Evaluation Of A Novel Non Model Driven Evaluation Of A Novel Non Model Driven Assessment Of Cardiac Autonomic Assessment Of Cardiac Autonomic Activity: Reinnervation After Human Activity: Reinnervation After Human

Heart TransplantationHeart Transplantation

R. Schondorf, J. Benoit, M. Genoulaz, R. Schondorf, J. Benoit, M. Genoulaz, M.J. Lafitte and L. BernardiM.J. Lafitte and L. Bernardi

Where Is The Fish?Where Is The Fish?

• You are watching You are watching one particular fish one particular fish inside a school of inside a school of fishfish• Where the fish is Where the fish is

now depends on now depends on where it has beenwhere it has been• Where the fish is Where the fish is

going depends on going depends on where it is nowwhere it is now

Where Is The Fish?Where Is The Fish?

• This fish can be This fish can be anywhere within anywhere within the school of fishthe school of fish• A small school of A small school of

fish looks just like fish looks just like a small part of a big a small part of a big school of fishschool of fish

Analysis of R-R Intervals Is Not A Fishing Analysis of R-R Intervals Is Not A Fishing ExpeditionExpedition

• By their very nature R-R intervals are By their very nature R-R intervals are discrete eventsdiscrete events• They display the property of self They display the property of self

similarity (behave like fish)similarity (behave like fish)• The behavior of R-R intervals is a lot The behavior of R-R intervals is a lot

simpler than the Dow Jones simpler than the Dow Jones

What Was Found Without Knowing What What Was Found Without Knowing What An R-R Interval Is?An R-R Interval Is?

• Two separate functions describe the Two separate functions describe the kinematics of the system kinematics of the system • Because we do not know where we Because we do not know where we

are, each function is expressed as a are, each function is expressed as a velocityvelocity• Each function can be reduced to a Each function can be reduced to a

scalar that describes what is most scalar that describes what is most probable probable

Aim Of The Present StudyAim Of The Present Study

• To characterize the physiological To characterize the physiological underpinnings of the present tools underpinnings of the present tools using a robust well-characterized using a robust well-characterized data setdata set

Advantage Of This Data SetAdvantage Of This Data Set

• Patients with heart transplant are Patients with heart transplant are initially cardiodenervatedinitially cardiodenervated• There are multiple lines of evidence There are multiple lines of evidence

suggesting modest cardiac suggesting modest cardiac sympathetic reinnervation over timesympathetic reinnervation over time• There is no evidence that cardiovagal There is no evidence that cardiovagal

reinnervation occursreinnervation occurs

Advantage Of This Data SetAdvantage Of This Data Set

• Both controls and patients were Both controls and patients were subject to rhythmic neck suction at subject to rhythmic neck suction at 0.1 Hz0.1 Hz• We know what neck suction doesWe know what neck suction does

What Do We Know AlreadyWhat Do We Know Already

• Atropine reduces one of the Atropine reduces one of the parameters (the green one) to 0parameters (the green one) to 0• Atenolol variably reduces the Atenolol variably reduces the

fluctuations of the other parameter fluctuations of the other parameter (the blue one)(the blue one)• Head-up tilt increases the magnitude Head-up tilt increases the magnitude

and fluctuation of this other and fluctuation of this other parameterparameter

Control (1)Control (1)

Control (1)Control (1)

Control (1)Control (1)

Control (2)Control (2)

Control (2)Control (2)

Control (2)Control (2)

Control (3)Control (3)

Control (3)Control (3)

Control (3)Control (3)

Control (4)Control (4)

Control (4)Control (4)

Transplant (1)Transplant (1)

Transplant (1)Transplant (1)

Transplant (2)Transplant (2)

Transplant (2)Transplant (2)

Transplant (3)Transplant (3)

Transplant (3)Transplant (3)

Transplant (4)Transplant (4)

Transplant (4)Transplant (4)

ConclusionsConclusions

• The response of our 2 parameters to The response of our 2 parameters to rhythmic neck suction in control rhythmic neck suction in control subjects approximates well worked subjects approximates well worked out physiologyout physiology• Our method independently confirms Our method independently confirms

preferential sympathetic preferential sympathetic reinnervation and essentially absent reinnervation and essentially absent parasympathetic reinnervation in the parasympathetic reinnervation in the transplanted hearttransplanted heart

Problems To Be AddressedProblems To Be Addressed

• What is the meaning of the 2 beat What is the meaning of the 2 beat phase shift of the vagal parameter?phase shift of the vagal parameter?• What is the cause of the baseline What is the cause of the baseline

shift in the sympathetic parameter in shift in the sympathetic parameter in the absence of parasympathetic the absence of parasympathetic cardiac innervation? cardiac innervation?