Impact of Hypoactive and Mixed Delirium on Short-Term Survival in Older Adults Hospitalised for Acute Heart Failure: A Prospective Study in an Acute Geriatric Unit

Impact of Hypoactive and Mixed Delirium on Short-Term Survival in Older Adults Hospitalised for Acute Heart Failure: A Prospective Study in an Acute Geriatric Unit | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Impact of Hypoactive and Mixed Delirium on Short-Term Survival in Older Adults Hospitalised for Acute Heart Failure: A Prospective Study in an Acute Geriatric Unit Alberto Finazzi, Chukwuma Okoye, Elena Pinardi, Alice Margherita Ornago, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7668204/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 6 You are reading this latest preprint version Abstract PURPOSE Delirium is a common complication in older adults hospitalised for acute heart failure (AHF), but its incidence, subtypes, and short-term outcomes remain poorly characterised in the very old population. This study aimed to determine the prevalence and incidence of delirium in patients admitted to an acute geriatric unit (AGU) with AHF, to describe its subtypes, and to assess their impact on 90-day post-discharge survival. METHODS This prospective observational study included older adults hospitalised for AHF in an AGU between April 2022 and November 2024. Delirium was assessed using the 4AT and DSM-5 criteria and categorised as prevalent (on admission) or incident (during hospitalisation). Psychomotor delirium subtypes were classified as hyperactive, hypoactive, or mixed. Sociodemographic, clinical, and follow-up data were collected. Ninety-day survival was evaluated using Kaplan-Meier curves and Cox regression models. RESULTS Among 399 patients (median age 87.4 years, 52% female), 132 (33%) experienced delirium, with 13.8% classified as prevalent and 19.2% as incident cases. Among those with delirium, 48% presented with the hyperactive, 31% with hypoactive, and 21% with the mixed subtype. In multivariable regression analysis, adjusted for relevant covariates, the hypoactive (adjusted HR 2.03, 95% CI 1.13–3.64) and mixed (adjusted HR 2.28, 95% CI 1.18–4.43) subtypes –but not hyperactive–were independently associated with an increased risk of death. CONCLUSIONS Delirium is common in very old patients hospitalised for AHF. The hypoactive and mixed subtypes are independently associated with poor 90-day post-discharge survival, highlighting the importance of their active identification and management. Acute Heart Failure Delirium Subtypes Older Adults Mortality Figures Figure 1 Figure 2 Key summary points Aim: to determine the prevalence and incidence of delirium subtypes in older adults with AHF and evaluate their impact on 90-day survival. Findings: among 399 patients (median age 87.4 years), delirium occurred in 33%, with 48% hyperactive, 31% hypoactive, and 21% mixed. Only hypoactive and mixed subtypes were independently associated with increased 90-day mortality. Message: early recognition of delirium psychomotor subtypes may help risk stratification and tailored care. INTRODUCTION Delirium is a neuropsychiatric syndrome characterised by acute dysfunction in attention and awareness, typically with a fluctuating course, and triggered by acute medical illness[ 1 ]. It is common among hospitalised patients and is associated with multiple adverse outcomes[ 2 – 7 ]. Clinically, delirium can be categorised into three psychomotor subtypes: hyperactive, hypoactive, and mixed. Hyperactive delirium is characterized by increased motor activity, mood lability, agitation, and/or refusal to cooperate with medical care; hypoactive delirium presents with reduced activity and speech, sluggishness, and lethargy approaching stupor. Mixed delirium involves alternating features of both[ 1 ]. Previous studies suggest that delirium affects up to one in four adults hospitalised with acute heart failure (AHF) [ 8 – 10 ], with significant implications for both survival and discharge outcomes [ 11 ]. However, most evidence comes from relatively younger populations, while patients over 80 years — paradoxically, the fastest-growing group hospitalised for AHF [ 12 – 14 ] — remain underrepresented. In this older cohort, existing studies offer limited data on the prevalence, incidence, and motor subtypes of delirium, and their prognostic relevance remains unclear[ 10 , 15 ]. In particular, the association between delirium subtypes and mortality in AHF remains poorly understood. To address this gap, we investigated delirium in a cohort of patients aged 80 or older admitted to an acute geriatric unit (AGU) for AHF, focusing on its prevalence, incidence, and the impact of psychomotor subtypes on 90-day post-discharge survival. METHODS Study design, data collection, and ethics statement This is a prospective observational study conducted on older adults admitted to the AGU of a tertiary referral hospital in Northern Italy. Patients were enrolled consecutively from April 2022 to November 2024. All patients who provided consent either directly or through a next of kin were enrolled in the study. Data collected included biological, sociodemographic, and social information, as well as details regarding hospitalisation and 12-month mortality outcomes. We included patients discharged alive following hospitalisation for AHF. The data were collected using an electronic case report form (eCRF) by trained personnel using Research Electronic Data Capture (REDCap)[ 16 ]. The study was approved by the Lombardy Regional Ethics Committee (Deliberation No. 1205, December 14, 2022) and conducted in accordance with the principles of the Declaration of Helsinki. The results are reported in compliance with the STROBE statement[ 17 ]. Baseline clinical variables AHF was defined as the rapid or gradual onset of symptoms and/or signs of heart failure requiring unplanned hospital admission[ 12 ]. When available, the left ventricular ejection fraction (LVEF) measured within the prior year was used to classify HF subtype, in accordance with international guidelines[ 12 ]. Routine blood tests were performed within 48 hours of admission. NT-proBNP measurement was left to the discretion of the attending physician, reflecting the real-world nature of the study. Upon admission, National Early Warning Score 2 (NEWS-2) parameters—including respiratory rate, oxygen saturation (with or without hypercapnia), oxygen supplementation, blood pressure, heart rate, consciousness level, and temperature—were assessed[ 18 ]. A routine comprehensive geriatric assessment (CGA) was also conducted, including sociodemographic data, Charlson Comorbidity Index (CCI)[ 19 ], functional status (Activities of Daily Living [ADL] and Instrumental Activities of Daily Living [IADL])[ 20 ], nutritional status (albumin levels), and prior history of dementia, identified through medical records or previous prescriptions for acetylcholinesterase inhibitors or memantine. The Clinical Frailty Scale (CFS) was scored by a senior geriatrician, according to a standardized classification tree[ 21 ]. Delirium Delirium was assessed on admission and daily during hospitalisation by a senior geriatrician using the 4AT [ 22 ]. The 4AT is a validated screening tool for the detection of delirium, with scores ≥ 4 indicating possible delirium. In such cases, the diagnosis was confirmed according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM–5)[ 1 ]. Delirium was classified as prevalent if present at admission and as incident if it developed during the hospital stay. Psychomotor subtypes were identified using DSM–5 criteria and classified as hyperactive, hypoactive, or mixed[ 1 ]. All patients received an individualised delirium prevention and management plan shortly after admission, including medication review and interventions addressing common risk factors. In patients with dementia, non-pharmacological strategies were implemented through referral to occupational therapy, in accordance with established guidelines[ 23 ]. When pharmacological treatment was required, trazodone or haloperidol was preferred, while benzodiazepines and drugs with high anticholinergic burden were avoided. If severe agitation posed a safety risk and was unresponsive to other measures, physical restraints (soft devices or straps) were used as a last resort, following international guidelines[ 24 ]. Their use required informed consent from patients or next of kin, obtained at admission, and was subject to regular and close multidisciplinary review. Follow-up and outcome variable Follow-up data were retrieved by a trained data manager via the Lombardy Regional Socio-Healthcare Information System portal. For each patient, the date of hospital discharge and, where applicable, the date of death were recorded. These variables were used to derive 90-day post-discharge survival, expressed both as a time-to-event variable (days from discharge to death, right-censored at 90 days) and as a binary variable indicating survival status at 90 days post-discharge (alive or deceased). Statistical analysis Socio-demographic and clinical characteristics were analysed using descriptive statistics. Categorical variables were summarised as absolute frequencies and percentages, while continuous variables were expressed as medians with interquartile ranges (IQRs). Group comparisons were performed using the Kruskal–Wallis test for continuous variables and Pearson’s chi-square test for categorical variables. Post-hoc pairwise comparisons were conducted using Dunn’s test and pairwise chi-square tests, both with Bonferroni correction. Overall survival (OS) was defined as the time from hospital discharge to death from any cause. Patients who were alive 90 days after discharge were censored at that time point. OS was estimated using the Kaplan-Meier method, with survival curves compared between groups using the log-rank test. Univariable and multivariable Cox proportional-hazards regression models were fitted to evaluate the association between socio-demographic, clinical characteristics, and OS. Selection of explanatory variables was informed by clinical relevance and considering previous literature[ 10 ]. A modified version of the NEWS2 score, excluding consciousness from the global score, was employed to avoid collinearity with delirium. All statistical analyses were conducted using R software, version 4.5.1 (2025-06-13)[ 25 ]. RESULTS Among the 2,212 patients admitted to the AGU during the study period, 444 (20.1%) were diagnosed with AHF at admission ( Supplementary Fig. 1 ). Of these, 45 patients (10.1%) died during hospitalisation, resulting in 399 patients eligible for final analysis (median age 87 years [IQR, 83.9 − 90.6]; 52% female). Delirium was diagnosed in 132 patients (33.1%), of whom 55 (13.8%) had prevalent and 77 (19.2%) incident delirium. The hyperactive subtype was the most frequent (48%, 64/132), followed by hypoactive (31%, 41/132) and mixed (21%, 27/132) subtypes. The distribution of psychomotor subtypes is shown in Supplementary Fig. 2 . Table 1 shows the characteristics of the overall study population, stratified by delirium status. No significant differences in age or CCI were observed between patients with and without delirium. The prevalence of ischemic heart disease, atrial fibrillation, chronic obstructive pulmonary disease (COPD), diabetes, and chronic kidney disease was comparable between groups. Heart failure with preserved ejection fraction (HFpEF) was the predominant phenotype in both groups, accounting for over half of cases with available LVEF data. Table 1 Main characteristics of the overall sample and according to delirium occurrence during hospitalisation. Overall (N = 399) Delirium (N = 132) No delirium (N = 267) p-value Age, median [IQR] 87.4 [83.9, 90.6] 88.2 [83.6, 91.3] 87.4 [84.0, 90.3] 0.5 Female, n (%) 207 (52) 64 (48) 143 (54) 0.4 ADL, median [IQR] 4.0 [1.0, 6.0] 3.0 [1.0, 5.0] 5.0 [2.0, 6.0] < 0.001 IADL, median [IQR] 2.0 [0.0, 3.0] 1.0 [0.0, 2.0] 2.0 [1.0, 4.0] < 0.001 CFS, median [IQR] 6.0 [5.0, 7.0] 7.0 [6.0, 7.0] 6.0 [5.0, 7.0] < 0.001 Albumin (g/L), median [IQR] 34.0 [30.0, 37.0] 33.5 [30.5, 37.0] 34.0 [30.0, 36.0] 0.6 Dementia, n (%) 117 (29) 62 (47) 55 (21) < 0.001 CCI, median [IQR] 6.0 [5.0, 8.0] 6.0 [5.0, 8.0] 6.0 [5.0, 8.0] 0.9 Ischemic heart disease, n (%) 95 (24) 27 (20) 68 (26) 0.3 Atrial fibrillation, n (%) 192 (48) 59 (45) 135 (50) 0.4 COPD, n (%) 81 (20) 28 (21) 53 (20) 0.9 Diabetes mellitus 119 (30) 37 (28) 82 (31) 0.6 CKD, n (%) 155 (39) 42 (32) 117 (42) 0.062 Type of HF 0.4 HFmrEF, n (%) 52 (13) 22 (17) 30 (11) HFpEF, n (%) 122 (31) 36 (27) 86 (32) HFrEF, n (%) 41 (10) 13 (9.8) 28 (10) Unknown, n (%) 184 (46) 61 (46) 123 (46) NT-proBNP† (pg/mL), median [IQR] 6,341.0 [3,088.0, 13,276.0] 6,558.0 [2,732.0, 12,511.0] 6,088.0 [3,150.0, 13,364.0] 0.9 LOS, median [IQR] 12.0 [9.0, 16.0] 13.0 [10.0, 18.0] 12.0 [9.0, 15.0] 0.009 Discharged home, n (%) 330 (83%) 102 (77%) 228 (86%) 0.049 90-days mortality, n (%) 99 (25) 47 (36) 52 (19) < 0.001 Abbreviations: ADL, activities of daily living; CCI, Charlson comorbidity index; CKD, chronic kidney disease; CFS, clinical frailty scale; COPD, chronic obstructive pulmonary disease; IADL, instrumental activities of daily living; HF, heart failure; HFrEF, with reduced Ejection Fraction; HFmrEF, with mildly reduced ejection fraction; HFpEF, with preserved ejection fraction; LOS, length of stay. †Data available for 233 patients (58% of the total cohort). Patients with delirium showed greater functional impairment in ADL (3.0 [1.0, 5.0] vs. 5.0 [2.0, 6.0], p < 0.001) and IADL (1.0 [0.0, 2.0] vs. 2.0 [1.0, 4.0], p < 0.001), as well as higher frailty levels on the CFS (7.0 [6.0, 7.0] vs. 6.0 [5.0, 7.0], p < 0.001). Dementia was more common among patients with delirium (49% vs 21%, p < 0.001). Patients with delirium also had a longer length of hospital stay (LOS, 13.0 [10.0, 18.0] vs. 12.0 [9.0, 15.0] days, p = 0.009), a lower likelihood to be discharged home (77% vs 86%, p = 0.049) and a significantly higher 90-day mortality (36% vs. 19%, p < 0.001) compared to those without delirium. Supplementary Table 1 compares patients across four delirium groups: hyperactive, hypoactive, mixed delirium subtypes, and those without delirium. Post hoc analyses revealed significant differences in ADL, IADL, and CFS scores between each delirium subtype and the no-delirium group. Additional differences among delirium subtypes emerged in ADL and albumin serum levels (lower in the hypoactive vs. hyperactive) and the rate of home discharge (lower in the mixed vs. hyperactive). At 90 days, mortality was highest in the mixed (41%) and hypoactive (44%) delirium subtypes, followed by the hyperactive (28%) and no-delirium (19%) groups (p = 0.003), with a significant difference observed between the hypoactive and no-delirium groups. Figure 1 illustrates OS according to delirium subtype or absence of delirium, with significant between-group differences at 90 days (log-rank p < 0.001). Figure 2 summarises the results of the univariable and multivariable Cox regression analyses. In adjusted models, both the hypoactive and mixed subtypes were independently associated with increased mortality risk (adjusted HR 2.03, 95% CI 1.13–3.64, p = 0.017, and adjusted HR 2.28, 95% CI 1.18–4.43, p = 0.014, respectively), while the hyperactive subtype showed no significant association (adjusted HR 1.25, 95% CI 0.71–2.21, p = 0.442) compared to the no-delirium group. Notably, frailty, as measured by the CFS, emerged as the only other independent predictor of 90-day mortality (adjusted HR 1.63, 95% CI 1.25–2.12, p < 0.001). DISCUSSION In this prospective 90-day follow-up study of very old patients admitted to an AGU for AHF, delirium was found in approximately one-third of cases. The hyperactive psychomotor subtype was the most common, accounting for nearly half of all cases, while hypoactive and mixed were observed in approximately one-third and one-fifth of cases, respectively. However, only the hypoactive and mixed psychomotor subtypes were independently associated with more than a twofold increased risk of 90-day post-discharge mortality, whereas no such association was found for the hyperactive. These findings highlight the critical relevance of actively identifying hypoactive and mixed delirium in older patients with AHF. Only a few studies have investigated the prevalence and incidence of delirium in very old patients with AHF. Pak et al. reported a 27.3% prevalence of delirium among 132 consecutive patients aged ≥ 80 years hospitalised for AHF (median age, 83 years; IQR, 75–87) [ 10 ]. A subsequent retrospective study in patients aged ≥ 75 years hospitalised for AHF found a prevalence of 24.0%[ 26 ], while a prospective registry study conducted in two Japanese cardiac intensive care units reported a prevalence of 26%[ 15 ]. Taken together, these estimates align with a substantial delirium burden in older AHF populations and are broadly consistent with the 33.1% rate observed in our cohort. Regarding psychomotor subtypes, Pak et al. identified hyperactive delirium in 86% of cases, with mixed and hypoactive accounting for only 8.3% and 5.6%, respectively [ 10 ]. Aikawa et al. reported hyperactive delirium in 60%, hypoactive in 28%, and mixed in 12% of patients [ 15 ]. In our cohort, the hyperactive delirium was also most common (48%), followed by hypoactive (31%) and mixed (21%). Differences in overall and subtype occurrence between our and previous studies likely reflect variation in delirium diagnostic procedures, population characteristics, and clinical settings. In particular, the older age and frailty profile of our cohort, combined with the diagnostic approach integrating a standardised screening tool with DSM-5–based confirmation, may have contributed to higher detection rates, particularly for the hypoactive and mixed subtypes, which are often under-recognized in routine care[ 27 ]. To our knowledge, no prior research has specifically examined survival according to delirium psychomotor subtypes in patients with AHF. Our data reveal a distinct impact of psychomotor subtypes on 90-day survival, with the mixed and hypoactive forms emerging as independent predictors of mortality. These results align with evidence from studies in stroke populations, as well as in subacute and post-acute care units, postoperative cohorts, and orthogeriatric patients [ 28 – 33 ]. Notably, frailty was the only other independent factor associated with poor survival, consistent with previous findings in hospitalised older adults[ 34 ]. The finding that only the hypoactive and mixed psychomotor subtypes, but not hyperactive, were associated with increased mortality may reflect underlying vulnerability shared with frailty. Recently, it has been proposed that both delirium and frailty can reflect manifestations of accelerated biological ageing[ 35 ], potentially explaining their frequent co-occurrence and poor outcomes when both conditions are present. An alternative explanation is that frailty may directly increase susceptibility to these delirium subtypes[ 36 ], which are themselves associated with a higher risk of mortality. Under this interpretation, hypoactive and mixed delirium might represent partial mediators in the pathway linking frailty to mortality. A third hypothesis is that the relationship between frailty and delirium subtypes is even more complex and not strictly unidirectional, with frailty predisposing to specific delirium subtypes and vice versa[ 35 ]. Further research is needed to clarify this complex interplay. Overall, our findings underscore the importance of systematic delirium screening and subtype differentiation in older patients with AHF. From a clinical perspective, this distinction may support more tailored and timely cardio-geriatric follow-up strategies. Early, multidimensional interventions—such as those delivered in specialized cardio-geriatric outpatient programs[ 37 ]—might be beneficial for this population, given the prognostic relevance of delirium and its association with subsequent cognitive and functional decline[ 38 ]. For researchers, these results highlight the need to further investigate the underlying mechanisms driving the differential outcomes associated with delirium psychomotor subtypes. Several limitations of this study should be acknowledged. First, the study relied on single-centre data, which may limit the generalisability of our findings to other clinical contexts. However, the use of a well-characterised cohort and standardised delirium assessment protocols strengthens the internal validity and ensures consistency in case identification. Second, delirium duration was not assessed, limiting our ability to evaluate its potential impact on patients’ survival. Third, although adjustments were made to account for potential confounders, the observational nature of the analysis means that residual confounding cannot be entirely ruled out. Lastly, the relationship between delirium and the use of sedative–hypnotic drugs has not been assessed due to the lack of data on drug administration during hospitalisation. The study also has several strengths. It is one of the first to comprehensively evaluate delirium by characterising its time of onset and psychomotor subtypes in older adults with AHF. Based on the available literature, this is the first study to examine the prognostic impact of delirium subtypes on survival using multivariable analysis, thereby accounting for potential confounders such as comorbidity burden, markers of disease severity, and frailty—a domain that is rarely assessed systematically in administrative or retrospective datasets. These strengths highlight the study’s contribution to advancing the understanding of delirium in AHF and could lay the groundwork for future multicentre investigations. CONCLUSIONS Delirium is a common and clinically relevant complication in older adults admitted to an acute geriatric ward with AHF. Specific psychomotor subtypes, particularly the hypoactive and mixed delirium, appear to carry a worse short-term prognosis. These findings emphasise the importance of identifying and characterising delirium subtypes in routine clinical assessment. Further studies are needed to validate these findings and to elucidate the mechanisms linking delirium to adverse outcomes in this population. Declarations ACKNOWLEDGEMENTS: The authors thank all the members of the Cardio-geriatrics Interest Group of the Geriatrics Unit of IRCCS San Gerardo dei Tintori – Monza, for the help given throughout the project. AUTHOR CONTRIBUTIONS: AF and CO contributed to the concept and design. EE, EC, and MM helped in acquisition of data. AF analyzed the data. AF, CO, and GB interpreted the data. AF, CO, and GB drafted the manuscript. GB, EP, AMO, MCF, EE, EC, MM, and AAB reviewed it critically for important intellectual content. CONFLICT OF INTEREST STATEMENT: The authors have no conflicts of interest to disclose. SPONSOR’S ROLE: none. References Diagnostic and Statistical Manual of Mental Disorders Fifth Edition Text Revision DSM-5-TR™ n.d Gibb K, Seeley A, Quinn T, Siddiqi N, Shenkin S, Rockwood K et al (2020) The consistent burden in published estimates of delirium occurrence in medical inpatients over four decades: a systematic review and meta-analysis study. Age Ageing 49:352–360. https://doi.org/10.1093/ageing/afaa040 Fuchs S, Bode L, Ernst J, Marquetand J, von Känel R, Böttger S (2020) Delirium in elderly patients: Prospective prevalence across hospital services. Gen Hosp Psychiatry 67:19–25. https://doi.org/10.1016/j.genhosppsych.2020.08.010 Bellelli G, Morandi A, Di Santo SG, Mazzone A, Cherubini A, Mossello E et al (2016) Delirium Day: a nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool. BMC Med 14:106. https://doi.org/10.1186/s12916-016-0649-8 Han QYC, Rodrigues NG, Klainin-Yobas P, Haugan G, Wu XV, Prevalence (2022) Risk Factors, and Impact of Delirium on Hospitalized Older Adults With Dementia: A Systematic Review and Meta-Analysis. J Am Med Dir Assoc 23:23–32e27. https://doi.org/10.1016/j.jamda.2021.09.008 Ornago AM, Pinardi E, Okoye C, Mazzola P, Ferrara MC, Finazzi A et al (2024) Eur Geriatr Med 15:1405–1413. https://doi.org/10.1007/s41999-024-01019-5 . Delirium prevalence and delirium literacy across Italian hospital wards: a secondary analysis of data from the World Delirium Awareness Day 2023 Witlox J, Eurelings LSM, de Jonghe JFM, Kalisvaart KJ, Eikelenboom P, van Gool WA (2010) Delirium in elderly patients and the risk of postdischarge mortality, institutionalization, and dementia: a meta-analysis. JAMA 304:443–451. https://doi.org/10.1001/jama.2010.1013 Uthamalingam S, Gurm GS, Daley M, Flynn J, Capodilupo R (2011) Usefulness of acute delirium as a predictor of adverse outcomes in patients > 65 years of age with acute decompensated heart failure. Am J Cardiol 108:402–408. https://doi.org/10.1016/j.amjcard.2011.03.059 Honda S, Nagai T, Sugano Y, Okada A, Asaumi Y, Aiba T et al (2016) Prevalence, determinants, and prognostic significance of delirium in patients with acute heart failure. Int J Cardiol 222:521–527. https://doi.org/10.1016/j.ijcard.2016.07.236 Pak M, Hara M, Miura S, Furuya M, Tamaki M, Okada T et al (2020) Delirium is associated with high mortality in older adult patients with acute decompensated heart failure. BMC Geriatr 20:524. https://doi.org/10.1186/s12877-020-01928-7 Irizarry-Caro JA, Kumar M, Wang Q, Rohant N, Goyal P, Damluji AA et al (2024) Impact of Frailty and Delirium Among Older Adults Admitted With Acute Decompensated Heart Failure. JACC Adv 3:101274. https://doi.org/10.1016/j.jacadv.2024.101274 McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M et al (2021) 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 42:3599–3726. https://doi.org/10.1093/eurheartj/ehab368 Butrous H, Hummel SL (2016) Heart Failure in Older Adults. Can J Cardiol 32:1140–1147. https://doi.org/10.1016/j.cjca.2016.05.005 Dai S, Walsh P, Wielgosz A, Gurevich Y, Bancej C, Morrison H (2012) Comorbidities and Mortality Associated With Hospitalized Heart Failure in Canada. Can J Cardiol 28:74–79. https://doi.org/10.1016/j.cjca.2011.05.002 Aikawa Y, Ogata S, Honda S, Nagai T, Murata S, Morii I et al (2024) Prolonged delirium during hospitalization is associated with worse long-term and short-term outcomes in patients with acute heart failure. Int J Cardiol 399:131776. https://doi.org/10.1016/j.ijcard.2024.131776 REDCap (2024) accessed November 19, n.d. https://project-redcap.org / von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP et al (2008) The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol 61:344–349. https://doi.org/10.1016/j.jclinepi.2007.11.008 Welch J, Dean J, Hartin J (2022) Using NEWS2: an essential component of reliable clinical assessment. Clin Med 22:509–513. https://doi.org/10.7861/clinmed.2022-0435 Charlson ME, Pompei P, Ales KL, MacKenzie CR (1987) A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 40:373–383. https://doi.org/10.1016/0021-9681(87)90171-8 Lawton MP, Brody EM (1969) Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist 9:179–186 Theou O, Pérez-Zepeda MU, van der Valk AM, Searle SD, Howlett SE, Rockwood K (2021) A classification tree to assist with routine scoring of the Clinical Frailty Scale. Age Ageing 50:1406–1411. https://doi.org/10.1093/ageing/afab006 Bellelli G, Morandi A, Davis DHJ, Mazzola P, Turco R, Gentile S et al (2014) Validation of the 4AT, a new instrument for rapid delirium screening: a study in 234 hospitalised older people. Age Ageing 43:496–502. https://doi.org/10.1093/ageing/afu021 Burton JK, Soiza RL, Quinn TJ, SIGN 168 guideline development group (2024) Guideline summary: assessment, diagnosis, care and support for people with dementia and their carers [Scottish Intercollegiate Guidelines Network SIGN Guideline 168]. Age Ageing 53:afae147. https://doi.org/10.1093/ageing/afae147 Lachance C, Wright M-D (2019) Avoidance of Physical Restraint Use among Hospitalized Older Adults: A Review of Clinical Effectiveness and Guidelines. Canadian Agency for Drugs and Technologies in Health, Ottawa (ON) R: The R Project for Statistical Computing n.d. https://www.r-project.org/ (2024) Miao L, Shen X, Du Z, Liao J (2024) Nutritional status and triglyceride-glucose index influence delirium in elderly heart failure patients. Sci Rep 14:25235. https://doi.org/10.1038/s41598-024-77573-6 Bellelli G, Nobili A, Annoni G, Morandi A, Djade CD, Meagher DJ et al (2015) Under-detection of delirium and impact of neurocognitive deficits on in-hospital mortality among acute geriatric and medical wards. Eur J Intern Med 26:696–704. https://doi.org/10.1016/j.ejim.2015.08.006 Kiely DK, Jones RN, Bergmann MA, Marcantonio ER (2007) Association between psychomotor activity delirium subtypes and mortality among newly admitted post-acute facility patients. J Gerontol Biol Sci Med Sci 62:174–179. https://doi.org/10.1093/gerona/62.2.174 Bellelli G, Carnevali L, Corsi M, Morandi A, Zambon A, Mazzola P et al (2018) The impact of psychomotor subtypes and duration of delirium on 6-month mortality in hip-fractured elderly patients. Int J Geriatr Psychiatry 33:1229–1235. https://doi.org/10.1002/gps.4914 Fialho Silva IT, Assis Lopes P, Timotio Almeida T, Ramos SC, Caliman Fontes AT, Guimarães Silva D et al (2021) Impact of Delirium and Its Motor Subtypes on Stroke Outcomes. Stroke 52:1322–1329. https://doi.org/10.1161/STROKEAHA.120.026425 Gual N, Inzitari M, Carrizo G, Calle A, Udina C, Yuste A et al (2018) Delirium Subtypes and Associated Characteristics in Older Patients With Exacerbation of Chronic Conditions. Am J Geriatr Psychiatry Off J Am Assoc Geriatr Psychiatry 26:1204–1212. https://doi.org/10.1016/j.jagp.2018.07.003 Meagher DJ, Leonard M, Donnelly S, Conroy M, Adamis D, Trzepacz PT (2011) A longitudinal study of motor subtypes in delirium: relationship with other phenomenology, etiology, medication exposure and prognosis. J Psychosom Res 71:395–403. https://doi.org/10.1016/j.jpsychores.2011.06.001 Robinson TN, Raeburn CD, Tran ZV, Brenner LA, Moss M (2011) Motor subtypes of postoperative delirium in older adults. Arch Surg Chic Ill 1960 146:295–300. https://doi.org/10.1001/archsurg.2011.14 Cunha AIL, Veronese N, de Melo Borges S, Ricci NA (2019) Frailty as a predictor of adverse outcomes in hospitalized older adults: A systematic review and meta-analysis. Ageing Res Rev 56:100960. https://doi.org/10.1016/j.arr.2019.100960 Bellelli G, Triolo F, Ferrara MC, Deiner SG, Morandi A, Cesari M et al (2024) Delirium and frailty in older adults: Clinical overlap and biological underpinnings. J Intern Med 296:382–398. https://doi.org/10.1111/joim.20014 Ghezzi ES, Greaves D, Boord MS, Davis D, Knayfati S, Astley JM et al (2022) How do predisposing factors differ between delirium motor subtypes? A systematic review and meta-analysis. Age Ageing 51:afac200. https://doi.org/10.1093/ageing/afac200 Okoye C, Mazzarone T, Finazzi A, Daniela G, Bruni AA, Maccioni L et al (2025) Outcomes of early post-discharge cardio-geriatric care in frail patients after acute heart failure: a before-and-after study. BMC Geriatr 25:1–10. https://doi.org/10.1186/s12877-025-05883-z Tesfaye Y, Davis CR, Hull MJ, Greaves D, du Preez J, Johns S et al (2025) Long-term clinical outcomes of delirium after hospital discharge: a systematic review and meta-analysis. Age Ageing 54:afaf188. https://doi.org/10.1093/ageing/afaf188 Supplementary Files SupplementaryMaterial.docx S. Table 1. Patients’ baseline characteristics according to the delirium subtypes and no-delirium. S. Figure 1. Flowchart of the study. S. Figure 2. Characteristics of delirium based on time of onset and motor subtypes. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Major revisions 30 Nov, 2025 Reviewers agreed at journal 06 Oct, 2025 Reviewers invited by journal 30 Sep, 2025 Editor invited by journal 23 Sep, 2025 Editor assigned by journal 23 Sep, 2025 First submitted to journal 21 Sep, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7668204","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":522854444,"identity":"5fd0e2fe-17a8-4d47-8b10-461980e9c3c6","order_by":0,"name":"Alberto 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1","display":"","copyAsset":false,"role":"figure","size":628409,"visible":true,"origin":"","legend":"\u003cp\u003eOverall survival of AHF patients by delirium subtypes and absence of delirium during Hospitalization.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7668204/v1/7175fee6672d06e90ae6360e.png"},{"id":93539804,"identity":"4f70c6dd-1a17-45ac-80e6-c8c1a41e8c10","added_by":"auto","created_at":"2025-10-15 02:20:55","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":435432,"visible":true,"origin":"","legend":"\u003cp\u003eDelirium subtypes’ impact on 90-day mortality: results from univariable analysis (blue) and multivariable analysis (red).\u003c/p\u003e\n\u003cp\u003eAbbreviations: CCI, Charlson comorbidity index; CFS, clinical frailty scale; m-NEWS2, modified-National Early Warning Score 2.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7668204/v1/e71ecd8c61885d641e3eda53.png"},{"id":93541182,"identity":"251e0a4d-32f9-49c7-b0ff-ab36b0743655","added_by":"auto","created_at":"2025-10-15 02:29:01","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1389602,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7668204/v1/cb06c9d6-fc17-4d17-a2b6-8b996d206812.pdf"},{"id":93539806,"identity":"5358d487-57be-4497-a70c-93cd10d3e8c3","added_by":"auto","created_at":"2025-10-15 02:20:55","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":828767,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eS. Table 1. \u003c/strong\u003ePatients’ baseline characteristics according to the delirium subtypes and no-delirium.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eS. Figure 1. \u003c/strong\u003eFlowchart of the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eS. Figure 2. \u003c/strong\u003eCharacteristics of delirium based on time of onset and motor subtypes.\u003c/p\u003e","description":"","filename":"SupplementaryMaterial.docx","url":"https://assets-eu.researchsquare.com/files/rs-7668204/v1/92af43c4a3af076f32df0464.docx"}],"financialInterests":"","formattedTitle":"Impact of Hypoactive and Mixed Delirium on Short-Term Survival in Older Adults Hospitalised for Acute Heart Failure: A Prospective Study in an Acute Geriatric Unit","fulltext":[{"header":"Key summary points","content":"\u003cp\u003e\u003cstrong\u003eAim:\u003c/strong\u003e to determine the prevalence and incidence of delirium subtypes in older adults with AHF and evaluate their impact on 90-day survival.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFindings:\u003c/strong\u003e among 399 patients (median age 87.4 years), delirium occurred in 33%, with 48% hyperactive, 31% hypoactive, and 21% mixed. Only hypoactive and mixed subtypes were independently associated with increased 90-day mortality.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMessage:\u003c/strong\u003e early recognition of delirium psychomotor subtypes may help risk stratification and tailored care.\u003c/p\u003e"},{"header":"INTRODUCTION","content":"\u003cp\u003eDelirium is a neuropsychiatric syndrome characterised by acute dysfunction in attention and awareness, typically with a fluctuating course, and triggered by acute medical illness[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. It is common among hospitalised patients and is associated with multiple adverse outcomes[\u003cspan additionalcitationids=\"CR3 CR4 CR5 CR6\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Clinically, delirium can be categorised into three psychomotor subtypes: hyperactive, hypoactive, and mixed. Hyperactive delirium is characterized by increased motor activity, mood lability, agitation, and/or refusal to cooperate with medical care; hypoactive delirium presents with reduced activity and speech, sluggishness, and lethargy approaching stupor. Mixed delirium involves alternating features of both[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e\u003cp\u003ePrevious studies suggest that delirium affects up to one in four adults hospitalised with acute heart failure (AHF) [\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], with significant implications for both survival and discharge outcomes [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. However, most evidence comes from relatively younger populations, while patients over 80 years \u0026mdash; paradoxically, the fastest-growing group hospitalised for AHF [\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] \u0026mdash; remain underrepresented. In this older cohort, existing studies offer limited data on the prevalence, incidence, and motor subtypes of delirium, and their prognostic relevance remains unclear[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. In particular, the association between delirium subtypes and mortality in AHF remains poorly understood.\u003c/p\u003e\u003cp\u003eTo address this gap, we investigated delirium in a cohort of patients aged 80 or older admitted to an acute geriatric unit (AGU) for AHF, focusing on its prevalence, incidence, and the impact of psychomotor subtypes on 90-day post-discharge survival.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy design, data collection, and ethics statement\u003c/h2\u003e\u003cp\u003eThis is a prospective observational study conducted on older adults admitted to the AGU of a tertiary referral hospital in Northern Italy. Patients were enrolled consecutively from April 2022 to November 2024. All patients who provided consent either directly or through a next of kin were enrolled in the study. Data collected included biological, sociodemographic, and social information, as well as details regarding hospitalisation and 12-month mortality outcomes. We included patients discharged alive following hospitalisation for AHF.\u003c/p\u003e\u003cp\u003eThe data were collected using an electronic case report form (eCRF) by trained personnel using Research Electronic Data Capture (REDCap)[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The study was approved by the Lombardy Regional Ethics Committee (Deliberation No. 1205, December 14, 2022) and conducted in accordance with the principles of the Declaration of Helsinki. The results are reported in compliance with the STROBE statement[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eBaseline clinical variables\u003c/h3\u003e\n\u003cp\u003eAHF was defined as the rapid or gradual onset of symptoms and/or signs of heart failure requiring unplanned hospital admission[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. When available, the left ventricular ejection fraction (LVEF) measured within the prior year was used to classify HF subtype, in accordance with international guidelines[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Routine blood tests were performed within 48 hours of admission. NT-proBNP measurement was left to the discretion of the attending physician, reflecting the real-world nature of the study. Upon admission, National Early Warning Score 2 (NEWS-2) parameters\u0026mdash;including respiratory rate, oxygen saturation (with or without hypercapnia), oxygen supplementation, blood pressure, heart rate, consciousness level, and temperature\u0026mdash;were assessed[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. A routine comprehensive geriatric assessment (CGA) was also conducted, including sociodemographic data, Charlson Comorbidity Index (CCI)[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], functional status (Activities of Daily Living [ADL] and Instrumental Activities of Daily Living [IADL])[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], nutritional status (albumin levels), and prior history of dementia, identified through medical records or previous prescriptions for acetylcholinesterase inhibitors or memantine. The Clinical Frailty Scale (CFS) was scored by a senior geriatrician, according to a standardized classification tree[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003eDelirium\u003c/h3\u003e\n\u003cp\u003eDelirium was assessed on admission and daily during hospitalisation by a senior geriatrician using the 4AT [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The 4AT is a validated screening tool for the detection of delirium, with scores\u0026thinsp;\u0026ge;\u0026thinsp;4 indicating possible delirium. In such cases, the diagnosis was confirmed according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM\u0026ndash;5)[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Delirium was classified as prevalent if present at admission and as incident if it developed during the hospital stay. Psychomotor subtypes were identified using DSM\u0026ndash;5 criteria and classified as hyperactive, hypoactive, or mixed[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAll patients received an individualised delirium prevention and management plan shortly after admission, including medication review and interventions addressing common risk factors. In patients with dementia, non-pharmacological strategies were implemented through referral to occupational therapy, in accordance with established guidelines[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. When pharmacological treatment was required, trazodone or haloperidol was preferred, while benzodiazepines and drugs with high anticholinergic burden were avoided. If severe agitation posed a safety risk and was unresponsive to other measures, physical restraints (soft devices or straps) were used as a last resort, following international guidelines[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Their use required informed consent from patients or next of kin, obtained at admission, and was subject to regular and close multidisciplinary review.\u003c/p\u003e\n\u003ch3\u003eFollow-up and outcome variable\u003c/h3\u003e\n\u003cp\u003eFollow-up data were retrieved by a trained data manager via the Lombardy Regional Socio-Healthcare Information System portal. For each patient, the date of hospital discharge and, where applicable, the date of death were recorded. These variables were used to derive 90-day post-discharge survival, expressed both as a time-to-event variable (days from discharge to death, right-censored at 90 days) and as a binary variable indicating survival status at 90 days post-discharge (alive or deceased).\u003c/p\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eSocio-demographic and clinical characteristics were analysed using descriptive statistics. Categorical variables were summarised as absolute frequencies and percentages, while continuous variables were expressed as medians with interquartile ranges (IQRs). Group comparisons were performed using the Kruskal\u0026ndash;Wallis test for continuous variables and Pearson\u0026rsquo;s chi-square test for categorical variables. Post-hoc pairwise comparisons were conducted using Dunn\u0026rsquo;s test and pairwise chi-square tests, both with Bonferroni correction.\u003c/p\u003e\u003cp\u003eOverall survival (OS) was defined as the time from hospital discharge to death from any cause. Patients who were alive 90 days after discharge were censored at that time point. OS was estimated using the Kaplan-Meier method, with survival curves compared between groups using the log-rank test. Univariable and multivariable Cox proportional-hazards regression models were fitted to evaluate the association between socio-demographic, clinical characteristics, and OS. Selection of explanatory variables was informed by clinical relevance and considering previous literature[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. A modified version of the NEWS2 score, excluding consciousness from the global score, was employed to avoid collinearity with delirium.\u003c/p\u003e\u003cp\u003eAll statistical analyses were conducted using R software, version 4.5.1 (2025-06-13)[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e\u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eAmong the 2,212 patients admitted to the AGU during the study period, 444 (20.1%) were diagnosed with AHF at admission (\u003cb\u003eSupplementary Fig.\u0026nbsp;1\u003c/b\u003e). Of these, 45 patients (10.1%) died during hospitalisation, resulting in 399 patients eligible for final analysis (median age 87 years [IQR, 83.9\u0026thinsp;\u0026minus;\u0026thinsp;90.6]; 52% female).\u003c/p\u003e\u003cp\u003eDelirium was diagnosed in 132 patients (33.1%), of whom 55 (13.8%) had prevalent and 77 (19.2%) incident delirium. The hyperactive subtype was the most frequent (48%, 64/132), followed by hypoactive (31%, 41/132) and mixed (21%, 27/132) subtypes. The distribution of psychomotor subtypes is shown in \u003cb\u003eSupplementary Fig.\u0026nbsp;2\u003c/b\u003e.\u003c/p\u003e\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the characteristics of the overall study population, stratified by delirium status. No significant differences in age or CCI were observed between patients with and without delirium. The prevalence of ischemic heart disease, atrial fibrillation, chronic obstructive pulmonary disease (COPD), diabetes, and chronic kidney disease was comparable between groups. Heart failure with preserved ejection fraction (HFpEF) was the predominant phenotype in both groups, accounting for over half of cases with available LVEF data.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMain characteristics of the overall sample and according to delirium occurrence during hospitalisation.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOverall\u003c/p\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;399)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eDelirium\u003c/p\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;132)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNo delirium\u003c/p\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;267)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge, median [IQR]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e87.4 [83.9, 90.6]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e88.2 [83.6, 91.3]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e87.4 [84.0, 90.3]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e207 (52)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e64 (48)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e143 (54)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eADL, median [IQR]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4.0 [1.0, 6.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.0 [1.0, 5.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5.0 [2.0, 6.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIADL, median [IQR]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.0 [0.0, 3.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.0 [0.0, 2.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.0 [1.0, 4.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCFS, median [IQR]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6.0 [5.0, 7.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7.0 [6.0, 7.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6.0 [5.0, 7.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlbumin (g/L), median [IQR]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e34.0 [30.0, 37.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e33.5 [30.5, 37.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e34.0 [30.0, 36.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDementia, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e117 (29)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e62 (47)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e55 (21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCCI, median [IQR]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6.0 [5.0, 8.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6.0 [5.0, 8.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6.0 [5.0, 8.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIschemic heart disease, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e95 (24)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e27 (20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e68 (26)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAtrial fibrillation, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e192 (48)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e59 (45)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e135 (50)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCOPD, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e81 (20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28 (21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e53 (20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes mellitus\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e119 (30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e37 (28)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e82 (31)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCKD, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e155 (39)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e42 (32)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e117 (42)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.062\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eType of HF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHFmrEF, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e52 (13)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e22 (17)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e30 (11)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHFpEF, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e122 (31)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e36 (27)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e86 (32)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHFrEF, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e41 (10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13 (9.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e28 (10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUnknown, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e184 (46)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e61 (46)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e123 (46)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNT-proBNP\u0026dagger; (pg/mL), median [IQR]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6,341.0 [3,088.0, 13,276.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6,558.0 [2,732.0, 12,511.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6,088.0 [3,150.0, 13,364.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLOS, median [IQR]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12.0 [9.0, 16.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13.0 [10.0, 18.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e12.0 [9.0, 15.0]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.009\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDischarged home, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e330 (83%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e102 (77%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e228 (86%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.049\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e90-days mortality, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e99 (25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e47 (36)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e52 (19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003eAbbreviations: ADL, activities of daily living; CCI, Charlson comorbidity index; CKD, chronic kidney disease; CFS, clinical frailty scale; COPD, chronic obstructive pulmonary disease; IADL, instrumental activities of daily living; HF, heart failure; HFrEF, with reduced Ejection Fraction; HFmrEF, with mildly reduced ejection fraction; HFpEF, with preserved ejection fraction; LOS, length of stay.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u0026dagger;Data available for 233 patients (58% of the total cohort).\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003ePatients with delirium showed greater functional impairment in ADL (3.0 [1.0, 5.0] vs. 5.0 [2.0, 6.0], p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and IADL (1.0 [0.0, 2.0] vs. 2.0 [1.0, 4.0], p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), as well as higher frailty levels on the CFS (7.0 [6.0, 7.0] vs. 6.0 [5.0, 7.0], p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Dementia was more common among patients with delirium (49% vs 21%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003cp\u003ePatients with delirium also had a longer length of hospital stay (LOS, 13.0 [10.0, 18.0] vs. 12.0 [9.0, 15.0] days, p\u0026thinsp;=\u0026thinsp;0.009), a lower likelihood to be discharged home (77% vs 86%, p\u0026thinsp;=\u0026thinsp;0.049) and a significantly higher 90-day mortality (36% vs. 19%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) compared to those without delirium.\u003c/p\u003e\u003cp\u003e\u003cb\u003eSupplementary Table\u0026nbsp;1\u003c/b\u003e compares patients across four delirium groups: hyperactive, hypoactive, mixed delirium subtypes, and those without delirium. Post hoc analyses revealed significant differences in ADL, IADL, and CFS scores between each delirium subtype and the no-delirium group. Additional differences among delirium subtypes emerged in ADL and albumin serum levels (lower in the hypoactive vs. hyperactive) and the rate of home discharge (lower in the mixed vs. hyperactive).\u003c/p\u003e\u003cp\u003eAt 90 days, mortality was highest in the mixed (41%) and hypoactive (44%) delirium subtypes, followed by the hyperactive (28%) and no-delirium (19%) groups (p\u0026thinsp;=\u0026thinsp;0.003), with a significant difference observed between the hypoactive and no-delirium groups.\u003c/p\u003e\u003cp\u003eFigure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e illustrates OS according to delirium subtype or absence of delirium, with significant between-group differences at 90 days (log-rank p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Figure\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e summarises the results of the univariable and multivariable Cox regression analyses. In adjusted models, both the hypoactive and mixed subtypes were independently associated with increased mortality risk (adjusted HR 2.03, 95% CI 1.13\u0026ndash;3.64, p\u0026thinsp;=\u0026thinsp;0.017, and adjusted HR 2.28, 95% CI 1.18\u0026ndash;4.43, p\u0026thinsp;=\u0026thinsp;0.014, respectively), while the hyperactive subtype showed no significant association (adjusted HR 1.25, 95% CI 0.71\u0026ndash;2.21, p\u0026thinsp;=\u0026thinsp;0.442) compared to the no-delirium group. Notably, frailty, as measured by the CFS, emerged as the only other independent predictor of 90-day mortality (adjusted HR 1.63, 95% CI 1.25\u0026ndash;2.12, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eIn this prospective 90-day follow-up study of very old patients admitted to an AGU for AHF, delirium was found in approximately one-third of cases. The hyperactive psychomotor subtype was the most common, accounting for nearly half of all cases, while hypoactive and mixed were observed in approximately one-third and one-fifth of cases, respectively. However, only the hypoactive and mixed psychomotor subtypes were independently associated with more than a twofold increased risk of 90-day post-discharge mortality, whereas no such association was found for the hyperactive. These findings highlight the critical relevance of actively identifying hypoactive and mixed delirium in older patients with AHF.\u003c/p\u003e\u003cp\u003eOnly a few studies have investigated the prevalence and incidence of delirium in very old patients with AHF. Pak et al. reported a 27.3% prevalence of delirium among 132 consecutive patients aged\u0026thinsp;\u0026ge;\u0026thinsp;80 years hospitalised for AHF (median age, 83 years; IQR, 75\u0026ndash;87) [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. A subsequent retrospective study in patients aged\u0026thinsp;\u0026ge;\u0026thinsp;75 years hospitalised for AHF found a prevalence of 24.0%[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e], while a prospective registry study conducted in two Japanese cardiac intensive care units reported a prevalence of 26%[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Taken together, these estimates align with a substantial delirium burden in older AHF populations and are broadly consistent with the 33.1% rate observed in our cohort.\u003c/p\u003e\u003cp\u003eRegarding psychomotor subtypes, Pak et al. identified hyperactive delirium in 86% of cases, with mixed and hypoactive accounting for only 8.3% and 5.6%, respectively [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Aikawa et al. reported hyperactive delirium in 60%, hypoactive in 28%, and mixed in 12% of patients [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. In our cohort, the hyperactive delirium was also most common (48%), followed by hypoactive (31%) and mixed (21%). Differences in overall and subtype occurrence between our and previous studies likely reflect variation in delirium diagnostic procedures, population characteristics, and clinical settings. In particular, the older age and frailty profile of our cohort, combined with the diagnostic approach integrating a standardised screening tool with DSM-5\u0026ndash;based confirmation, may have contributed to higher detection rates, particularly for the hypoactive and mixed subtypes, which are often under-recognized in routine care[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eTo our knowledge, no prior research has specifically examined survival according to delirium psychomotor subtypes in patients with AHF. Our data reveal a distinct impact of psychomotor subtypes on 90-day survival, with the mixed and hypoactive forms emerging as independent predictors of mortality. These results align with evidence from studies in stroke populations, as well as in subacute and post-acute care units, postoperative cohorts, and orthogeriatric patients [\u003cspan additionalcitationids=\"CR29 CR30 CR31 CR32\" citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Notably, frailty was the only other independent factor associated with poor survival, consistent with previous findings in hospitalised older adults[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe finding that only the hypoactive and mixed psychomotor subtypes, but not hyperactive, were associated with increased mortality may reflect underlying vulnerability shared with frailty. Recently, it has been proposed that both delirium and frailty can reflect manifestations of accelerated biological ageing[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e], potentially explaining their frequent co-occurrence and poor outcomes when both conditions are present. An alternative explanation is that frailty may directly increase susceptibility to these delirium subtypes[\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e], which are themselves associated with a higher risk of mortality. Under this interpretation, hypoactive and mixed delirium might represent partial mediators in the pathway linking frailty to mortality. A third hypothesis is that the relationship between frailty and delirium subtypes is even more complex and not strictly unidirectional, with frailty predisposing to specific delirium subtypes and vice versa[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Further research is needed to clarify this complex interplay.\u003c/p\u003e\u003cp\u003eOverall, our findings underscore the importance of systematic delirium screening and subtype differentiation in older patients with AHF. From a clinical perspective, this distinction may support more tailored and timely cardio-geriatric follow-up strategies. Early, multidimensional interventions\u0026mdash;such as those delivered in specialized cardio-geriatric outpatient programs[\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]\u0026mdash;might be beneficial for this population, given the prognostic relevance of delirium and its association with subsequent cognitive and functional decline[\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. For researchers, these results highlight the need to further investigate the underlying mechanisms driving the differential outcomes associated with delirium psychomotor subtypes.\u003c/p\u003e\u003cp\u003eSeveral limitations of this study should be acknowledged. First, the study relied on single-centre data, which may limit the generalisability of our findings to other clinical contexts. However, the use of a well-characterised cohort and standardised delirium assessment protocols strengthens the internal validity and ensures consistency in case identification. Second, delirium duration was not assessed, limiting our ability to evaluate its potential impact on patients\u0026rsquo; survival. Third, although adjustments were made to account for potential confounders, the observational nature of the analysis means that residual confounding cannot be entirely ruled out. Lastly, the relationship between delirium and the use of sedative\u0026ndash;hypnotic drugs has not been assessed due to the lack of data on drug administration during hospitalisation.\u003c/p\u003e\u003cp\u003eThe study also has several strengths. It is one of the first to comprehensively evaluate delirium by characterising its time of onset and psychomotor subtypes in older adults with AHF. Based on the available literature, this is the first study to examine the prognostic impact of delirium subtypes on survival using multivariable analysis, thereby accounting for potential confounders such as comorbidity burden, markers of disease severity, and frailty\u0026mdash;a domain that is rarely assessed systematically in administrative or retrospective datasets. These strengths highlight the study\u0026rsquo;s contribution to advancing the understanding of delirium in AHF and could lay the groundwork for future multicentre investigations.\u003c/p\u003e"},{"header":"CONCLUSIONS","content":"\u003cp\u003eDelirium is a common and clinically relevant complication in older adults admitted to an acute geriatric ward with AHF. Specific psychomotor subtypes, particularly the hypoactive and mixed delirium, appear to carry a worse short-term prognosis. These findings emphasise the importance of identifying and characterising delirium subtypes in routine clinical assessment. Further studies are needed to validate these findings and to elucidate the mechanisms linking delirium to adverse outcomes in this population.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eACKNOWLEDGEMENTS:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank all the members of the Cardio-geriatrics Interest Group of the Geriatrics Unit of IRCCS San Gerardo dei Tintori\u0026nbsp;\u0026ndash;\u0026nbsp;Monza, for the help given throughout the project.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAUTHOR CONTRIBUTIONS:\u0026nbsp;\u003c/strong\u003eAF and CO contributed to the concept and design. EE, EC, and MM helped in acquisition of data. AF analyzed the data. AF, CO, and GB interpreted the data. AF, CO, and GB drafted the manuscript. GB, EP, AMO, MCF, EE, EC, MM, and AAB reviewed it critically for important intellectual content.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCONFLICT OF INTEREST STATEMENT:\u0026nbsp;\u003c/strong\u003eThe authors have no conflicts of interest to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSPONSOR\u0026rsquo;S ROLE:\u003c/strong\u003e none.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eDiagnostic and Statistical Manual of Mental Disorders Fifth Edition Text Revision DSM-5-TR\u0026trade; n.d\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGibb K, Seeley A, Quinn T, Siddiqi N, Shenkin S, Rockwood K et al (2020) The consistent burden in published estimates of delirium occurrence in medical inpatients over four decades: a systematic review and meta-analysis study. Age Ageing 49:352\u0026ndash;360. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1093/ageing/afaa040\u003c/span\u003e\u003cspan address=\"10.1093/ageing/afaa040\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFuchs S, Bode L, Ernst J, Marquetand J, von K\u0026auml;nel R, B\u0026ouml;ttger S (2020) Delirium in elderly patients: Prospective prevalence across hospital services. Gen Hosp Psychiatry 67:19\u0026ndash;25. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.genhosppsych.2020.08.010\u003c/span\u003e\u003cspan address=\"10.1016/j.genhosppsych.2020.08.010\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBellelli G, Morandi A, Di Santo SG, Mazzone A, Cherubini A, Mossello E et al (2016) Delirium Day: a nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool. BMC Med 14:106. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/s12916-016-0649-8\u003c/span\u003e\u003cspan address=\"10.1186/s12916-016-0649-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHan QYC, Rodrigues NG, Klainin-Yobas P, Haugan G, Wu XV, Prevalence (2022) Risk Factors, and Impact of Delirium on Hospitalized Older Adults With Dementia: A Systematic Review and Meta-Analysis. J Am Med Dir Assoc 23:23\u0026ndash;32e27. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jamda.2021.09.008\u003c/span\u003e\u003cspan address=\"10.1016/j.jamda.2021.09.008\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOrnago AM, Pinardi E, Okoye C, Mazzola P, Ferrara MC, Finazzi A et al (2024) Eur Geriatr Med 15:1405\u0026ndash;1413. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s41999-024-01019-5\u003c/span\u003e\u003cspan address=\"10.1007/s41999-024-01019-5\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Delirium prevalence and delirium literacy across Italian hospital wards: a secondary analysis of data from the World Delirium Awareness Day 2023\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWitlox J, Eurelings LSM, de Jonghe JFM, Kalisvaart KJ, Eikelenboom P, van Gool WA (2010) Delirium in elderly patients and the risk of postdischarge mortality, institutionalization, and dementia: a meta-analysis. JAMA 304:443\u0026ndash;451. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1001/jama.2010.1013\u003c/span\u003e\u003cspan address=\"10.1001/jama.2010.1013\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eUthamalingam S, Gurm GS, Daley M, Flynn J, Capodilupo R (2011) Usefulness of acute delirium as a predictor of adverse outcomes in patients\u0026thinsp;\u0026gt;\u0026thinsp;65 years of age with acute decompensated heart failure. Am J Cardiol 108:402\u0026ndash;408. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.amjcard.2011.03.059\u003c/span\u003e\u003cspan address=\"10.1016/j.amjcard.2011.03.059\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHonda S, Nagai T, Sugano Y, Okada A, Asaumi Y, Aiba T et al (2016) Prevalence, determinants, and prognostic significance of delirium in patients with acute heart failure. Int J Cardiol 222:521\u0026ndash;527. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.ijcard.2016.07.236\u003c/span\u003e\u003cspan address=\"10.1016/j.ijcard.2016.07.236\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePak M, Hara M, Miura S, Furuya M, Tamaki M, Okada T et al (2020) Delirium is associated with high mortality in older adult patients with acute decompensated heart failure. BMC Geriatr 20:524. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/s12877-020-01928-7\u003c/span\u003e\u003cspan address=\"10.1186/s12877-020-01928-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eIrizarry-Caro JA, Kumar M, Wang Q, Rohant N, Goyal P, Damluji AA et al (2024) Impact of Frailty and Delirium Among Older Adults Admitted With Acute Decompensated Heart Failure. JACC Adv 3:101274. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jacadv.2024.101274\u003c/span\u003e\u003cspan address=\"10.1016/j.jacadv.2024.101274\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMcDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, B\u0026ouml;hm M et al (2021) 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 42:3599\u0026ndash;3726. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1093/eurheartj/ehab368\u003c/span\u003e\u003cspan address=\"10.1093/eurheartj/ehab368\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eButrous H, Hummel SL (2016) Heart Failure in Older Adults. Can J Cardiol 32:1140\u0026ndash;1147. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.cjca.2016.05.005\u003c/span\u003e\u003cspan address=\"10.1016/j.cjca.2016.05.005\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDai S, Walsh P, Wielgosz A, Gurevich Y, Bancej C, Morrison H (2012) Comorbidities and Mortality Associated With Hospitalized Heart Failure in Canada. Can J Cardiol 28:74\u0026ndash;79. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.cjca.2011.05.002\u003c/span\u003e\u003cspan address=\"10.1016/j.cjca.2011.05.002\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAikawa Y, Ogata S, Honda S, Nagai T, Murata S, Morii I et al (2024) Prolonged delirium during hospitalization is associated with worse long-term and short-term outcomes in patients with acute heart failure. Int J Cardiol 399:131776. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.ijcard.2024.131776\u003c/span\u003e\u003cspan address=\"10.1016/j.ijcard.2024.131776\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eREDCap (2024) accessed November 19, n.d. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://project-redcap.org\u003c/span\u003e\u003cspan address=\"https://project-redcap.org\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e/\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003evon Elm E, Altman DG, Egger M, Pocock SJ, G\u0026oslash;tzsche PC, Vandenbroucke JP et al (2008) The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol 61:344\u0026ndash;349. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jclinepi.2007.11.008\u003c/span\u003e\u003cspan address=\"10.1016/j.jclinepi.2007.11.008\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWelch J, Dean J, Hartin J (2022) Using NEWS2: an essential component of reliable clinical assessment. Clin Med 22:509\u0026ndash;513. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.7861/clinmed.2022-0435\u003c/span\u003e\u003cspan address=\"10.7861/clinmed.2022-0435\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCharlson ME, Pompei P, Ales KL, MacKenzie CR (1987) A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 40:373\u0026ndash;383. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/0021-9681(87)90171-8\u003c/span\u003e\u003cspan address=\"10.1016/0021-9681(87)90171-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLawton MP, Brody EM (1969) Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist 9:179\u0026ndash;186\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTheou O, P\u0026eacute;rez-Zepeda MU, van der Valk AM, Searle SD, Howlett SE, Rockwood K (2021) A classification tree to assist with routine scoring of the Clinical Frailty Scale. Age Ageing 50:1406\u0026ndash;1411. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1093/ageing/afab006\u003c/span\u003e\u003cspan address=\"10.1093/ageing/afab006\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBellelli G, Morandi A, Davis DHJ, Mazzola P, Turco R, Gentile S et al (2014) Validation of the 4AT, a new instrument for rapid delirium screening: a study in 234 hospitalised older people. Age Ageing 43:496\u0026ndash;502. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1093/ageing/afu021\u003c/span\u003e\u003cspan address=\"10.1093/ageing/afu021\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBurton JK, Soiza RL, Quinn TJ, SIGN 168 guideline development group (2024) Guideline summary: assessment, diagnosis, care and support for people with dementia and their carers [Scottish Intercollegiate Guidelines Network SIGN Guideline 168]. Age Ageing 53:afae147. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1093/ageing/afae147\u003c/span\u003e\u003cspan address=\"10.1093/ageing/afae147\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLachance C, Wright M-D (2019) Avoidance of Physical Restraint Use among Hospitalized Older Adults: A Review of Clinical Effectiveness and Guidelines. Canadian Agency for Drugs and Technologies in Health, Ottawa (ON)\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eR: The R Project for Statistical Computing n.d. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.r-project.org/\u003c/span\u003e\u003cspan address=\"https://www.r-project.org/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2024)\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMiao L, Shen X, Du Z, Liao J (2024) Nutritional status and triglyceride-glucose index influence delirium in elderly heart failure patients. Sci Rep 14:25235. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s41598-024-77573-6\u003c/span\u003e\u003cspan address=\"10.1038/s41598-024-77573-6\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBellelli G, Nobili A, Annoni G, Morandi A, Djade CD, Meagher DJ et al (2015) Under-detection of delirium and impact of neurocognitive deficits on in-hospital mortality among acute geriatric and medical wards. Eur J Intern Med 26:696\u0026ndash;704. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.ejim.2015.08.006\u003c/span\u003e\u003cspan address=\"10.1016/j.ejim.2015.08.006\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKiely DK, Jones RN, Bergmann MA, Marcantonio ER (2007) Association between psychomotor activity delirium subtypes and mortality among newly admitted post-acute facility patients. J Gerontol Biol Sci Med Sci 62:174\u0026ndash;179. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1093/gerona/62.2.174\u003c/span\u003e\u003cspan address=\"10.1093/gerona/62.2.174\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBellelli G, Carnevali L, Corsi M, Morandi A, Zambon A, Mazzola P et al (2018) The impact of psychomotor subtypes and duration of delirium on 6-month mortality in hip-fractured elderly patients. Int J Geriatr Psychiatry 33:1229\u0026ndash;1235. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/gps.4914\u003c/span\u003e\u003cspan address=\"10.1002/gps.4914\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFialho Silva IT, Assis Lopes P, Timotio Almeida T, Ramos SC, Caliman Fontes AT, Guimar\u0026atilde;es Silva D et al (2021) Impact of Delirium and Its Motor Subtypes on Stroke Outcomes. Stroke 52:1322\u0026ndash;1329. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1161/STROKEAHA.120.026425\u003c/span\u003e\u003cspan address=\"10.1161/STROKEAHA.120.026425\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGual N, Inzitari M, Carrizo G, Calle A, Udina C, Yuste A et al (2018) Delirium Subtypes and Associated Characteristics in Older Patients With Exacerbation of Chronic Conditions. Am J Geriatr Psychiatry Off J Am Assoc Geriatr Psychiatry 26:1204\u0026ndash;1212. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jagp.2018.07.003\u003c/span\u003e\u003cspan address=\"10.1016/j.jagp.2018.07.003\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMeagher DJ, Leonard M, Donnelly S, Conroy M, Adamis D, Trzepacz PT (2011) A longitudinal study of motor subtypes in delirium: relationship with other phenomenology, etiology, medication exposure and prognosis. J Psychosom Res 71:395\u0026ndash;403. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jpsychores.2011.06.001\u003c/span\u003e\u003cspan address=\"10.1016/j.jpsychores.2011.06.001\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRobinson TN, Raeburn CD, Tran ZV, Brenner LA, Moss M (2011) Motor subtypes of postoperative delirium in older adults. Arch Surg Chic Ill 1960 146:295\u0026ndash;300. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1001/archsurg.2011.14\u003c/span\u003e\u003cspan address=\"10.1001/archsurg.2011.14\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCunha AIL, Veronese N, de Melo Borges S, Ricci NA (2019) Frailty as a predictor of adverse outcomes in hospitalized older adults: A systematic review and meta-analysis. Ageing Res Rev 56:100960. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.arr.2019.100960\u003c/span\u003e\u003cspan address=\"10.1016/j.arr.2019.100960\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBellelli G, Triolo F, Ferrara MC, Deiner SG, Morandi A, Cesari M et al (2024) Delirium and frailty in older adults: Clinical overlap and biological underpinnings. J Intern Med 296:382\u0026ndash;398. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/joim.20014\u003c/span\u003e\u003cspan address=\"10.1111/joim.20014\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGhezzi ES, Greaves D, Boord MS, Davis D, Knayfati S, Astley JM et al (2022) How do predisposing factors differ between delirium motor subtypes? A systematic review and meta-analysis. Age Ageing 51:afac200. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1093/ageing/afac200\u003c/span\u003e\u003cspan address=\"10.1093/ageing/afac200\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOkoye C, Mazzarone T, Finazzi A, Daniela G, Bruni AA, Maccioni L et al (2025) Outcomes of early post-discharge cardio-geriatric care in frail patients after acute heart failure: a before-and-after study. BMC Geriatr 25:1\u0026ndash;10. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/s12877-025-05883-z\u003c/span\u003e\u003cspan address=\"10.1186/s12877-025-05883-z\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTesfaye Y, Davis CR, Hull MJ, Greaves D, du Preez J, Johns S et al (2025) Long-term clinical outcomes of delirium after hospital discharge: a systematic review and meta-analysis. Age Ageing 54:afaf188. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1093/ageing/afaf188\u003c/span\u003e\u003cspan address=\"10.1093/ageing/afaf188\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"european-geriatric-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"EGEM","sideBox":"Learn more about [European Geriatric Medicine](https://www.springer.com/journal/41999)","snPcode":"41999","submissionUrl":"https://www.editorialmanager.com/egem/default2.aspx","title":"European Geriatric Medicine","twitterHandle":"","acdcEnabled":false,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Acute Heart Failure, Delirium Subtypes, Older Adults, Mortality","lastPublishedDoi":"10.21203/rs.3.rs-7668204/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7668204/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePURPOSE\u003c/h2\u003e\u003cp\u003eDelirium is a common complication in older adults hospitalised for acute heart failure (AHF), but its incidence, subtypes, and short-term outcomes remain poorly characterised in the very old population. This study aimed to determine the prevalence and incidence of delirium in patients admitted to an acute geriatric unit (AGU) with AHF, to describe its subtypes, and to assess their impact on 90-day post-discharge survival.\u003c/p\u003e\u003ch2\u003eMETHODS\u003c/h2\u003e\u003cp\u003eThis prospective observational study included older adults hospitalised for AHF in an AGU between April 2022 and November 2024. Delirium was assessed using the 4AT and DSM-5 criteria and categorised as prevalent (on admission) or incident (during hospitalisation). Psychomotor delirium subtypes were classified as hyperactive, hypoactive, or mixed. Sociodemographic, clinical, and follow-up data were collected. Ninety-day survival was evaluated using Kaplan-Meier curves and Cox regression models.\u003c/p\u003e\u003ch2\u003eRESULTS\u003c/h2\u003e\u003cp\u003eAmong 399 patients (median age 87.4 years, 52% female), 132 (33%) experienced delirium, with 13.8% classified as prevalent and 19.2% as incident cases. Among those with delirium, 48% presented with the hyperactive, 31% with hypoactive, and 21% with the mixed subtype. In multivariable regression analysis, adjusted for relevant covariates, the hypoactive (adjusted HR 2.03, 95% CI 1.13\u0026ndash;3.64) and mixed (adjusted HR 2.28, 95% CI 1.18\u0026ndash;4.43) subtypes \u0026ndash;but not hyperactive\u0026ndash;were independently associated with an increased risk of death.\u003c/p\u003e\u003ch2\u003eCONCLUSIONS\u003c/h2\u003e\u003cp\u003eDelirium is common in very old patients hospitalised for AHF. The hypoactive and mixed subtypes are independently associated with poor 90-day post-discharge survival, highlighting the importance of their active identification and management.\u003c/p\u003e","manuscriptTitle":"Impact of Hypoactive and Mixed Delirium on Short-Term Survival in Older Adults Hospitalised for Acute Heart Failure: A Prospective Study in an Acute Geriatric Unit","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-15 02:20:49","doi":"10.21203/rs.3.rs-7668204/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revisions","date":"2025-11-30T15:04:38+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2025-10-06T07:20:20+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-30T11:58:09+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"European Geriatric Medicine","date":"2025-09-23T17:43:58+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-23T16:50:37+00:00","index":"","fulltext":""},{"type":"submitted","content":"European Geriatric Medicine","date":"2025-09-21T13:31:50+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"european-geriatric-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"EGEM","sideBox":"Learn more about [European Geriatric Medicine](https://www.springer.com/journal/41999)","snPcode":"41999","submissionUrl":"https://www.editorialmanager.com/egem/default2.aspx","title":"European Geriatric Medicine","twitterHandle":"","acdcEnabled":false,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"62f1b15d-3cff-440c-abc3-120f9c330de1","owner":[],"postedDate":"October 15th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-12-24T17:37:09+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-15 02:20:49","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7668204","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7668204","identity":"rs-7668204","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}