Browsing by Author "Chioncel, Ovidiu"
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Item Acute Heart Failure Assessment: The Role of Focused Emergency Cardiopulmonary Ultrasound in Identification and Early Management(Wiley, 2015-12) Ferre, Robinson M.; Chioncel, Ovidiu; Pang, Peter S.; Lang, Roberto M.; Gheorghiade, Mihai; Collins, Sean P.; Department of Emergency Medicine, IU School of MedicineItem Changes in Liver Function Tests, Congestion, and Prognosis After Acute Heart Failure: The STRONG-HF Trial(Elsevier, 2025) Myhre, Peder L.; Grupper, Avishay; Mebazaa, Alexandre; Davison, Beth; Edwards, Christopher; Takagi, Koji; Adamo, Marianna; Arrigo, Mattia; Barros, Marianela; Biegus, Jan; Celutkiene, Jelena; Čerlinskaitė-Bajorė, Kamilė; Chioncel, Ovidiu; Cohen-Solal, Alain; Damasceno, Albertino; Deniau, Benjamin; Diaz, Rafael; Filippatos, Gerasimos; Gayat, Etienne; Kimmoun, Antoine; Ter Maaten, Jozine M.; Metra, Marco; Novosadova, Maria; Pagnesi, Matteo; Pang, Peter S.; Ponikowski, Piotr; Saidu, Hadiza; Sliwa, Karen; Tomasoni, Daniela; Voors, Adriaan; Cotter, Gad; Lam, Carolyn S. P.; Emergency Medicine, School of MedicineBackground: Elevated alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (tBil) may reflect congestion and liver dysfunction in acute heart failure (AHF), while lower ALT also associates with sarcopenia. Objectives: The purpose of this study was to assess ALT, AST, and tBil levels in AHF patients during high-intensity care (HIC) vs usual care (UC) follow-up. Methods: ALT, AST, and tBil were measured 1 to 2 days predischarge in 1,062 AHF patients, and again after 90 days of either HIC or UC according to the STRONG-HF (Safety, Tolerability and efficacy of Rapid Optimization, helped by NT-proBNP testinG, of Heart Failure therapies) protocol. The primary endpoint was 180-day all-cause death or HF hospitalization. Results: Median (Q1-Q3) baseline ALT, AST, and tBil were 21 (15-32) U/L, 23 (17-32) U/L, and 14(10-21) umol/L, respectively. Patients with lower ALT had lower body mass index. Patients with lower ALT, but not tBil or AST, were more likely to have edema, elevated jugular venous pressure, and orthopnea, and use more diuretics prerandomization. A nonsignificant inverse association between ALT and the primary outcome (HR: 0.82 [95% CI: 0.66-1.01] per log-unit, P = 0.06) was observed. Greater reductions of ALT, AST, and tBil to 90 days were associated with greater improvement of edema, rales, NYHA functional class, and N-terminal pro-B-type natriuretic peptide. After 90 days, the HIC group had a greater reduction in AST and tBil than the UC group, while nonsignificant for ALT. The treatment effect of HIC over UC on the primary outcome was consistent across the baseline ALT, AST, and tBil range (all P interaction >0.10), but patients with lower ALT experienced greater health status improvement from HIC. Conclusions: Lower ALT was associated with lower body mass index and more congestion in AHF, supporting previous studies suggesting ALT as a sarcopenia marker. The beneficial effect of HIC on health status was greater in low baseline ALT patients.Item Improving Postdischarge Outcomes in Acute Heart Failure(Wolters Kluwer, 2018-07) Chioncel, Ovidiu; Collins, Sean P.; Ambrosy, Andrew P.; Pang, Peter S.; Antohi, Elena-Laura; Iliescu, Vlad Anton; Maggioni, Aldo P.; Butler, Javed; Mebazaa, Alexandre; Emergency Medicine, IU School of MedicineThe global burden that acute heart failure (AHF) carries has remained unchanged over the past several decades (1). European registries (2–5) showed that 1-year outcome rates remain unacceptably high (Table 1) and confirm that hospitalization for AHF represents a change in the natural history of the disease process(6). As patients hospitalized for HF have a bad prognosis, it is crucial to utilize hospitalization as an opportunity to: 1) assess the individual components of the cardiac substrate; 2) identify and treat comorbidities; 3) identify early, safe endpoints of therapy to facilitate timely hospital discharge and outpatient follow-up; and 4) implement and begin optimization guideline-directed medical therapies (GDMTs). As outcomes are influenced by many factors, many of which are incompletely understood, a systematic approach is proposed that should start with admission and continues through post-discharge (7).Item Mihai Gheorghiade, MD-Life and Concepts(Wolters Kluwer, 2018-07) Pang, Peter S.; Collins, Sean P.; Butler, Javed; Chioncel, Ovidiu; Emergency Medicine, IU School of MedicineHow do you capture an idea, shape it, and then bring it into the world? Of his many talents, this ability was a fundamental characteristic of Mihai Gheorghiade. A quick glance through PubMed confirms his prodigious output, likely to overwhelm any novice or even expert scholar. His contribution to heart failure, especially acute heart failure (AHF), is profound, He authored several major concepts in acute heart failure, disseminated further by his students. Most concepts remained indelibly linked to his name: Digoxin trials research(1–3), AHFS (acute heart failure syndromes) definition(4), hemodynamic congestion(5), hospitalized heart failure (HHF) (6), the vulnerable phase(7,8), neutral hemodynamic agents(9), registries(10–12) and pre-trial registries(13), the “6-axis model”(14) and then the “8-axis model”(15). His work shaped the field of AHF.Item Optimization of Evidence-Based Heart Failure Medications After an Acute Heart Failure Admission: A Secondary Analysis of the STRONG-HF Randomized Clinical Trial(American Medical Association, 2024) Cotter, Gad; Deniau, Benjamin; Davison, Beth; Edwards, Christopher; Adamo, Marianna; Arrigo, Mattia; Barros, Marianela; Biegus, Jan; Celutkiene, Jelena; Cerlinskaite-Bajore, Kamile; Chioncel, Ovidiu; Cohen-Solal, Alain; Damasceno, Albertino; Diaz, Rafael; Filippatos, Gerasimos; Gayat, Etienne; Kimmoun, Antoine; Lam, Carolyn S. P.; Metra, Marco; Novosadova, Maria; Pang, Peter S.; Pagnesi, Matteo; Ponikowski, Piotr; Saidu, Hadiza; Sliwa, Karen; Takagi, Koji; Ter Maaten, Jozine M.; Tomasoni, Daniela; Voors, Adriaan; Mebazaa, Alexandre; Emergency Medicine, School of MedicineImportance: The Safety, Tolerability, and Efficacy of Rapid Optimization, Helped by N-Terminal Pro-Brain Natriuretic Peptide Testing of Heart Failure Therapies (STRONG-HF) trial strived for rapid uptitration aiming to reach 100% optimal doses of guideline-directed medical therapy (GDMT) within 2 weeks after discharge from an acute heart failure (AHF) admission. Objective: To assess the association between degree of GDMT doses achieved in high-intensity care and outcomes. Design, setting, and participants: This was a post hoc secondary analysis of the STRONG-HF randomized clinical trial, conducted from May 2018 to September 2022. Included in the study were patients with AHF who were not treated with optimal doses of GDMT before and after discharge from an AHF admission. Data were analyzed from January to October 2023. Interventions: The mean percentage of the doses of 3 classes of HF medications (renin-angiotensin system inhibitors, β-blockers, and mineralocorticoid receptor antagonists) relative to their optimal doses was computed. Patients were classified into 3 dose categories: low (<50%), medium (≥50% to <90%), and high (≥90%). Dose and dose group were included as a time-dependent covariate in Cox regression models, which were used to test whether outcomes differed by dose. Main outcome measures: Post hoc secondary analyses of postdischarge 180-day HF readmission or death and 90-day change in quality of life. Results: A total of 515 patients (mean [SD] age, 62.7 [13.4] years; 311 male [60.4%]) assigned high-intensity care were included in this analysis. At 2 weeks, 39 patients (7.6%) achieved low doses, 254 patients (49.3%) achieved medium doses, and 222 patients (43.1%) achieved high doses. Patients with lower blood pressure and more congestion were less likely to be uptitrated to optimal GDMT doses at week 2. As a continuous time-dependent covariate, an increase of 10% in the average percentage optimal dose was associated with a reduction in 180-day HF readmission or all-cause death (primary end point: adjusted hazard ratio [aHR], 0.89; 95% CI, 0.81-0.98; P = .01) and a decrease in 180-day all-cause mortality (aHR, 0.84; 95% CI, 0.73-0.95; P = .007). Quality of life at 90 days, measured by the EQ-5D visual analog scale, improved more in patients treated with higher doses of GDMT (mean difference, 0.10; 95% CI, -4.88 to 5.07 and 3.13; 95% CI, -1.98 to 8.24 points in the medium- and high-dose groups relative to the low-dose group, respectively; P = .07). Adverse events to day 90 occurred less frequently in participants with HIC who were prescribed higher GDMT doses at week 2. Conclusions and relevance: Results of this post hoc analysis of the STRONG-HF randomized clinical trial show that, among patients randomly assigned to high-intensity care, achieving higher doses of HF GDMT 2 weeks after discharge was feasible and safe in most patients.Item Predictors of Post-discharge Mortality Among Patients Hospitalized for Acute Heart Failure(Radcliffe Cardiology, 2017-11) Chioncel, Ovidiu; Collins, Sean P.; Greene, Stephen J.; Pang, Peter S.; Ambrosy, Andrew P.; Antohi, Elena-Laura; Vaduganathan, Muthiah; Butler, Javed; Gheorghiade, Mihai; Emergency Medicine, School of MedicineAcute Heart Failure (AHF) is a " multi-event disease" and hospitalisation is a critical event in the clinical course of HF. Despite relatively rapid relief of symptoms, hospitalisation for AHF is followed by an increased risk of death and re-hospitalisation. In AHF, risk stratification from clinically available data is increasingly important in evaluating long-term prognosis. From the perspective of patients, information on the risk of mortality and re-hospitalisation would be helpful in providing patients with insight into their disease. From the perspective of care providers, it may facilitate management decisions, such as who needs to be admitted and to what level of care (i.e. floor, step-down, ICU). Furthermore, risk-stratification may help identify patients who need to be evaluated for advanced HF therapies (i.e. left-ventricle assistance device or transplant or palliative care), and patients who need early a post-discharge follow-up plan. Finally, risk stratification will allow for more robust efforts to identify among risk markers the true targets for therapies that may direct treatment strategies to selected high-risk patients. Further clinical research will be needed to evaluate if appropriate risk stratification of patients could improve clinical outcome and resources allocation.Item Rationale and Design of a Prospective, Multicenter, Observational Study Evaluating Iron Deficiency in Patients Hospitalized for Heart Failure (FERIC-RO)(Universidad Nacional de Trujillo, 2018-07-01) Antohi, Elena Laura; Chitoiu, Gabriel Tatu; Ambrosy, Andrew P.; Coman, Ioan M.; Vinereanu, Dragos; Collins, Sean P.; Sinescu, Crina; Mihaileanu, Serban; Pang, Peter S.; Butler, Javed; Chioncel, Ovidiu; Emergency Medicine, School of MedicineIntroduction: Several landmark studies, which enrolled heart failure (HF) patients who were ambulatory at the time of inclusion, identified iron deficiency (ID) as an important therapeutic target: intravenous iron administration with ferric carboxymaltose (FCM) improves morbidity, exercise capacity, and quality of life in patients with HF and reduced EF (HFrEF). However, there is still limited knowledge about ID prevalence during hospitalization for Worsening Chronic HF (WCHF) and about the relationship between ID during hospitalization and post-discharge outcomes. Although previous studies documented ID as an independent risk factor for poor outcomes in HFrEF, its prognostic significance in HF patients with EF>40% remains unclear. Method and Results: The FERIC-RO study is a prospective, multicenter, observational study with longitudinal follow up, conducted in 9 Romanian hospitals that will include 200 consecutive patients admitted for worsening HF. A comprehensive description of the Iron metabolism biomarkers will be performed on discharge and 1-month follow up. The primary endpoint is defined as the prevalence of ID on discharge and 1-month post-discharge, and the secondary endpoints include: all-cause re-hospitalization and all-cause-mortality at 1 and 3 months follow up, and quality of life on discharge and 1-month. Conclusions: FERIC-RO will provide new evidence about the prevalence and the predictors of ID in patients hospitalized for WCHF regardless of LVEF. Furthermore, the study will explore the relationship between in-hospital ID and post-discharge outcomes. The results of FERIC-RO will thus be highly relevant to the management of patients hospitalized for AHF.Item Safety, tolerability and efficacy of up-titration of guideline-directed medical therapies for acute heart failure (STRONG-HF): a multinational, open-label, randomised, trial(Elsevier, 2022-12-03) Mebazaa, Alexandre; Davison, Beth; Chioncel, Ovidiu; Cohen-Solal, Alain; Diaz, Rafael; Filippatos, Gerasimos; Metra, Marco; Ponikowski, Piotr; Sliwa, Karen; Voors, Adriaan A.; Edwards, Christopher; Novosadova, Maria; Takagi, Koji; Damasceno, Albertino; Saidu, Hadiza; Gayat, Etienne; Pang, Peter S.; Celutkiene, Jelena; Cotter, Gad; Emergency Medicine, School of MedicineBackground There is a paucity of evidence for dose and pace of up-titration of guideline-directed medical therapies after admission to hospital for acute heart failure. Methods In this multinational, open-label, randomised, parallel-group trial (STRONG-HF), patients aged 18–85 years admitted to hospital with acute heart failure, not treated with full doses of guideline-directed drug treatment, were recruited from 87 hospitals in 14 countries. Before discharge, eligible patients were randomly assigned (1:1), stratified by left ventricular ejection fraction (≤40% vs >40%) and country, with blocks of size 30 within strata and randomly ordered sub-blocks of 2, 4, and 6, to either usual care or high-intensity care. Usual care followed usual local practice, and high-intensity care involved the up-titration of treatments to 100% of recommended doses within 2 weeks of discharge and four scheduled outpatient visits over the 2 months after discharge that closely monitored clinical status, laboratory values, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations. The primary endpoint was 180-day readmission to hospital due to heart failure or all-cause death. Efficacy and safety were assessed in the intention-to-treat (ITT) population (ie, all patients validly randomly assigned to treatment). The primary endpoint was assessed in all patients enrolled at hospitals that followed up patients to day 180. Because of a protocol amendment to the primary endpoint, the results of patients enrolled on or before this amendment were down-weighted. This study is registered with ClinicalTrials.gov, NCT03412201, and is now complete. Findings Between May 10, 2018, and Sept 23, 2022, 1641 patients were screened and 1078 were successfully randomly assigned to high-intensity care (n=542) or usual care (n=536; ITT population). Mean age was 63·0 years (SD 13·6), 416 (39%) of 1078 patients were female, 662 (61%) were male, 832 (77%) were White or Caucasian, 230 (21%) were Black, 12 (1%) were other races, one (<1%) was Native American, and one (<1%) was Pacific Islander (two [<1%] had missing data on race). The study was stopped early per the data and safety monitoring board's recommendation because of greater than expected between-group differences. As of data cutoff (Oct 13, 2022), by day 90, a higher proportion of patients in the high-intensity care group had been up-titrated to full doses of prescribed drugs (renin-angiotensin blockers 278 [55%] of 505 vs 11 [2%] of 497; β blockers 249 [49%] vs 20 [4%]; and mineralocorticoid receptor antagonists 423 [84%] vs 231 [46%]). By day 90, blood pressure, pulse, New York Heart Association class, bodyweight, and NT-proBNP concentration had decreased more in the high-intensity care group than in the usual care group. Heart failure readmission or all-cause death up to day 180 occurred in 74 (15·2% down-weighted adjusted Kaplan-Meier estimate) of 506 patients in the high-intensity care group and 109 (23·3%) of 502 patients in the usual care group (adjusted risk difference 8·1% [95% CI 2·9–13·2]; p=0·0021; risk ratio 0·66 [95% CI 0·50–0·86]). More adverse events by 90 days occurred in the high-intensity care group (223 [41%] of 542) than in the usual care group (158 [29%] of 536) but similar incidences of serious adverse events (88 [16%] vs 92 [17%]) and fatal adverse events (25 [5%] vs 32 [6%]) were reported in each group. Interpretation An intensive treatment strategy of rapid up-titration of guideline-directed medication and close follow-up after an acute heart failure admission was readily accepted by patients because it reduced symptoms, improved quality of life, and reduced the risk of 180-day all-cause death or heart failure readmission compared with usual care.Item Socio‐economic status and the effect of guideline‐directed medical therapy in the STRONG‐HF study(Wiley, 2025) Damasceno, Albertino; Saidu, Hadiza; Cotter, Gad; Davison, Beth; Edwards, Christopher; Celutkiene, Jelena; Adamo, Marianna; Arrigo, Mattia; Barros, Marianela; Biegus, Jan; Čerlinskaitė-Bajorė, Kamilė; Chioncel, Ovidiu; Cohen-Solal, Alain; Deniau, Benjamin; Diaz, Rafael; Filippatos, Gerasimos; Gayat, Etienne; Kimmoun, Antoine; Lam, Carolyn S. P.; Metra, Marco; Novosadova, Maria; Pagnesi, Matteo; Pang, Peter S.; Ponikowski, Piotr; Ter Maaten, Jozine M.; Tomasoni, Daniela; Voors, Adriaan A.; Takagi, Koji; Mebazaa, Alexandre; Sliwa, Karen; Emergency Medicine, School of MedicineAims: Acute heart failure (AHF) impacts millions globally, with outcomes varying based on socio-economic status (SES). Methods: SES measured by annual household income, years of education and medical insurance coverage. Each patient's income and education level relative to the median or mean, respectively, in the country was calculated, and categorized into tertiles (0, 1 or 2 from lowest to highest). SES scores (0-5) were computed as the sum of these levels plus insurance coverage (0 = no or 1 = yes). Patients' baseline characteristics, outcomes (HF readmission, death and their composite) and the effect of high-intensity care (HIC) vs. usual care (UC) were examined by SES scores 0-2, 3 and 4-5. Results: Lower SES patients, who were younger, predominantly female, Black and non-European, had fewer comorbidities such as atrial fibrillation, diabetes and ischaemic heart disease and exhibited milder HF, indicated by a lower NYHA class, lower creatinine and higher cholesterol before discharge. Despite having milder HF and less comorbidities, after adjusting for baseline characteristics, patients with higher SES had numerically better outcomes, though differences were not statistically significant. 180-day hazard ratios (HRs) for HF readmission or death were 0.75 (95% CI 0.48-1.16) for SES scores of 3 and 0.85 (95% CI 0.58-1.23) for scores of 4-5, compared to 0-2. Higher SES patients had numerically better treatment effect from HIC, with HRs of 0.69 for SES 0-2, 0.72 for SES 3 and 0.50 for SES 4-5. Conclusions: In this post hoc analysis of the STRONG-HF study, lower SES was associated with milder acute HF but similar 180-day outcomes. Higher SES patients benefitted more from HIC.Item Therapeutic Advances in the Management of Acute Decompensated Heart Failure(Wolters Kluwer, 2019-03) Antohi, Elena-Laura; Ambrosy, Andrew P.; Collins, Sean P.; Ahmed, Ali; Iliescu, Vlad Anton; Cotter, Gad; Pang, Peter S.; Butler, Javed; Chioncel, Ovidiu; Emergency Medicine, School of MedicineBackground: Acute decompensated heart failure (ADHF) is the most common presenting phenotype of acute heart failure (AHF). The main goal of this article was to review the contemporary management strategies in these patients and to describe how future clinical trials may address unmet clinical needs. Areas of uncertainty: The current pathophysiologic understanding of AHF is incomplete. The guideline recommendations for the management of ADHF are based only on algorithms provided by expert consensus guided by blood pressure and/or clinical signs of congestion or hypoperfusion. The lack of adequately conducted trials to address the unmet need for evidence therapy in AHF has not yet been surpassed, and at this time, there is no evidence-based strategy for targeted decongestive therapy to improve outcomes. The precise time point for initiation of guideline-directed medical therapies (GDMTs), as respect to moment of decompensation, is also unknown. Data sources: The available data informing current management of patients with ADHF are based on randomized controlled trials, observational studies, and administrative databases. Therapeutic advances: A major step-forward in the management of ADHF patients is recognizing congestion, either clinical or hemodynamic, as a major trigger for heart failure (HF) hospitalization and most important target for therapy. However, a strategy based exclusively on congestion is not sufficient, and at present, comprehensive assessment during hospitalization of cardiac and noncardiovascular substrate with identification of potential therapeutic targets represents "the corner-stone" of ADHF management. In the last years, substantial data have emerged to support the continuation of GDMTs during hospitalization for HF decompensation. Recently, several clinical trials raised hypothesis of "moving to the left" concept that argues for very early implementation of GDMTs as potential strategy to improve outcomes. Conclusions: The management of ADHF is still based on expert consensus documents. Further research is required to identify novel therapeutic targets, to establish the precise time point to initiate GDMTs, and to identify patients at risk of recurrent hospitalization.