Supportive Care in Cancer

, Volume 26, Issue 9, pp 3289–3296 | Cite as

Heart rate variability for rapid risk stratification of emergency patients with malignant disease

  • K. Boehm
  • M. Duckheim
  • L. Mizera
  • P. Groga-Bada
  • N. Malek
  • F. Kreth
  • M. Gawaz
  • C. S. Zuern
  • C. Eick
Original Article



Neoplasms are the second most common diseases in western countries. Many patients with malignant diseases repeatedly present themselves in the emergency department (ED). Due to limited capacities, appropriate risk stratification strategies for cancer patients have to be developed. This study assesses if deceleration capacity (DC) of heart rate as a parameter of heart rate variability predicts mortality in emergency patients with malignant diseases.


Prospectively, 140 adults with different entities of malignant diseases who presented in the medical ED were included. Primary and secondary endpoints were intrahospital mortality and mortality within 180 days, respectively. We calculated DC from short-term ECG readings of the surveillance monitors. Additionally, the Modified Early Warning Score (MEWS) and laboratory parameters such as white blood cells (WBC), lactate dehydrogenase, serum hemoglobin, and serum creatinine were determined.


The median age of the patients was 65 ± 14 years. 19.3% of the patients died within the hospital stay and 57.9% died within 180 days. DC and WBC were independent predictors of intrahospital death reaching a hazard ratio (HR) of 0.79 (95% confidence interval (CI) 0.63–0.993, p = 0.043) and of 1.00 (95% CI 1.00–1.00, p = 0.003), respectively. DC and serum creatinine independently predicted death within 180 days (HR 0.90, 95% CI 0.82–0.98, p = 0.023 and HR 1.41, 95% CI 1.05–1.90, p = 0.018, respectively).


Deceleration capacity of heart rate is suitable for rapid risk assessment of emergency patients with malignant diseases.


Heart rate variability Deceleration capacity Risk prediction Cancer Malignant diseases Emergency department 


Compliance with ethical standards

The study got approval from the Clinical Ethics Committee of the University Hospital Tuebingen. The need for written informed consent was waived by the ethics committee.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Van Galen LS, Dijkstra CC, Ludikhuize J, Kramer MH, Nanayakkara PW (2016) A protocolised once a day Modified Early Warning Score (MEWS) measurement is an appropriate screening tool for major adverse events in a general hospital population. PLoS One 11(8):e0160811CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Löllgen H (1999) Herzfrequenzvariabilität. Dt Ärztebl 96:A-2029–A-2032 [Heft 31–32]Google Scholar
  3. 3.
    Harris PR, Stein PK, Fung GL, Drew BJ (2014) Heart rate variability measured early in patients with evolving acute coronary syndrome and 1-year outcomes of rehospitalization and mortality. Vasc Health Risk Manag 10:451–464CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Ong ME, Goh K, Fook-Chong S, Haaland B, Wai KL, Koh ZX et al (2013) Heart rate variability risk score for prediction of acute cardiac complications in ED patients with chest pain. Am J Emerg Med 31(8):1201–1207CrossRefPubMedGoogle Scholar
  5. 5.
    Bauer A, Kantelhardt JW, Barthel P, Schneider R, Mäkikallio T, Ulm K, Hnatkova K, Schömig A, Huikuri H, Bunde A, Malik M, Schmidt G (2006) Deceleration capacity of heart rate as a predictor of mortality after myocardial infarction: cohort study. Lancet 367:1674–1681CrossRefPubMedGoogle Scholar
  6. 6.
    Zuern CS, Rizas KD, Eick C, Vogtt MI, Bigalke B, Gawaz M, Bauer A (2014) Severe autonomic failure as a predictor of mortality in aortic valve stenosis. Int J Cardiol 176(3):782–787CrossRefPubMedGoogle Scholar
  7. 7.
    Poreba M, Poreba R, Gac P, Usnarska-Zubkiewicz L, Pilecki W, Piotrowicz E et al (2014) Heart rate variability and heart rate turbulence in patients with hematologic malignancies subjected to high-dose chemotherapy in the course of hematopoietic stem cell transplantation. Ann Noninvasive Electrocardiol 19(2):157–165CrossRefPubMedGoogle Scholar
  8. 8.
    Ahmad S, Ramsay T, Huebsch L, Flanagan S, McDiarmid S, Batkin I, McIntyre L, Sundaresan SR, Maziak DE, Shamji FM, Hebert P, Fergusson D, Tinmouth A, Seely AJE (2009) Continuous multi-parameter heart rate variability analysis heralds onset of sepsis in adults. PLoS One 4(8):e6642CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Chen WL, Chen JH, Huang CC, Kuo CD, Huang CI, Lee LS (2008) Heart rate variability measures as predictors of in-hospital mortality in ED patients with sepsis. Am J Emerg Med 26(4):395–401CrossRefPubMedGoogle Scholar
  10. 10.
    Guo Y, Koshy S, Hui D, Palmer JL, Shin K, Bozkurt M, Wamique Yusuf S (2015) Prognostic value of heart rate variability in patients with cancer. J Clin Neurophysiol 32(6):516–520CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Zhou X, Ma Z, Zhang L, Zhou S, Wang J, Wang B, Fu W (2016) Heart rate variability in the prediction of survival in patients with cancer: a systematic review and meta-analysis. J Psychosom Res 89:20–25CrossRefPubMedGoogle Scholar
  12. 12.
    De Couck M, Gidron Y (2013) Norms of vagal nerve activity, indexed by heart rate variability, in cancer patients. Cancer Epidemiol 37(5):737–741CrossRefPubMedGoogle Scholar
  13. 13.
    Arab C, Dias DP, Barbosa RT, Carvalho TD, Valenti VE, Crocetta TB et al (2016) Heart rate variability measure in breast cancer patients and survivors: a systematic review. Psychoneuroendocrinology 68:57–68CrossRefPubMedGoogle Scholar
  14. 14.
    Guo Y, Palmer JL, Strasser F, Yusuf SW, Bruera E (2013) Heart rate variability as a measure of autonomic dysfunction in men with advanced cancer. Eur J Cancer Care (Engl) 22(5):612–616CrossRefGoogle Scholar
  15. 15.
    Chiang JK, Kuo TB, Fu CH, Koo M (2013) Predicting 7-day survival using heart rate variability in hospice patients with non-lung cancers. PLoS One 8(7):e69482CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Wang YM, Wu HT, Huang EY, Kou YR, Hseu SS (2013) Heart rate variability is associated with survival in patients with brain metastasis: a preliminary report. Biomed Res Int 2013:503421PubMedPubMedCentralGoogle Scholar
  17. 17.
    Statistisches Bundesamt. Todesursachen nach Krankheitsarten 2014. Wiesbaden 2015Google Scholar
  18. 18.
    Ferrat E, Paillaud E, Laurent M, Le Thuaut A, Caillet P, Tournigand C et al (2015) Predictors of 1-year mortality in a prospective cohort of elderly patients with cancer. J Gerontol A Biol Sci Med Sci 70(9):1148–1155CrossRefPubMedGoogle Scholar
  19. 19.
    Lian J, Wang L, Muessig D (2011) A simple method to detect atrial fibrillation using RR intervals. Am J Cardiol 107(10):1494–1497CrossRefPubMedGoogle Scholar
  20. 20.
    Eick C, Rizas KD, Meyer-Zurn CS, Groga-Bada P, Hamm W, Kreth F et al (2015) Autonomic nervous system activity as risk predictor in the medical emergency department: a prospective cohort study. Crit Care Med 43(5):1079–1086CrossRefPubMedGoogle Scholar
  21. 21.
    Eick C, Rizas KD, Zuern CS, Bauer A (2014) Automated assessment of cardiac autonomic function by means of deceleration capacity from noisy, nonstationary ECG signals: validation study. Ann Noninvasive Electrocardiol: Off J Int Soc Holter Noninvasive Electrocardiol Inc 19:122–128CrossRefGoogle Scholar
  22. 22.
    Bauer A, Kantelhardt JW, Bunde A, Barthel P, Schneider R, Malik M, Schmidt G (2006) Phase-rectified signal averaging detects quasi-periodicities in non-stationary data. Phys A Stat Mech Appl 364:423–434CrossRefGoogle Scholar
  23. 23.
    Bauer A, Kantelhardt JW, Barthel P, Schneider R, Makikallio T, Ulm K et al (2006) Deceleration capacity of heart rate as a predictor of mortality after myocardial infarction: cohort study. Lancet 367(9523):1674–1681CrossRefPubMedGoogle Scholar
  24. 24.
    Subbe CP, Kruger M, Rutherford P, Gemmel L (2001) Validation of a modified Early Warning Score in medical admissions. QJM 94(10):521–526CrossRefPubMedGoogle Scholar
  25. 25.
    Duckheim M, Klee K, Gotz N, Helle P, Groga-Bada P, Mizera L et al (2017) Deceleration capacity as a risk predictor in patients presenting to the emergency department with syncope: a prospective exploratory pilot study. Medicine (Baltimore) 96(49):e8605CrossRefGoogle Scholar
  26. 26.
    Duckheim M, Bensch C, Kittlitz L, Gotz N, Klee K, Groga-Bada P et al (2017) Deceleration capacity of heart rate predicts 1-year mortality of patients undergoing transcatheter aortic valve implantation. Clin Cardiol 40(10):919–924CrossRefPubMedGoogle Scholar
  27. 27.
    Zentrum für Krebsregisterdaten. Robert Koch Institut. Verbreitung von Krebserkrankungen in Deutschland. Krebs Gesamt- Ergebnisse zur Prävalenz. S. 157Google Scholar
  28. 28.
    Kostakou E, Rovina N, Kyriakopoulou M, Koulouris NG, Koutsoukou A (2014) Critically ill cancer patient in intensive care unit: issues that arise. J Crit Care 29(5):817–822CrossRefPubMedGoogle Scholar
  29. 29.
    De Couck M, van Brummelen D, Schallier D, De Greve J, Gidron Y (2013) The relationship between vagal nerve activity and clinical outcomes in prostate and non-small cell lung cancer patients. Oncol Rep 30(5):2435–2441CrossRefPubMedGoogle Scholar
  30. 30.
    Gidron Y, De Couck M, De Greve J (2014) If you have an active vagus nerve, cancer stage may no longer be important. J Biol Regul Homeost Agents 28(2):195–201PubMedGoogle Scholar
  31. 31.
    Adams SC, Schondorf R, Benoit J, Kilgour RD (2015) Impact of cancer and chemotherapy on autonomic nervous system function and cardiovascular reactivity in young adults with cancer: a case-controlled feasibility study. BMC Cancer 15:414CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Walsh D, Nelson KA (2002) Autonomic nervous system dysfunction in advanced cancer. Support Care Cancer 10(7):523–528CrossRefPubMedGoogle Scholar
  33. 33.
    Niederer D, Vogt L, Thiel C, Schmidt K, Bernhorster M, Lungwitz A et al (2013) Exercise effects on HRV in cancer patients. Int J Sports Med 34(1):68–73PubMedGoogle Scholar
  34. 34.
    Shankar A, Wang JJ, Rochtchina E, Yu MC, Kefford R, Mitchell P (2006) Association between circulating white blood cell count and cancer mortality: a population-based cohort study. Arch Intern Med 166(2):188–194CrossRefPubMedGoogle Scholar
  35. 35.
    Na SY, Sung JY, Chang JH, Kim S, Lee HH, Park YH, Chung W, Oh KH, Jung JY (2011) Chronic kidney disease in cancer patients: an independent predictor of cancer-specific mortality. Am J Nephrol 33(2):121–130CrossRefPubMedGoogle Scholar
  36. 36.
    Wulaningsih W, Holmberg L, Garmo H, Malmstrom H, Lambe M, Hammar N, Walldius G, Jungner I, Ng T, van Hemelrijck M (2015) Serum lactate dehydrogenase and survival following cancer diagnosis. Br J Cancer 113(9):1389–1396CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Lardaro T, Self WH, Barrett TW (2015) Thirty-day mortality in ED patients with new onset atrial fibrillation and actively treated cancer. Am J Emerg Med 33(10):1483–1488CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • K. Boehm
    • 1
  • M. Duckheim
    • 1
  • L. Mizera
    • 1
  • P. Groga-Bada
    • 1
  • N. Malek
    • 2
  • F. Kreth
    • 2
  • M. Gawaz
    • 1
  • C. S. Zuern
    • 1
    • 3
  • C. Eick
    • 1
  1. 1.Department of CardiologyUniversity Hospital TubingenTubingenGermany
  2. 2.Department of Internal Medicine IUniversity Hospital TubingenTubingenGermany
  3. 3.Department of CardiologyUniversity Hospital BaselBaselSwitzerland

Personalised recommendations