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Use of the low-frequency/high-frequency ratio of heart rate variability to predict short-term deterioration in emergency department patients with sepsis
  1. Douglas P Barnaby1,
  2. Shannon M Fernando2,
  3. Kevin J Ferrick3,
  4. Christophe L Herry4,
  5. Andrew J E Seely4,5,
  6. Polly E Bijur1,
  7. E John Gallagher1
  1. 1 Department of Emergency Medicine, Albert Einstein College of Medicine, Bronx, New York, USA
  2. 2 Department of Emergency Medicine, University of Ottawa, Ottawa, Ontario, Canada
  3. 3 Department of Medicine, Division of Cardiology, Albert Einstein College of Medicine, Bronx, New York, USA
  4. 4 Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
  5. 5 Departments of Surgery and Critical Care Medicine, University of Ottawa Faculty of Medicine, Ottawa, Ontario, Canada
  1. Correspondence to Dr Douglas P Barnaby, Department of Emergency Medicine, Montefiore Medical Center, 3411 Wayne Ave, #651, Bronx, NY 10467, USA; dbarnaby{at}


Objective To examine the ability of the low-frequency/high-frequency (LF/HF) ratio of heart rate variability (HRV) analysis to identify patients with sepsis at risk of early deterioration.

Methods This is a prospective observational cohort study of patients with sepsis presenting to the Montefiore Medical Center ED from December 2014 through September 2015. On presentation, a single ECG Holter recording was obtained and analysed to obtain the LF/HF ratio of HRV. Initial Sequential Organ Failure Assessment (SOFA) scores were computed. Patients were followed for 72 hours to identify those with early deterioration.

Results 466 patients presenting to the ED with sepsis were analysed. Thirty-two (7%) reached at least one endpoint within 72 hours. An LF/HF ratio <1 had a sensitivity and specificity of 34% (95% CI (19% to 53%)) and 82% (95% CI (78% to 85%)), respectively, with positive and negative likelihood ratios of 1.9 (95% CI (1.1 to 3.2)) and 0.8 (95% CI (0.6 to 1.0)). An initial SOFA score ≥3 had a sensitivity and specificity of 38% (95% CI (22% to 56%)) and 92% (95% CI (89% to 95%)), with positive and negative likelihood ratios of 4.9 (95% CI (2.8 to 8.6)) and 0.7 (95% CI (0.5 to 0.9)). The composite measure of HRV+SOFA had improved sensitivity (56%, 95% CI (38% to 73%)) but at the expense of specificity (77%, 95% CI (72% to 80%)), with positive and negative likelihood ratios of 2.4 (95% CI (1.7 to 3.4)) and 0.6 (95% CI (0.4 to 0.9)). Receiver operating characteristic analysis did not identify a superior alternate threshold for the LF/HF ratio. Kaplan-Meier survival functions differed significantly (p=0.02) between low (<1) and high (≥1) LF/HF groups.

Conclusions While we found a statistically significant relationship between HRV, SOFA and HRV+SOFA, and early deterioration, none reliably functioned as a clinical predictive tool. More complex multivariable models will likely be required to construct models with clinical utility.

  • ECG
  • methods
  • infectious diseases
  • intensive care
  • resuscitation
  • clinical care

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  • Contributors DPB, PEB and EJG conceived and designed the study. DPB and PEB supervised data collection and managed its retrieval and storage. DPB, PEB, CLH, AJES and EJG provided statistical advice on study design and analysed the data. DPB and PEB drafted the manuscript. All authors contributed substantially to its revision. DPB takes responsibility for the paper as a whole.

  • Funding The research described was supported by NIH/National Center for Advancing Translational Sciences (NCATS) Einstein-Montefiore CTSA Grant Number UL1TR001073. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the NCRR or NIH.

  • Competing interests AJES founded Therapeutic Monitoring Systems in order to commercialise patented Continuous Individualized Multiorgan Variability Analysis (CIMVA) technology, with the objective of delivering variability-directed clinical decision support to improve quality and efficiency of care. CLH is a patent holder related to waveform quality assessment necessary for variability analysis. The remaining authors report no potential conflicts of interest.

  • Patient consent Obtained.

  • Ethics approval Albert Einstein College of Medicine Institutional Review Board, Bronx, New York, USA.

  • Provenance and peer review Not commissioned; externally peer reviewed.