomes in patients with greater baseline SOFA scores, but worse outcomes in patients with lower baseline scores. A similar relationship was found for ΔTAPSE at 3 hours. Reduced LVEF at presentation was associated with increased mortality after adjusting for ED SOFA score (odds-ratio (OR) 0.76 (CI 0.60-0.96). No relationship between diastolic parameters and outcomes was found. IVF administration was similar across ΔLVEF/TAPSE sub-groups. Conclusions: Our results suggest that early change in LV and RV systolic function are independently prognostic of sepsis illness severity at 24-hours. Further study is needed to determine if this information can be used to guide treatment and improve outcomes.Item Effect of a Self-care Intervention on 90-Day Outcomes in Patients With Acute Heart Failure Discharged From the Emergency Department: A Randomized Clinical Trial(American Medical Association, 2021) Collins, Sean P.; Liu, Dandan; Jenkins, Cathy A.; Storrow, Alan B.; Levy, Phillip D.; Pang, Peter S.; Chang, Anna Marie; Char, Douglas; Diercks, Deborah J.; Fermann, Gregory J.; Han, Jin H.; Hiestand, Brian; Hogan, Christopher; Kampe, Christina J.; Khan, Yosef; Lee, Sangil; Lindenfeld, JoAnn; Martindale, Jennifer; McNaughton, Candace D.; Miller, Karen F.; Miller-Reilly, Carolyn; Moser, Kelly; Peacock, W. Frank; Robichaux, Chad; Rothman, Russell; Schrock, Jon; Self, Wesley H.; Singer, Adam J.; Sterling, Sarah A.; Ward, Michael J.; Walsh, Cheryl; Butler, Javed; Emergency Medicine, School of MedicineImportance: Up to 20% of patients who present to the emergency department (ED) with acute heart failure (AHF) are discharged without hospitalization. Compared with rates in hospitalized patients, readmission and mortality are worse for ED patients. Objective: To assess the impact of a self-care intervention on 90-day outcomes in patients with AHF who are discharged from the ED. Design, setting, and participants: Get With the Guidelines in Emergency Department Patients With Heart Failure was an unblinded, parallel-group, multicenter randomized trial. Patients were randomized 1:1 to usual care vs a tailored self-care intervention. Patients with AHF discharged after ED-based management at 15 geographically diverse EDs were included. The trial was conducted from October 28, 2015, to September 5, 2019. Interventions: Home visit within 7 days of discharge and twice-monthly telephone-based self-care coaching for 3 months. Main outcomes and measures: The primary outcome was a global rank of cardiovascular death, HF-related events (unscheduled clinic visit due to HF, ED revisit, or hospitalization), and changes in the Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) summary score (SS) at 90 days. Key secondary outcomes included the global rank outcome at 30 days and changes in the KCCQ-12 SS score at 30 and 90 days. Intention-to-treat analysis was performed for the primary, secondary, and safety outcomes. Per-protocol analysis was conducted including patients who completed a home visit and had scheduled outpatient follow-up in the intervention arm. Results: Owing to slow enrollment, 479 of a planned 700 patients were randomized: 235 to the intervention arm and 244 to the usual care arm. The median age was 63.0 years (interquartile range, 54.7-70.2), 302 patients (63%) were African American, 305 patients (64%) were men, and 178 patients (37%) had a previous ejection fraction greater than 50%. There was no significant difference in the primary outcome between patients in the intervention vs usual care arm (hazard ratio [HR], 0.89; 95% CI, 0.73-1.10; P = .28). At day 30, patients in the intervention arm had significantly better global rank (HR, 0.80; 95% CI, 0.64-0.99; P = .04) and a 5.5-point higher KCCQ-12 SS (95% CI, 1.3-9.7; P = .01), while at day 90, the KCCQ-12 SS was 2.7 points higher (95% CI, -1.9 to 7.2; P = .25). Conclusions and relevance: The self-care intervention did not improve the primary global rank outcome at 90 days in this trial. However, benefit was observed in the global rank and KCCQ-12 SS at 30 days, suggesting that an early benefit of a tailored self-care program initiated at an ED visit for AHF was not sustained through 90 days.Item Feasibility of Serial 6-min Walk Tests in Patients with Acute Heart Failure(MDPI, 2017-09-11) Collins, Sean P.; Thorn, Michael; Nowak, Richard M.; Levy, Phillip D.; Fermann, Gregory J.; Hiestand, Brian C.; Cowart, Tillman Douglas; Venuti, Robert P.; Hiatt, William R.; Foo, ShiYin; Pang, Peter S.; Emergency Medicine, School of MedicineBackground: Functional status assessment is common in many cardiovascular diseases but it has undergone limited study in the setting of acute heart failure (AHF). Accordingly, we performed a pilot study of the feasibility of the six-minute walk test (6MWT) at the emergency department (ED) presentation and through the hospitalization in patients with AHF. Methods and Results: From November 2014 to February 2015, we conducted a multicenter, observational study of ED patients, aged 18–85 years, whose primary ED admission diagnosis was AHF. Other criteria for enrollment included a left ventricular ejection fraction ≤40%, systolic blood pressure between 90 and 170 mmHg, and verbal confirmation that the patient was able to walk >30 m at the baseline, prior to ED presentation. Study teams were uniformly trained to administer a 6MWT. Patients underwent a baseline 6MWT within 24 h of ED presentation (Day 1) and follow-up 6MWTs at 24 (Day 2), 48 (Day 3), and 120 h (Day 5). A total of 46 patients (65.2% male, 73.9% African American) had a day one mean walk distance of 137.3 ± 78 m, day 2 of 170.9 ± 100 m, and day 3 of 180.8 ± 98 m. The 6MWT demonstrated good reproducibility, as the distance walked on the first 6MWT on Day 3 was similar to the distance on the repeated 6MWT the same day. Conclusions: Our pilot study demonstrates the feasibility of the 6MWT as a functional status endpoint in AHF patients. A larger study in a more demographically diverse cohort of patients is necessary to confirm its utility and association with 30-day heart failure (HF) events.Item Improvement in Kansas City Cardiomyopathy Questionnaire Scores After a Self-Care Intervention in Patients With Acute Heart Failure Discharged From the Emergency Department(American Heart Association, 2021) Stubblefield, William B.; Jenkins, Cathy A.; Liu, Dandan; Storrow, Alan B.; Spertus, John A.; Pang, Peter S.; Levy, Phillip D.; Butler, Javed; Chang, Anna Marie; Char, Douglas; Diercks, Deborah B.; Fermann, Gregory J.; Han, Jin H.; Hiestand, Brian C.; Hogan, Christopher J.; Khan, Yosef; Lee, Sangil; Lindenfeld, JoAnn M.; McNaughton, Candace D.; Miller, Karen; Peacock, W. Frank; Schrock, Jon W.; Self, Wesley H.; Singer, Adam J.; Sterling, Sarah A.; Collins, Sean P.; Emergency Medicine, School of MedicineBackground: We conducted a secondary analysis of changes in the Kansas City Cardiomyopathy Questionnaire (KCCQ)-12 over 30 days in a randomized trial of self-care coaching versus structured usual care in patients with acute heart failure who were discharged from the emergency department. Methods: Patients in 15 emergency departments completed the KCCQ-12 at emergency department discharge and at 30 days. We compared change in KCCQ-12 scores between the intervention and usual care arms, adjusted for enrollment KCCQ-12 and demographic characteristics. We used linear regression to describe changes in KCCQ-12 summary scores and logistic regression to characterize clinically meaningful KCCQ-12 subdomain changes at 30 days. Results: There were 350 patients with both enrollment and 30-day KCCQ summary scores available; 166 allocated to usual care and 184 to the intervention arm. Median age was 64 years (interquartile range, 55-70), 37% were female participants, 63% were Black, median KCCQ-12 summary score at enrollment was 47 (interquartile range, 33-64). Self-care coaching resulted in significantly greater improvement in health status compared with structured usual care (5.4-point greater improvement, 95% CI, 1.12-9.68; P=0.01). Improvements in health status in the intervention arm were driven by improvements within the symptom frequency (adjusted odds ratio, 1.62 [95% CI, 1.01-2.59]) and quality of life (adjusted odds ratio, 2.39 [95% CI, 1.46-3.90]) subdomains. Conclusions: In this secondary analysis, patients with acute heart failure who received a tailored, self-care intervention after emergency department discharge had clinically significant improvements in health status at 30 days compared with structured usual care largely due to improvements within the symptom frequency and quality of life subdomains of the KCCQ-12.