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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