Prognostic Value of Ventricular Fibrillation Spectral Analysis in Sudden Cardiac Death

NCT03248557 | Completed

• 1 other identifier: 16/405-E
• Study Type: observational
• Target: 168
• Locations: 1 country
• Sites: 5

Brief Summary

Ventricular fibrillation (VF)-related sudden cardiac death (SCD) is a leading cause of mortality. Patients may survive with neurological damage despite state-of-the-art treatment. Current biological and imaging parameters show significant limitations on early predicting cerebral performance at hospital admission. A spectral-based model was recently suggested to correlate time-dependent VF spectral changes with acute cerebral injury in comatose survivors after cardiac arrest, which opens the possibility to implement early prognostic tools in clinical practice. The AWAKE trial is an investigator-initiated, multicenter, observational trial aiming to validate a spectral-based model to early predict cerebral performance and survival in resuscitated comatose survivors admitted to specialized intensive care units. The primary clinical outcome is favorable neurological performance (FNP) during hospitalization. Patients will be categorized into 4 subsets of NP according to the risk score obtained from the predictive model. The secondary clinical outcomes are survival to hospital discharge, and FNP and survival after 6 months of follow-up. Model-derived categorization will be compared with clinical outcomes to assess model sensitivity, specificity and accuracy. Eligible patients will be included prospectively and retrospectively, using an electronic Case Report Form to enter data from medical records and in-person interviews. Patients will be divided into: study group (predictive data required) including comatose (Glasgow Coma Scale -GCS- ≤8) survivors undergoing temperature control after return of spontaneous circulation (RoSC), and control group including patients who regain consciousness (GCS=15) after RoSC. VF tracings prior to the first DC shock will be digitized and analyzed to derive spectral data and risk scores.

Conditions

Sudden Cardiac Death; Ventricular Fibrillation; Reperfusion Injury

Keywords

resuscitation; wavelet analysis; spectral analysis; post-cardiac arrest syndrome

Outcome Measures

Primary Outcomes (1)

• Favorable neurological performance (FNP) during hospitalization

  Patients will be assessed using the Pittsburgh Cerebral Performance Categories (CPC) outcome categorization of brain injury. They will be considered to have FNP if they score 1 or 2 in the CPC scale (good performance and moderate disability, respectively). CPCs 3, 4 and 5 (severe disability, vegetative state and brain death, respectively) will be considered as a non-FNP. In the prospective cohort, FNP will also be determined using the mini-mental state examination (cut-off value 24/30).

  Hospitalization, up to 2 months after admission

Secondary Outcomes (3)

• Survival to hospital discharge

  Hospitalization, up to 2 months

• Favorable neurological performance (FNP) at follow-up

  6 months after discharge (prospective patients) or at patient enrollment (retrospective patients)

• Survival at follow-up

  6 months after discharge (prospective patients) or at patient enrollment (retrospective patients)

Study Arms (2)

Study

Comatose survivors (GCS ≤8) after RoSC, in whom neurological prognosis is unknown at the time of admission. Neurological performance of patients from the study group (prospective and retrospective) will be categorized according to a risk score obtained from the multivariate spectral-based model.

Diagnostic Test: Spectral analysis of ventricular fibrillation tracings

Control

Patients who are conscious (GCS=15) and whose neurological status is known and good at admission.

Diagnostic Test: Spectral analysis of ventricular fibrillation tracings

Interventions

Spectral analysis of ventricular fibrillation tracings DIAGNOSTIC_TEST

Up to 5-s long ventricular fibrillation segments will be extracted after segmentation and signal codification from artifact-free tracings. Signals will be band-pass filtered between 1.5 and 40 Hz. Averaged power spectral density will be obtained at each frequency using the non-parametric Welch method for using fast Fourier transform and normalized to the peak power in the 1.5-10 Hz band for each patient. Dominant frequency, HL-PSDR (the relative power between high and low frequency bands (cut-off: 3.9 Hz)) and HL-pKR ( relative number of spectral peaks above and below the 3.9 Hz threshold with power above 40% the frequency with the highest power), along with the number of DC shocks before ROSC, will be the variables used to obtain a model-derived risk score for outcome prediction.

Control; Study

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Consecutive patients admitted to the hospital after out or in-hospital cardiac arrest due to VF will be registered and screened for potential inclusion in the study. Patients will be classified into either of two groups: 1. Study group: comatose survivors (GCS ≤8) after RoSC, in whom neurological prognosis is unknown at the time of admission. This group is divided into a prospective cohort (new admissions), and a retrospective one, in which cases will be obtained from existing databases in the participating centers. 2. Control group: patients who are conscious (GCS=15) and whose neurological status is known and good at admission. This will be the control group for the spectral-based predictive model (gold standard for FNP).

You may qualify if:

• In or out-of-hospital cardiac arrest with ventricular fibrillation (VF) as first documented rhythm.
• A ≥3-second VF tracings before the first direct current (DC) shock.
• Signed informed consent. Patients unable to consent, it will be requested to an authorized relative.
• Study group: GCS ≤8 and subject to temperature management (hypothermia 32-34ºC or normothermia 36ºC).
• Control group: GCS=15, thus no indication for temperature management.

You may not qualify if:

• First documented rhythm other than VF (e.g. ventricular tachycardia, pulseless electrical activity, asystole)
• Unavailable or suboptimal quality of the ECG tracing before the first DC shock.
• Terminal disease or cognitive impairment before the SCD event.
• Other possible causes of comatose status different from SCD (e.g. drugs, traumatic brain injury, hypoxia).
• Aged under 18 .
• Unwilling to provide the informed consent.
• Comatose status (GCS≤8) and absence of temperature management or GCS ≥9 if temperature management was undertaken.
• Hemodynamic instability leading to incomplete 24 h of temperature management
• Early mortality and absence of subsequent withdrawal of sedation to assess cerebral performance.

Sponsors & Collaborators

• Hospital San Carlos, Madrid: lead
• Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III: collaborator
• Hospital Universitario La Paz: collaborator
• Hospital General de Ciudad Real: collaborator
• Fundación de Investigación en Red en Enfermedades Cardiovasculares: collaborator
• Hospital General Universitario Gregorio Marañon: collaborator
• Spanish Society of Cardiology: collaborator
• Fundacion Investigacion Interhospitalaria Cardiovascular: collaborator

Study Sites (5)

Hospital General Universitario de Ciudad Real

Ciudad Real, 13005, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, 28007, Spain

Location

Fundación Centro Nacional de Investigaciones Cardiovasculares, Carlos III

Madrid, 28029, Spain

Location

Hospital Clínico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Related Publications (3)

• Priori SG, Blomstrom-Lundqvist C, Mazzanti A, Blom N, Borggrefe M, Camm J, Elliott PM, Fitzsimons D, Hatala R, Hindricks G, Kirchhof P, Kjeldsen K, Kuck KH, Hernandez-Madrid A, Nikolaou N, Norekval TM, Spaulding C, Van Veldhuisen DJ; ESC Scientific Document Group. 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC). Eur Heart J. 2015 Nov 1;36(41):2793-2867. doi: 10.1093/eurheartj/ehv316. Epub 2015 Aug 29. No abstract available.

  PMID: 26320108 BACKGROUND

• Filgueiras-Rama D, Calvo CJ, Salvador-Montanes O, Cadenas R, Ruiz-Cantador J, Armada E, Rey JR, Merino JL, Peinado R, Perez-Castellano N, Perez-Villacastin J, Quintanilla JG, Jimenez S, Castells F, Chorro FJ, Lopez-Sendon JL, Berenfeld O, Jalife J, Lopez de Sa E, Millet J. Spectral analysis-based risk score enables early prediction of mortality and cerebral performance in patients undergoing therapeutic hypothermia for ventricular fibrillation and comatose status. Int J Cardiol. 2015;186:250-8. doi: 10.1016/j.ijcard.2015.03.074. Epub 2015 Mar 14.

  PMID: 25828128 RESULT

• Palacios-Rubio J, Marina-Breysse M, Quintanilla JG, Gil-Perdomo JM, Juarez-Fernandez M, Garcia-Gonzalez I, Rial-Baston V, Corcobado MC, Espinosa MC, Ruiz F, Gomez-Mascaraque Perez F, Bringas-Bollada M, Lillo-Castellano JM, Perez-Castellano N, Martinez-Selles M, Lopez de Sa E, Martin-Benitez JC, Perez-Villacastin J, Filgueiras-Rama D. Early prognostic value of an Algorithm based on spectral Variables of Ventricular fibrillAtion from the EKG of patients with suddEn cardiac death: A multicentre observational study (AWAKE). Arch Cardiol Mex. 2018 Dec;88(5):460-467. doi: 10.1016/j.acmx.2018.05.003. Epub 2018 Jun 7.

  PMID: 29885765 DERIVED

MeSH Terms

Conditions

Death, Sudden, Cardiac; Ventricular Fibrillation; Reperfusion Injury; Post-Cardiac Arrest Syndrome

Condition Hierarchy (Ancestors)

Heart Arrest; Heart Diseases; Cardiovascular Diseases; Death, Sudden; Death; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Arrhythmias, Cardiac; Vascular Diseases; Postoperative Complications; Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• David Filgueiras-Rama, MD

  Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III

  PRINCIPAL INVESTIGATOR

• Manuel Marina-Breysse, MD

  Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III

  STUDY CHAIR

• María-Jesús García-Torrent, PharmD, PhD

  Hospital San Carlos, Madrid

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: August 7, 2017
• First Posted: August 14, 2017
• Study Start: June 1, 2016
• Primary Completion: September 1, 2022
• Study Completion: March 1, 2023
• Last Updated: March 7, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

ES (5)