1. Evaluation Of A Novel Non Model Driven Assessment Of Cardiac Autonomic Activity: Reinnervation After Human Heart Transplantation R. Schondorf, J. Benoit, M. Genoulaz, M.J. Lafitte and L. Bernardi

2. Where Is The Fish? You are watching one particular fish inside a school of fish You are watching one particular fish inside a school of fish Where the fish is now depends on where it has been Where the fish is now depends on where it has been Where the fish is going depends on where it is now Where the fish is going depends on where it is now

3. Where Is The Fish? This fish can be anywhere within the school of fish This fish can be anywhere within the school of fish A small school of fish looks just like a small part of a big school of fish A small school of fish looks just like a small part of a big school of fish

4. Analysis of R-R Intervals Is Not A Fishing Expedition By their very nature R-R intervals are discrete events By their very nature R-R intervals are discrete events They display the property of self similarity (behave like fish) They display the property of self similarity (behave like fish) The behavior of R-R intervals is a lot simpler than the Dow Jones The behavior of R-R intervals is a lot simpler than the Dow Jones

5. What Was Found Without Knowing What An R-R Interval Is? Two separate functions describe the kinematics of the system Two separate functions describe the kinematics of the system Because we do not know where we are, each function is expressed as a velocity Because we do not know where we are, each function is expressed as a velocity Each function can be reduced to a scalar that describes what is most probable Each function can be reduced to a scalar that describes what is most probable

6. Aim Of The Present Study To characterize the physiological underpinnings of the present tools using a robust well-characterized data set To characterize the physiological underpinnings of the present tools using a robust well-characterized data set

8. Advantage Of This Data Set Patients with heart transplant are initially cardiodenervated Patients with heart transplant are initially cardiodenervated There are multiple lines of evidence suggesting modest cardiac sympathetic reinnervation over time There are multiple lines of evidence suggesting modest cardiac sympathetic reinnervation over time There is no evidence that cardiovagal reinnervation occurs There is no evidence that cardiovagal reinnervation occurs

9. Advantage Of This Data Set Both controls and patients were subject to rhythmic neck suction at 0.1 Hz Both controls and patients were subject to rhythmic neck suction at 0.1 Hz We know what neck suction does We know what neck suction does

10. What Do We Know Already Atropine reduces one of the parameters (the green one) to 0 Atropine reduces one of the parameters (the green one) to 0 Atenolol variably reduces the fluctuations of the other parameter (the blue one) Atenolol variably reduces the fluctuations of the other parameter (the blue one) Head-up tilt increases the magnitude and fluctuation of this other parameter Head-up tilt increases the magnitude and fluctuation of this other parameter

11. Control (1)

14. Control (2)

17. Control (3)

20. Control (4)

22. Transplant (1)

24. Transplant (2)

26. Transplant (3)

28. Transplant (4)

30. Conclusions The response of our 2 parameters to rhythmic neck suction in control subjects approximates well worked out physiology The response of our 2 parameters to rhythmic neck suction in control subjects approximates well worked out physiology Our method independently confirms preferential sympathetic reinnervation and essentially absent parasympathetic reinnervation in the transplanted heart Our method independently confirms preferential sympathetic reinnervation and essentially absent parasympathetic reinnervation in the transplanted heart

31. Problems To Be Addressed What is the meaning of the 2 beat phase shift of the vagal parameter? What is the meaning of the 2 beat phase shift of the vagal parameter? What is the cause of the baseline shift in the sympathetic parameter in the absence of parasympathetic cardiac innervation? What is the cause of the baseline shift in the sympathetic parameter in the absence of parasympathetic cardiac innervation?