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Insights from complexity science for the practice of medicine

Insights from complexity science for the practice of medicine. Robert A. Lindberg, MD Darien, CT Plexus Institute. Complexity Science. Other labels used: Chaos Theory Nonlinear Dynamics Science of Complex Adaptive Systems Systems Theory Deals with the behavior and properties of systems.

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Insights from complexity science for the practice of medicine

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  1. Insights from complexity science for the practice of medicine Robert A. Lindberg, MD Darien, CT Plexus Institute P l e x u s

  2. Complexity Science • Other labels used: • Chaos Theory • Nonlinear Dynamics • Science of Complex Adaptive Systems • Systems Theory • Deals with the behavior and properties of systems P l e x u s

  3. System definition • A collection of agents interconnected around a common purpose P l e x u s

  4. System examples • Weather system • Phone system • Internet • Stock Market • Central Nervous System • Immune System • Human Body P l e x u s

  5. Complex Dynamic System Properties Weather • Agents obey Simple Rules • Wind, water, thermodynamics, etc • Continual Dynamic Interplay between all the interconnected agents • Net consequence cannot be forecast nor engineered P l e x u s

  6. Weather patterns U N I T T I M E P l e x u s

  7. Complex Adaptive System Stock Market • Agents follow simple rules • e.g. buy low, sell high • Dynamic interplay between agents that have the ability to learn and adapt • Consequences cannot be forecast or engineered P l e x u s

  8. Dow Jones Average U N I T T I M E P l e x u s

  9. Properties of Complex Nonlinear Systems • Simple Rules underlie complexity of system • “Nonlinear” or variable • Emergent order or stability created by the dynamic interactions between the agents of the system P l e x u s

  10. Relevance of Complexity Science to Medicine • Alternative model to the Mechanistic or Reductionist Model • Understand the whole by studying the parts • The body is similar to a machine with independent parts • Concept of the human body as a complex adaptive system • Systems embedded within systems • The sum is greater than the parts P l e x u s

  11. Human Body = Complex Adaptive System • Comprised of many systems • Central Nervous System • Immune System • Cardiovascular System • G.I. System • Etc. • Systems embedded within systems P l e x u s

  12. Human Body Interacting with Larger Systems • Nature • Ecosystems • Solar Cycles • Micro-organisms • Families, Organizations • System embedded within systems P l e x u s

  13. Complexity Determinants • Number of Interconnected Agents and • Number of Connections P l e x u s

  14. Signature of Complex System behavior over time • Waves, Rhythms, Oscillations, 1/f Noise, Chaotic Resonance, Nonlinear Dynamics, etc. P l e x u s

  15. Thermostat – Closed System T E M P P l e x u s

  16. Thermostat – Open System T E M P P l e x u s

  17. Simple vs Complex Systems P l e x u s

  18. Pattern of a Simple System: two agents, one connection P l e x u s

  19. Pattern of a complex system: many agents, many connections P l e x u s

  20. Diurnal Thermostat System P l e x u s

  21. Circadian Body Temperature P l e x u s

  22. Circadian Body Temperaturewave on a wave P l e x u s

  23. Waves vs Particles • Observing the pattern of a system’s “waves” provides insight into it’s relative health and degree of complexity • Wave patterns suggest the number of agents and the number of connections and their relative responsiveness to each other P l e x u s

  24. Some examples of waves or rhythms • Heart rate • Brainwaves • Temperature curve • Action potential of nerves, muscles • Blood pressure • Hormonal pulses • Circadian rhythm P l e x u s

  25. Heart Rate Variability (HRV) • An Independent Risk Factor for All Cause Mortality • Why? • Represents a wave or rhythm indicative of the degree of physiologic health of the human system P l e x u s

  26. Normal Heart Rate Variability Beats per minute time P l e x u s

  27. Heart Rate Variability • The Heart Rate cycles in a Wave like pattern over time • A reflection of the behavior of the Cardiovascular System interacting and connected to many other agents • Its pattern has prognostic implications • A signature of complex systems behavior P l e x u s

  28. Abnormal Heart Rate Variability Beats Per minute time P l e x u s

  29. Chronotropic Response Beats per minute with exercise time P l e x u s

  30. Usefulness of impaired chronotropic response to exercise as a predictor of mortality • Chronotropic incompetence is a strong and independent predictor of death, even after accounting for angio severity of CAD • 384 pt’s for Thallium stress tests • Dresing;Am J Cardiol 2000;86:602 P l e x u s

  31. Prognostic implications of chronotropic incompetence in the Framingham Heart Study • An attenuated heart rate response to exercise is predictive of increased mortality and coronary heart disease incidence • 1575 males, mean age 43, prospective • Lauer;Circulation.1996;93:1520 P l e x u s

  32. Effects of exercise training on chronotropic incompetence in pt’s with heart failure • Exercise results in an increase in peak heart rate and partial reversal of chronotropic incompetence in patients with stable heart failure • Keteyian; Am Heart J. 1999;138:233 P l e x u s

  33. Heart Rate Recovery Beats per minute time P l e x u s

  34. Heart-Rate Recovery Immediately After Exercise as a Predictor of Mortality • A delayed decrease in the heart rate during the first minute after graded exercise…is a powerful and independent predictor of the risk of death • Cole; NEJM 1999;341:1351-7 P l e x u s

  35. Heart Rate Recovery after Submaximal Exercise Testing as a Predictor of Mortality • Healthy Cohorts, routine testing • Heart rate recovery 2 minutes after ETT • Reduced HR recovery a powerful independent predictor of mortality in healthy adults • Cole; Annals of Int Med. 2000;132:552 P l e x u s

  36. Heart rate variability + Chronotropic response Heart rate recovery P l e x u s

  37. Heart Rate Variability Beats per minute time P l e x u s

  38. Normal Heart Rate Variability rest exertion P l e x u s

  39. Decreased Heart Rate Variability exertion rest P l e x u s

  40. Decreased HRV and its association with increased mortality after acute MI • Multicenter Post-Infarction research group • Reduced HRV post MI poor prognosis independent of traditional risk factors • Kleiger. Am J Cardiol. 1987;59:256 P l e x u s

  41. HRV as a predictor of mortality in the Elderly • Random sample of elderly over 65, # 347 followed for 10 yrs • Prognostic power of traditional risk factors compared • 24 hr HRV best predictor of death in elderly subjects • Circulation 1998;97:2031 P l e x u s

  42. Reduced Heart Rate Variability and Mortality Risk in an Elderly Cohort • 2 hour Holter Moniter analysis • Estimation of HRV offers prognostic information for all cause mortality beyond that provided by evaluation of traditional risk factors • Circulation. 1994;90:878-883 • Framingham Heart Study P l e x u s

  43. HRV Components • The Wave Model of HRV • Amplitude • Rate of Change • Degree of Change • Frequency • Variation in frequency rate P l e x u s

  44. HRV Amplitude-- degree of change good bad P l e x u s

  45. HRV Amplitude-- rate of change good bad P l e x u s

  46. HRV Frequency good bad P l e x u s

  47. Cardiac Interbeat Interval Dynamics From Childhood to Senescence • Healthy aging is associated with a loss of complex variability in R-R intervals • New methods of R-R interval variability based on nonlinear dynamics may give insight into heart rate dynamics • Pikkujamsa;Circulation.1999;100:393 P l e x u s

  48. Heritability of HRVThe Framingham Heart Study • Holter moniter data, comparing siblings • “Heritable factors may explain a substantial proportion of the variance in HR and HRV” • Singh;Circulation.1999;99:2251 P l e x u s

  49. Association of Depression With Reduced HRV in Coronary Artery Disease • Depressed patients with CAD have decreased HRV compared with nondepressed CAD patients even after adjusting for relevant covariates • Decreased HRV may explain the increased risk for cardiac mortality and morbidity in depressed patients • Carney;Am J Cardiol 1995;76:562 P l e x u s

  50. HRV in healthy middle age pts, post MI pts and heart transplants • HRV excellent predictor of death of any cause or arrhythmic death • Heart Transplant most reduced HRV • Circulation. 1996;93:2142 P l e x u s

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