{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T01:25:14Z","timestamp":1792027514605,"version":"4.4.0"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,7]]},"abstract":"\n Objectives:<\/jats:title>\n To apply unsupervised clustering methods to hemodynamic and transthoracic echocardiography (TTE) parameters to identify cardiovascular subphenotypes in ICU patients with sepsis. To examine subphenotype association with mortality and determine how differing hemodynamic management strategies influence these associations.<\/jats:p>\n <\/jats:sec>\n \n Design:<\/jats:title>\n Retrospective, single-center cohort study.<\/jats:p>\n <\/jats:sec>\n \n Setting:<\/jats:title>\n University Hospital ICU, Birmingham, United Kingdom.<\/jats:p>\n <\/jats:sec>\n \n Patients:<\/jats:title>\n ICU patients that received TTE within 7 days of sepsis onset between April 2016 and December 2019 (derivation cohort) and January 2020 and December 2021 (validation cohort).<\/jats:p>\n <\/jats:sec>\n \n Interventions:<\/jats:title>\n None.<\/jats:p>\n <\/jats:sec>\n \n Measurements and Main Results:<\/jats:title>\n \n Nine hundred ninety-five patients were included in the derivation cohort and 804 patients in the validation cohort. A four-class model best fit both cohorts: class 1 (51% in derivation cohort, 56% in validation cohort; mostly normal left ventricular [LV] and right ventricular [RV] function), class 2 (30% in derivation cohort, 22% in validation cohort; mostly high cardiac index, hyperdynamic LV ejection fraction), class 3 (10% in derivation cohort, 12% in validation cohort, mostly dilated RV with impaired systolic function), and class 4 (9% in derivation cohort, 10% in validation cohort; mostly low cardiac output, with depressed LV ejection fraction). The four subphenotypes differed in their characteristics and outcomes, with 90-day mortality rates of classes 1\u20134 of 20%, 46%, 47%, and 41% in the derivation cohort and 18%, 45%, 57%, and 58% in the validation cohort, respectively (\n p<\/jats:italic>\n < 0.0001 for both cohorts). Following multivariable logistic regression analysis, classes 2\u20134 were independently associated with mortality. Three-variable models had high diagnostic accuracy in identifying all subphenotypes in both cohorts. The association with mortality of classes varied according to differing vasoactive agent and fluid administration strategies.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n Clustering analysis identified four cardiovascular subphenotypes in sepsis that reflected distinct circulatory failure mechanisms, were identifiable using simple models, and were associated with differing mortality risks and response to hemodynamic therapies. These classes may represent treatable traits to personalize shock management in sepsis.<\/jats:p>\n <\/jats:sec>","DOI":"10.1097\/ccm.0000000000007159","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T14:27:18Z","timestamp":1779805638000},"page":"1622-1634","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":2,"title":["Cardiovascular Subphenotypes in Sepsis"],"prefix":"10.1097","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2206-1678","authenticated-orcid":false,"given":"Minesh","family":"Chotalia","sequence":"first","affiliation":[{"name":"Birmingham Acute Care Research Group, Department of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom."},{"name":"Department of Anaesthetics and Critical Care, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muzzammil","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Anaesthetics and Critical Care, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi","family":"Chotalia","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Lincoln County Hospital, Lincoln, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaimin M.","family":"Patel","sequence":"additional","affiliation":[{"name":"Birmingham Acute Care Research Group, Department of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom."},{"name":"Department of Anaesthetics and Critical Care, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhruv","family":"Parekh","sequence":"additional","affiliation":[{"name":"Birmingham Acute Care Research Group, Department of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom."},{"name":"Department of Anaesthetics and Critical Care, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mansoor N.","family":"Bangash","sequence":"additional","affiliation":[{"name":"Birmingham Acute Care Research Group, Department of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom."},{"name":"Department of Anaesthetics and Critical Care, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"R1-20260713","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, regional, and national sepsis incidence and mortality, 1990\u20132017: Analysis for the Global Burden of Disease Study.","volume":"395","author":"Rudd","year":"2020","journal-title":"Lancet"},{"key":"R2-20260713","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1164\/rccm.201504-0781OC","article-title":"Assessment of global incidence and mortality of hospital-treated sepsis. Current estimates and limitations.","volume":"193","author":"Fleischmann","year":"2016","journal-title":"Am J Respir Crit Care Med"},{"key":"R3-20260713","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.jcrc.2016.11.036","article-title":"Reasons for death in patients with sepsis and septic shock.","volume":"38","author":"Moskowitz","year":"2017","journal-title":"J Crit Care"},{"key":"R4-20260713","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1097\/CCM.0000000000006135","article-title":"Surviving sepsis campaign research priorities 2023.","volume":"52","author":"De Backer","year":"2024","journal-title":"Crit Care Med"},{"key":"R5-20260713","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1007\/s00134-021-06506-y","article-title":"Surviving sepsis campaign: International guidelines for management of sepsis and septic shock 2021.","volume":"47","author":"Evans","year":"2021","journal-title":"Intensive Care Med"},{"key":"R6-20260713","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1016\/j.chest.2023.01.010","article-title":"Is left ventricular systolic dysfunction associated with increased mortality among patients with sepsis and septic shock?","volume":"163","author":"Dugar","year":"2023","journal-title":"Chest"},{"key":"R7-20260713","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1097\/CCM.0000000000005315","article-title":"Hyperdynamic left ventricular ejection fraction in ICU patients with sepsis.","volume":"50","author":"Chotalia","year":"2022","journal-title":"Crit Care Med"},{"key":"R8-20260713","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s13613-024-01255-9","article-title":"Prevalence and prognosis of hyperdynamic left ventricular systolic function in septic patients: A systematic review and meta-analysis.","volume":"14","author":"Sato","year":"2024","journal-title":"Ann Intensive Care"},{"key":"R9-20260713","doi-asserted-by":"crossref","first-page":"100767","DOI":"10.1016\/j.cpcardiol.2020.100767","article-title":"Septic cardiomyopathy: From basics to management choices.","volume":"46","author":"Ravikumar","year":"2021","journal-title":"Curr Probl Cardiol"},{"key":"R10-20260713","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1097\/CCM.0000000000002851","article-title":"Septic cardiomyopathy.","volume":"46","author":"Beesley","year":"2018","journal-title":"Crit Care Med"},{"key":"R11-20260713","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1093\/eurheartj\/ehr351","article-title":"Diastolic dysfunction and mortality in severe sepsis and septic shock.","volume":"33","author":"Landesberg","year":"2012","journal-title":"Eur Heart J"},{"key":"R12-20260713","doi-asserted-by":"crossref","first-page":"2254","DOI":"10.1016\/j.chest.2020.12.016","article-title":"Impact of right ventricular dysfunction on short-term and long-term mortality in sepsis.","volume":"159","author":"Vallabhajosyula","year":"2021","journal-title":"Chest"},{"key":"R13-20260713","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1056\/NEJMclde1815472","article-title":"Sepsis guidelines.","volume":"380","author":"Chen","year":"2019","journal-title":"N Engl J Med"},{"key":"R14-20260713","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.amjcard.2022.10.029","article-title":"Echocardiographic characteristics and clinical outcomes of the hyperdynamic heart: A \u201cSuper-Normal\u201d heart is not a normal heart.","volume":"187","author":"Gotsman","year":"2023","journal-title":"Am J Cardiol"},{"key":"R15-20260713","doi-asserted-by":"crossref","first-page":"e263","DOI":"10.1016\/j.chest.2019.11.060","article-title":"A hyperdynamic left ventricle on echocardiogram.","volume":"158","author":"Singer","year":"2020","journal-title":"Chest"},{"key":"R16-20260713","doi-asserted-by":"crossref","first-page":"e63","DOI":"10.1097\/CCM.0000000000004710","article-title":"Practitioner\u2019s guide to latent class analysis: Methodological considerations and common pitfalls.","volume":"49","author":"Sinha","year":"2021","journal-title":"Crit Care Med"},{"key":"R17-20260713","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1001\/jama.2019.5791","article-title":"Derivation, validation, and potential treatment implications of novel clinical phenotypes for sepsis.","volume":"321","author":"Seymour","year":"2019","journal-title":"JAMA"},{"key":"R18-20260713","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1007\/s00134-022-06890-z","article-title":"Development and validation of novel sepsis subphenotypes using trajectories of vital signs.","volume":"48","author":"Bhavani","year":"2022","journal-title":"Intensive Care Med"},{"key":"R19-20260713","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/S2213-2600(23)00237-0","article-title":"Identifying molecular phenotypes in sepsis: An analysis of two prospective observational cohorts and secondary analysis of two randomised controlled trials.","volume":"11","author":"Sinha","year":"2023","journal-title":"Lancet Respir Med"},{"key":"R20-20260713","doi-asserted-by":"crossref","first-page":"2094","DOI":"10.1007\/s00134-024-07669-0","article-title":"Distinct immune profiles and clinical outcomes in sepsis subphenotypes based on temperature trajectories.","volume":"50","author":"Bhavani","year":"2024","journal-title":"Intensive Care Med"},{"key":"R21-20260713","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1186\/s13054-015-1026-2","article-title":"Development of metabolic and inflammatory mediator biomarker phenotyping for early diagnosis and triage of pediatric sepsis.","volume":"19","author":"Mickiewicz","year":"2015","journal-title":"Crit Care"},{"key":"R22-20260713","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1164\/rccm.201807-1419OC","article-title":"Transcriptomic signatures in sepsis and a differential response to steroids. From the VANISH randomized trial.","volume":"199","author":"Antcliffe","year":"2019","journal-title":"Am J Respir Crit Care Med"},{"key":"R23-20260713","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1097\/CCM.0000000000003084","article-title":"Unsupervised analysis of transcriptomics in bacterial sepsis across multiple datasets reveals three robust clusters.","volume":"46","author":"Sweeney","year":"2018","journal-title":"Crit Care Med"},{"key":"R24-20260713","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1007\/s00134-019-05596-z","article-title":"Cardiovascular clusters in septic shock combining clinical and echocardiographic parameters: A post hoc analysis.","volume":"45","author":"Geri","year":"2019","journal-title":"Intensive Care Med"},{"key":"R25-20260713","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1111\/anae.15700","article-title":"Cardiovascular subphenotypes in patients with COVID-19 pneumonitis whose lungs are mechanically ventilated: A single-centre retrospective observational study.","volume":"77","author":"Chotalia","year":"2022","journal-title":"Anaesthesia"},{"key":"R26-20260713","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1097\/CCM.0000000000005751","article-title":"Cardiovascular subphenotypes in acute respiratory distress syndrome.","volume":"51","author":"Chotalia","year":"2023","journal-title":"Crit Care Med"},{"key":"R27-20260713","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1038\/s41591-022-01843-x","article-title":"Redefining critical illness.","volume":"28","author":"Maslove","year":"2022","journal-title":"Nat Med"},{"key":"R28-20260713","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The third international consensus definitions for sepsis and septic shock (Sepsis-3).","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"R29-20260713","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1097\/CCM.0000000000005167","article-title":"Right ventricular dysfunction and its association with mortality in coronavirus disease 2019 acute respiratory distress syndrome*.","volume":"49","author":"Chotalia","year":"2021","journal-title":"Crit Care Med"},{"key":"R30-20260713","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1111\/anae.15453","article-title":"A time-sensitive analysis of the prognostic utility of vasopressor dose in septic shock.","volume":"76","author":"Chotalia","year":"2021","journal-title":"Anaesthesia"},{"key":"R31-20260713","doi-asserted-by":"crossref","first-page":"e1063","DOI":"10.1097\/CCM.0000000000005337","article-title":"Surviving sepsis campaign: International guidelines for management of sepsis and septic shock 2021.","volume":"49","author":"Evans","year":"2021","journal-title":"Crit Care Med"},{"key":"R32-20260713","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1186\/s13054-018-2102-1","article-title":"Definitions and pathophysiology of vasoplegic shock.","volume":"22","author":"Lambden","year":"2018","journal-title":"Crit Care"},{"key":"R33-20260713","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1016\/j.jhep.2014.05.047","article-title":"Vascular pathobiology in chronic liver disease and cirrhosis\u2014current status and future directions.","volume":"61","author":"Iwakiri","year":"2014","journal-title":"J Hepatol"},{"key":"R35-20260713","doi-asserted-by":"crossref","first-page":"e0218624","DOI":"10.1371\/journal.pone.0218624","article-title":"Sepsis causes right ventricular myocardial inflammation independent of pulmonary hypertension in a porcine sepsis model.","volume":"14","author":"Pischke","year":"2019","journal-title":"PLoS One"},{"key":"R36-20260713","doi-asserted-by":"crossref","first-page":"1200441","DOI":"10.3389\/fcvm.2023.1200441","article-title":"Sepsis-Induced myocardial dysfunction: Heterogeneity of functional effects and clinical significance.","volume":"10","author":"Shvilkina","year":"2023","journal-title":"Front Cardiovasc Med"},{"key":"R37-20260713","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1001\/jama.2016.10485","article-title":"Effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock: The VANISH randomized clinical trial.","volume":"316","author":"Gordon","year":"2016","journal-title":"JAMA"},{"key":"R38-20260713","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1056\/NEJMoa067373","article-title":"Vasopressin versus norepinephrine infusion in patients with septic shock.","volume":"358","author":"Russell","year":"2008","journal-title":"N Engl J Med"},{"key":"R39-20260713","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3310\/eme05060","article-title":"Levosimendan to prevent acute organ dysfunction in sepsis: The LeoPARDS RCT.","volume":"5","author":"Gordon","year":"2018","journal-title":"Effic Mech Eval"},{"key":"R40-20260713","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1001\/jama.2017.9973","article-title":"Effect of levosimendan on low cardiac output syndrome in patients with low ejection fraction undergoing coronary artery bypass grafting with cardiopulmonary bypass: The LICORN randomized clinical trial.","volume":"318","author":"Cholley","year":"2017","journal-title":"JAMA"},{"key":"R41-20260713","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1007\/s00134-013-2982-0","article-title":"Effects of dobutamine on systemic, regional and microcirculatory perfusion parameters in septic shock: A randomized, placebo-controlled, double-blind, crossover study.","volume":"39","author":"Hernandez","year":"2013","journal-title":"Intensive Care Med"},{"key":"R42-20260713","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1007\/s00134-019-05631-z","article-title":"The use of clustering algorithms in critical care research to unravel patient heterogeneity.","volume":"45","author":"Castela Forte","year":"2019","journal-title":"Intensive Care Med"}],"container-title":["Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/10.1097\/CCM.0000000000007159","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T16:00:19Z","timestamp":1783958419000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/10.1097\/CCM.0000000000007159"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,26]]},"references-count":41,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.1097\/ccm.0000000000007159","relation":{},"ISSN":["0090-3493","1530-0293"],"issn-type":[{"value":"0090-3493","type":"print"},{"value":"1530-0293","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,26]]}}}