title: Spectral analysis-based risk score enables early prediction of mortality and cerebral performance in patients undergoing therapeutic hypothermia for ventricular fibrillation and comatose status.
abstract: BACKGROUND
  Early prognosis in comatose survivors after cardiac arrest due to ventricular fibrillation (VF) is unreliable, especially in patients undergoing mild hypothermia. We aimed at developing a reliable risk-score to enable early prediction of cerebral performance and survival.
  
  
  METHODS
  Sixty-one out of 239 consecutive patients undergoing mild hypothermia after cardiac arrest, with eventual return of spontaneous circulation (ROSC), and comatose status on admission fulfilled the inclusion criteria. Background clinical variables, VF time and frequency domain fundamental variables were considered. The primary and secondary outcomes were a favorable neurological performance (FNP) during hospitalization and survival to hospital discharge, respectively. The predictive model was developed in a retrospective cohort (n = 32; September 2006-September 2011, 48.5 ± 10.5 months of follow-up) and further validated in a prospective cohort (n = 29; October 2011-July 2013, 5 ± 1.8 months of follow-up).
  
  
  RESULTS
  FNP was present in 16 (50.0%) and 21 patients (72.4%) in the retrospective and prospective cohorts, respectively. Seventeen (53.1%) and 21 patients (72.4%), respectively, survived to hospital discharge. Both outcomes were significantly associated (p < 0.001). Retrospective multivariate analysis provided a prediction model (sensitivity = 0.94, specificity = 1) that included spectral dominant frequency, derived power density and peak ratios between high and low frequency bands, and the number of shocks delivered before ROSC. Validation on the prospective cohort showed sensitivity = 0.88 and specificity = 0.91. A model-derived risk-score properly predicted 93% of FNP. Testing the model on follow-up showed a c-statistic ≥ 0.89.
  
  
  CONCLUSIONS
  A spectral analysis-based model reliably correlates time-dependent VF spectral changes with acute cerebral injury in comatose survivors undergoing mild hypothermia after cardiac arrest.
authors.affiliation: Atherothrombosis, Imaging and Epidemiology Department, Fundación Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain; Hospital Clínico San Carlos, Madrid, Spain; Hospital Universitario La Paz, IdiPaz, Madrid, Spain. Electronic address: david.filgueiras@cnic.es.
authors.forename: David
authors.initials: D
authors.lastname: Filgueiras-Rama
authors.affiliation: Bio-ITACA Grupo de Bioingeniería, Instituto de Aplicaciones Avanzadas, Dpto Ingeniería Electrónica, Universitat Politècnica de Valencia, Spain; Grupo Electrofisiología y Bioingeniería, Microcluster en Protección Cardiovascular, Dpto de Medicina, Fundación INCLIVA Hospital Clínico, Valencia, Spain.
authors.forename: Conrado J
authors.initials: CJ
authors.lastname: Calvo
authors.affiliation: Hospital Universitario La Paz, IdiPaz, Madrid, Spain.
authors.forename: Óscar
authors.initials: Ó
authors.lastname: Salvador-Montañés
authors.affiliation: Hospital Universitario La Paz, IdiPaz, Madrid, Spain.
authors.forename: Rosalía
authors.initials: R
authors.lastname: Cádenas
authors.affiliation: Hospital Universitario La Paz, IdiPaz, Madrid, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Ruiz-Cantador
authors.affiliation: Hospital Universitario La Paz, IdiPaz, Madrid, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Armada
authors.affiliation: Hospital Universitario La Paz, IdiPaz, Madrid, Spain.
authors.forename: Juan Ramón
authors.initials: JR
authors.lastname: Rey
authors.affiliation: Hospital Universitario La Paz, IdiPaz, Madrid, Spain.
authors.forename: J L
authors.initials: JL
authors.lastname: Merino
authors.affiliation: Hospital Universitario La Paz, IdiPaz, Madrid, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Peinado
authors.affiliation: Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Nicasio
authors.initials: N
authors.lastname: Pérez-Castellano
authors.affiliation: Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Julián
authors.initials: J
authors.lastname: Pérez-Villacastín
authors.affiliation: Atherothrombosis, Imaging and Epidemiology Department, Fundación Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
authors.forename: Jorge G
authors.initials: JG
authors.lastname: Quintanilla
authors.affiliation: Bio-ITACA Grupo de Bioingeniería, Instituto de Aplicaciones Avanzadas, Dpto Ingeniería Electrónica, Universitat Politècnica de Valencia, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Jiménez
authors.affiliation: Bio-ITACA Grupo de Bioingeniería, Instituto de Aplicaciones Avanzadas, Dpto Ingeniería Electrónica, Universitat Politècnica de Valencia, Spain; Grupo Electrofisiología y Bioingeniería, Microcluster en Protección Cardiovascular, Dpto de Medicina, Fundación INCLIVA Hospital Clínico, Valencia, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Castells
authors.affiliation: Grupo Electrofisiología y Bioingeniería, Microcluster en Protección Cardiovascular, Dpto de Medicina, Fundación INCLIVA Hospital Clínico, Valencia, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Chorro
authors.affiliation: Hospital Universitario La Paz, IdiPaz, Madrid, Spain.
authors.forename: J L
authors.initials: JL
authors.lastname: López-Sendón
authors.affiliation: Center for Arrhythmia Research, Cardiovascular Research Center, Department of Internal Medicine, University of MI, Ann Arbor, USA.
authors.forename: Omer
authors.initials: O
authors.lastname: Berenfeld
authors.affiliation: Atherothrombosis, Imaging and Epidemiology Department, Fundación Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain; Center for Arrhythmia Research, Cardiovascular Research Center, Department of Internal Medicine, University of MI, Ann Arbor, USA.
authors.forename: José
authors.initials: J
authors.lastname: Jalife
authors.affiliation: Hospital Universitario La Paz, IdiPaz, Madrid, Spain.
authors.forename: Esteban
authors.initials: E
authors.lastname: López de Sá
authors.affiliation: Bio-ITACA Grupo de Bioingeniería, Instituto de Aplicaciones Avanzadas, Dpto Ingeniería Electrónica, Universitat Politècnica de Valencia, Spain; Grupo Electrofisiología y Bioingeniería, Microcluster en Protección Cardiovascular, Dpto de Medicina, Fundación INCLIVA Hospital Clínico, Valencia, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Millet
mesh_terms: D001921:Brain / Q000503:physiopathology*; D003128:Coma / Q000209:etiology* / Q000401:mortality / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007036:Hypothermia, Induced / Q000379:methods*; D008297:Male; D008875:Middle Aged; D058687:Out-of-Hospital Cardiac Arrest / Q000150:complications / Q000628:therapy*; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment / Q000379:methods*; D015996:Survival Rate / Q000639:trends; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000150:complications / Q000401:mortality / Q000628:therapy*
keywords: Cardiac arrest; Cerebral injury; Dominant frequency; Early prognosis; Ventricular fibrillation
references.citation: Circulation. 2012 Dec 11;126(24):2826-33
references.pmid: 23136160
references.citation: Heart Rhythm. 2014 Feb;11(2):230-6
references.pmid: 24177369
references.citation: JAMA. 2005 Jan 19;293(3):299-304
references.pmid: 15657322
references.citation: JAMA. 2006 Jan 4;295(1):50-7
references.pmid: 16391216
references.citation: Am Heart J. 1989 Jan;117(1):151-9
references.pmid: 2911968
references.citation: Crit Care Med. 2012 Apr;40(4):1192-8
references.pmid: 22202708
references.citation: Resuscitation. 1991 Aug;22(1):85-91
references.pmid: 1658897
references.citation: JAMA. 1995 Dec 27;274(24):1922-5
references.pmid: 8568985
references.citation: JAMA. 2009 Nov 25;302(20):2222-9
references.pmid: 19934423
references.citation: Heart Rhythm. 2011 May;8(5):740-9
references.pmid: 21185950
references.citation: Ann Emerg Med. 1989 Nov;18(11):1181-5
references.pmid: 2817561
references.citation: Antioxid Redox Signal. 2003 Oct;5(5):597-607
references.pmid: 14580316
references.citation: Am J Emerg Med. 1986 Jan;4(1):72-86
references.pmid: 2868736
references.citation: Am J Cardiol. 2003 Aug 15;92(4):457-9
references.pmid: 12914879
references.citation: Resuscitation. 1996 Dec;33(2):155-61
references.pmid: 9025132
references.citation: Q J Med. 1992 Oct;85(306):761-9
references.pmid: 1287707
references.citation: N Engl J Med. 2013 Dec 5;369(23):2197-206
references.pmid: 24237006
references.citation: Intensive Care Med. 2007 Feb;33(2):237-45
references.pmid: 17019558
references.citation: Resuscitation. 2005 Apr;65(1):49-55
references.pmid: 15797275
references.citation: N Engl J Med. 2002 Feb 21;346(8):557-63
references.pmid: 11856794
references.citation: Crit Care Med. 1995 Jan;23(1):18-25
references.pmid: 8001370
references.citation: N Engl J Med. 2002 Feb 21;346(8):549-56
references.pmid: 11856793
references.citation: Lancet. 1975 Mar 1;1(7905):480-4
references.pmid: 46957
references.citation: Geriatrics. 1991 Jul;46(7):54-8, 63, 66
references.pmid: 2060803
references.citation: Circulation. 2012 Jun 19;125(24):3004-12
references.pmid: 22623717
references.citation: Anesth Analg. 1994 Sep;79(3):434-8
references.pmid: 8067545
references.citation: Neth Heart J. 2015 Jan;23(1):20-5
references.pmid: 25326102
references.citation: Circulation. 2013 Aug 27;128(9):995-1002
references.pmid: 23979627
references.citation: Resuscitation. 2001 Nov;51(2):151-8
references.pmid: 11718970
references.citation: JAMA. 2002 Dec 18;288(23):3008-13
references.pmid: 12479765