{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T16:45:47Z","timestamp":1754153147207,"version":"3.41.2"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T00:00:00Z","timestamp":1745971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010447","name":"German Centre for Cardiovascular Research","doi-asserted-by":"publisher","award":["81Z0600209"],"award-info":[{"award-number":["81Z0600209"]}],"id":[{"id":"10.13039\/100010447","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ludwig Maximilian University"},{"name":"University Hospital Munich"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Treatment capacities on intensive care units (ICUs) are a limited resource reserved for high-risk patients. To facilitate risk stratification of ICU patients, several scoring systems have been developed over time. Among them, the Simplified Acute Physiology Score 3 (SAPS3) is the gold standard, but lacks specificity for cardiac ICU patients. Here, we propose a novel, fully automated, electrocardiogram-based cardiac autonomic risk stratification score (CAFICU) that substantially adds to current risk stratification strategies.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>CAFICU is based on periodic repolarization dynamics, a marker of sympathetic overactivity and deceleration capacity of heart rate, a parameter of vagal imbalance. We developed CAFICU in a retrospective cohort of 355 ICU patients and subsequently validated the score in a cohort of 702 ICU patients, enrolled between February\u2013November 2018 and December 2018\u2013April 2020 at a large cardiac ICU in a tertiary hospital. The primary endpoint of the study was 30-day intrahospital mortality. Thirty (8.5%) and 100 (14.2%) patients reached the primary endpoint in the training and validation cohorts, respectively. CAFICU was significantly higher in non-survivors than survivors (2.58 \u00b1 1.34 vs. 1.76 \u00b1 0.97 units; P = 0.003 in the training cohort and 2.20 \u00b1 1.05 vs. 1.70 \u00b1 0.83 units; P &amp;lt; 0.001 in the validation cohort) and was a strong predictor of mortality in both the training [hazard ratio (HR) 25.67; 95% confidence interval (CI) 3.50\u2013188.40; P = 0.001] and validation cohorts (HR 4.70; 95% CI 2.79\u20137.92; P &amp;lt; 0.001). In the pooled cohort, CAFICU significantly improved risk stratification based on SAPS3 (IDI-increase 0.033; 95% CI 0.010\u20130.061; P &amp;lt; 0.001).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>ECG-based automatic autonomic risk stratification by means of PRD and DC is highly predictive of short-term mortality in the ICU and can be combined with the SAPS3-Score to identify patients with increased risk for intrahospital mortality. This method can be integrated in conventional monitors and may improve risk stratification strategies in cardiac ICUs.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ehjdh\/ztaf038","type":"journal-article","created":{"date-parts":[[2025,4,30]],"date-time":"2025-04-30T23:41:58Z","timestamp":1746056518000},"page":"822-832","source":"Crossref","is-referenced-by-count":0,"title":["Cardiac autonomic function score: a novel risk stratification tool in the cardiac intensive care unit based on periodic repolarization dynamics and deceleration capacity of heart rate (LMU-eICU study)"],"prefix":"10.1093","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4617-3446","authenticated-orcid":false,"given":"Mathias","family":"Klemm","sequence":"first","affiliation":[{"name":"Medizinische Klinik und Poliklinik I, LMU Klinikum, Ludwigs-Maximilians-University Munich , Ziemsenstr. 5, 80336 Munich ,","place":["Germany"]},{"name":"German Centre for Cardiovascular Research (DZHK) , Partner Site Munich Heart Alliance, Pettekoferstr. 9, 80336 Munich ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2238-2815","authenticated-orcid":false,"given":"Lukas","family":"von St\u00fclpnagel","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik I, LMU Klinikum, Ludwigs-Maximilians-University Munich , Ziemsenstr. 5, 80336 Munich ,","place":["Germany"]},{"name":"German Centre for Cardiovascular Research (DZHK) , Partner Site Munich Heart Alliance, Pettekoferstr. 9, 80336 Munich ,","place":["Germany"]},{"name":"University Hospital for Internal Medicine III, Medical University of Innsbruck , Anichstr. 35, 6020 Innsbruck ,","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentin","family":"Ostermaier","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik I, LMU Klinikum, Ludwigs-Maximilians-University Munich , Ziemsenstr. 5, 80336 Munich ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carsten","family":"Theurer","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik I, LMU Klinikum, Ludwigs-Maximilians-University Munich , Ziemsenstr. 5, 80336 Munich ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura E","family":"Villegas Sierra","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik I, LMU Klinikum, Ludwigs-Maximilians-University Munich , Ziemsenstr. 5, 80336 Munich ,","place":["Germany"]},{"name":"German Centre for Cardiovascular Research (DZHK) , Partner Site Munich Heart Alliance, Pettekoferstr. 9, 80336 Munich ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felix","family":"Wenner","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik I, LMU Klinikum, Ludwigs-Maximilians-University Munich , Ziemsenstr. 5, 80336 Munich ,","place":["Germany"]},{"name":"German Centre for Cardiovascular Research (DZHK) , Partner Site Munich Heart Alliance, Pettekoferstr. 9, 80336 Munich ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5971-4903","authenticated-orcid":false,"given":"Elodie","family":"Eiffener","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik I, LMU Klinikum, Ludwigs-Maximilians-University Munich , Ziemsenstr. 5, 80336 Munich ,","place":["Germany"]},{"name":"German Centre for Cardiovascular Research (DZHK) , Partner Site Munich Heart Alliance, Pettekoferstr. 9, 80336 Munich ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aresa","family":"Krasniqi","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik I, LMU Klinikum, Ludwigs-Maximilians-University Munich , Ziemsenstr. 5, 80336 Munich ,","place":["Germany"]},{"name":"German Centre for Cardiovascular Research (DZHK) , Partner Site Munich Heart Alliance, Pettekoferstr. 9, 80336 Munich ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8702-7369","authenticated-orcid":false,"given":"Konstantinos","family":"Mourouzis","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik I, LMU Klinikum, Ludwigs-Maximilians-University Munich , Ziemsenstr. 5, 80336 Munich ,","place":["Germany"]},{"name":"German Centre for Cardiovascular Research (DZHK) , Partner Site Munich Heart Alliance, Pettekoferstr. 9, 80336 Munich ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7736-9445","authenticated-orcid":false,"given":"Lauren E","family":"Sams","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik I, LMU Klinikum, Ludwigs-Maximilians-University Munich , Ziemsenstr. 5, 80336 Munich ,","place":["Germany"]},{"name":"German Centre for Cardiovascular Research (DZHK) , Partner Site Munich Heart Alliance, Pettekoferstr. 9, 80336 Munich ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6302-8266","authenticated-orcid":false,"given":"Luisa","family":"Freyer","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik I, LMU Klinikum, Ludwigs-Maximilians-University Munich , Ziemsenstr. 5, 80336 Munich ,","place":["Germany"]},{"name":"German Centre for Cardiovascular Research (DZHK) , Partner Site Munich Heart Alliance, Pettekoferstr. 9, 80336 Munich ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7387-3986","authenticated-orcid":false,"given":"Steffen","family":"Massberg","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik I, LMU Klinikum, Ludwigs-Maximilians-University Munich , Ziemsenstr. 5, 80336 Munich ,","place":["Germany"]},{"name":"German Centre for Cardiovascular Research (DZHK) , Partner Site Munich Heart Alliance, Pettekoferstr. 9, 80336 Munich ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Axel","family":"Bauer","sequence":"additional","affiliation":[{"name":"University Hospital for Internal Medicine III, Medical University of Innsbruck , Anichstr. 35, 6020 Innsbruck ,","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5993-0339","authenticated-orcid":false,"given":"Konstantinos D","family":"Rizas","sequence":"additional","affiliation":[{"name":"Medizinische Klinik und Poliklinik I, LMU Klinikum, Ludwigs-Maximilians-University Munich , Ziemsenstr. 5, 80336 Munich ,","place":["Germany"]},{"name":"German Centre for Cardiovascular Research (DZHK) , Partner Site Munich Heart Alliance, Pettekoferstr. 9, 80336 Munich ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,4,30]]},"reference":[{"key":"2025072210473639500_ztaf038-B1","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1007\/BF01709751","article-title":"The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction\/failure","volume":"22","author":"Vincent","year":"1996","journal-title":"Intensive Care Med"},{"key":"2025072210473639500_ztaf038-B2","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1007\/s00134-005-2763-5","article-title":"SAPS 3\u2014from evaluation of the patient to evaluation of the intensive care unit. Part 2: Development of a prognostic model for hospital mortality at ICU admission","volume":"31","author":"Moreno","year":"2005","journal-title":"Intensive Care Med"},{"key":"2025072210473639500_ztaf038-B3","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1097\/01.CCM.0000257337.63529.9F","article-title":"Assessing contemporary intensive care unit outcome: an updated Mortality Probability Admission Model (MPM0-III)","volume":"35","author":"Higgins","year":"2007","journal-title":"Crit Care Med"},{"key":"2025072210473639500_ztaf038-B4","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1097\/00003246-198510000-00009","article-title":"APACHE II: a severity of disease classification system","volume":"13","author":"Knaus","year":"1985","journal-title":"Crit Care Med"},{"key":"2025072210473639500_ztaf038-B5","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1093\/oxfordjournals.eurheartj.a014868","article-title":"Heart rate variability. Standards of measurement, physiological interpretation, and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology","volume":"17","author":"Malik","year":"1996","journal-title":"Eur Heart J"},{"key":"2025072210473639500_ztaf038-B6","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1161\/CIRCULATIONAHA.121.056464","article-title":"Periodic repolarization dynamics identifies ICD responders in nonischemic cardiomyopathy: a DANISH substudy","volume":"145","author":"Boas","year":"2022","journal-title":"Circulation"},{"key":"2025072210473639500_ztaf038-B7","doi-asserted-by":"crossref","first-page":"2110","DOI":"10.1093\/eurheartj\/ehx161","article-title":"Prediction of sudden and non-sudden cardiac death in post-infarction patients with reduced left ventricular ejection fraction by periodic repolarization dynamics: MADIT-II substudy","volume":"38","author":"Rizas","year":"2017","journal-title":"Eur Heart J"},{"key":"2025072210473639500_ztaf038-B8","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1172\/JCI70085","article-title":"Sympathetic activity-associated periodic repolarization dynamics predict mortality following myocardial infarction","volume":"124","author":"Rizas","year":"2014","journal-title":"J Clin Invest"},{"key":"2025072210473639500_ztaf038-B9","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1016\/S0140-6736(06)68735-7","article-title":"Deceleration capacity of heart rate as a predictor of mortality after myocardial infarction: cohort study","volume":"367","author":"Bauer","year":"2006","journal-title":"Lancet"},{"key":"2025072210473639500_ztaf038-B10","doi-asserted-by":"crossref","first-page":"f129","DOI":"10.1093\/europace\/eux167","article-title":"Bedside autonomic risk stratification after myocardial infarction by means of short-term deceleration capacity of heart rate","volume":"20","author":"Rizas","year":"2018","journal-title":"Europace"},{"key":"2025072210473639500_ztaf038-B11","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1109\/TBME.1985.325532","article-title":"A real-time QRS detection algorithm","volume":"32","author":"Pan","year":"1985","journal-title":"IEEE Trans Biomed Eng"},{"key":"2025072210473639500_ztaf038-B12","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1016\/j.amjcard.2011.01.028","article-title":"A simple method to detect atrial fibrillation using RR intervals","volume":"107","author":"Lian","year":"2011","journal-title":"Am J Cardiol"},{"key":"2025072210473639500_ztaf038-B13","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1111\/anec.12107","article-title":"Automated assessment of cardiac autonomic function by means of deceleration capacity from noisy, nonstationary ECG signals: validation study","volume":"19","author":"Eick","year":"2014","journal-title":"Ann Noninvasive Electrocardiol"},{"key":"2025072210473639500_ztaf038-B14","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1097\/CCM.0000000000000922","article-title":"Autonomic nervous system activity as risk predictor in the medical emergency department: a prospective cohort study","volume":"43","author":"Eick","year":"2015","journal-title":"Crit Care Med"},{"key":"2025072210473639500_ztaf038-B15","doi-asserted-by":"crossref","first-page":"e105","DOI":"10.1016\/S2589-7500(21)00253-3","article-title":"Telemedical cardiac risk assessment by implantable cardiac monitors in patients after myocardial infarction with autonomic dysfunction (SMART-MI-DZHK9): a prospective investigator-initiated, randomised, multicentre, open-label, diagnostic trial","volume":"4","author":"Bauer","year":"2022","journal-title":"Lancet Digit Health"},{"key":"2025072210473639500_ztaf038-B16","first-page":"29","article-title":"SCAI clinical expert consensus statement on the classification of cardiogenic shock","volume":"94","author":"Baran","year":"2019","journal-title":"Catheter Cardiovasc Interv"},{"key":"2025072210473639500_ztaf038-B17","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1016\/S0895-4356(96)00236-3","article-title":"A simulation study of the number of events per variable in logistic regression analysis","volume":"49","author":"Peduzzi","year":"1996","journal-title":"J Clin Epidemiol"},{"key":"2025072210473639500_ztaf038-B18","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1002\/sim.4085","article-title":"Extensions of net reclassification improvement calculations to measure usefulness of new biomarkers","volume":"30","author":"Pencina","year":"2011","journal-title":"Stat Med"},{"key":"2025072210473639500_ztaf038-B19","first-page":"5","article-title":"An introduction to recursive partitioning using the RPART routines","volume":"61","author":"Therneau","year":"1997","journal-title":"Mayo Clinic"},{"key":"2025072210473639500_ztaf038-B20","doi-asserted-by":"crossref","first-page":"28","DOI":"10.18637\/jss.v042.i08","article-title":"Matchit: nonparametric preprocessing for parametric causal inference (version 2.211) [software]","volume":"42","author":"Ho","year":"2011","journal-title":"J Stat Softw"},{"key":"2025072210473639500_ztaf038-B21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v045.i07","article-title":"AMELIA II: a program for missing data","volume":"45","author":"Honaker","year":"2011","journal-title":"J Stat Softw"},{"key":"2025072210473639500_ztaf038-B22","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/s13756-018-0370-9","article-title":"Risk factors for hospitalized patients with resistant or multidrug-resistant Pseudomonas aeruginosa infections: a systematic review and meta-analysis","volume":"7","author":"Raman","year":"2018","journal-title":"Antimicrob Resist Infect Control"},{"key":"2025072210473639500_ztaf038-B23","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1002\/ams2.415","article-title":"Post-intensive care syndrome: its pathophysiology, prevention, and future directions","volume":"6","author":"Inoue","year":"2019","journal-title":"Acute Med Surg"},{"key":"2025072210473639500_ztaf038-B24","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1056\/NEJMoa2307227","article-title":"Extracorporeal life support in infarct-related cardiogenic shock","volume":"389","author":"Thiele","year":"2023","journal-title":"N Engl J Med"},{"key":"2025072210473639500_ztaf038-B25","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s13613-019-0488-9","article-title":"The prognostic accuracy evaluation of SAPS 3, SOFA and APACHE II scores for mortality prediction in the surgical ICU: an external validation study and decision-making analysis","volume":"9","author":"Falc\u00e3o","year":"2019","journal-title":"Ann Intensive Care"},{"key":"2025072210473639500_ztaf038-B26","doi-asserted-by":"crossref","first-page":"989561","DOI":"10.3389\/fcvm.2022.989561","article-title":"Simplified acute physiology score III is excellent for predicting in-hospital mortality in coronary care unit patients with acute myocardial infarction: a retrospective study","volume":"9","author":"Zheng","year":"2022","journal-title":"Front Cardiovasc Med"},{"key":"2025072210473639500_ztaf038-B27","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1097\/CCM.0b013e318270e6f0","article-title":"Challenges of heart rate variability research in the ICU","volume":"41","author":"Stein","year":"2013","journal-title":"Crit Care Med"},{"key":"2025072210473639500_ztaf038-B28","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1016\/S0140-6736(19)31996-8","article-title":"Prediction of mortality benefit based on periodic repolarisation dynamics in patients undergoing prophylactic implantation of a defibrillator: a prospective, controlled, multicentre cohort study","volume":"394","author":"Bauer","year":"2019","journal-title":"Lancet"},{"key":"2025072210473639500_ztaf038-B29","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/S0002-8703(99)70507-7","article-title":"Weekly and seasonal variation in the incidence of cardiac arrests","volume":"137","author":"Peckova","year":"1999","journal-title":"Am Heart J"},{"key":"2025072210473639500_ztaf038-B30","doi-asserted-by":"crossref","first-page":"e008169","DOI":"10.1161\/JAHA.117.008169","article-title":"Predictive value of the Sequential Organ Failure Assessment score for mortality in a contemporary cardiac intensive care unit population","volume":"7","author":"Jentzer","year":"2018","journal-title":"J Am Heart Assoc"},{"key":"2025072210473639500_ztaf038-B31","doi-asserted-by":"crossref","first-page":"e013675","DOI":"10.1161\/JAHA.119.013675","article-title":"Derivation and validation of a novel cardiac intensive care unit admission risk score for mortality","volume":"8","author":"Jentzer","year":"2019","journal-title":"J Am Heart Assoc"}],"container-title":["European Heart Journal - Digital Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ehjdh\/advance-article-pdf\/doi\/10.1093\/ehjdh\/ztaf038\/63035507\/ztaf038.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ehjdh\/article-pdf\/6\/4\/822\/63035507\/ztaf038.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ehjdh\/article-pdf\/6\/4\/822\/63035507\/ztaf038.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T14:47:49Z","timestamp":1753195669000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ehjdh\/article\/6\/4\/822\/8123155"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,30]]},"references-count":31,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4,30]]},"published-print":{"date-parts":[[2025,7,22]]}},"URL":"https:\/\/doi.org\/10.1093\/ehjdh\/ztaf038","relation":{},"ISSN":["2634-3916"],"issn-type":[{"type":"electronic","value":"2634-3916"}],"subject":[],"published-other":{"date-parts":[[2025,7]]},"published":{"date-parts":[[2025,4,30]]}}}