hello i'm David Haines from beaumont hospital in royal oak michigan and i'm really thrilled
to be part of cast af2 it's a great lineup today and i'm proud to be part of the faculty
today i'm going to talk about the biophysics of pulse field ablation this is a really hot area
tremendous interest and i do think it will be the future of our field in afib ablation so comparing
our eth ablation to pulse field the main thing about the two technologies is the therapeutic
range we can make effective lesions with radio frequency ablation but when there are collateral
tissues that can be damaged the range of energy delivery is narrow and you can end up with
collateral damage while you're trying to achieve therapeutic effect whereas with pulse field
we get effective myocardial ablation with relative sparing of the neighboring tissues so this is
really a favorable technology now the determinants of electroporation success have to do with
dielectric breakdown of the membrane by a voltage field and you can see this cartoon of a biphasic
field and the electromotive force that it's exerting on the cell membrane with high enough
field strength you start to get breakdown of that membrane until you actually have
poor formation and this uh simulation shows the effect of the lipid bilayer membrane with a large
field applied to it where the hydrophilic heads create a pore and that pore can allow
ions and macromolecules to flow freely from the outside to the inside of the cell
now we've known about shock induced electroporation and injury for a long time
the experiment demonstrated here shows the effects of a 10 millisecond pulse which is a relatively
long pulse compared to what we're using in pulse field ablation on action potential amplitude dvdt
diastolic depolarization and conduction velocity and it's by creation of these pores that causes uh
depolarization of the cell and breakdown of the cell and ultimately can proceed onto cell death
now pulsed field ablation unlike rf has many parameters to be considered
the parameters are listed on the side here and i won't go into all of the details but
you can see that each particular pulse has a variety of things that can be modulated
and each pulse can be put together in a train can be monophasic or biphasic
and pulse width and amplitude and train number and air pulse distance all these things can be
adjusted and the question is what's important and what translates into safe and effective ablation
here's an experiment looking at the effect of an electrical field on an individual cell
and you can see in the first graph as the applied potential is increased at a certain inflection
point there is breakdown of the dielectric membrane and current flow begins so there is this
threshold effect that is dependent on amplitude of the field and it's dependent as you can see here
on distance from the source as well so the field falls off with increasing distance and it's this
field over distance that is the parameter that you will see in experiments on post field ablation
now how do you deliver the pulse you can deliver it just as a single
square wave pulse or you can deliver it as a biphasic pulse and you can
bunch those biphasic pulse waves closely together or you can spread them out and you can give a
series of pulses over time or a series of pulse trains over time or a continuous pulse strain now
in these experiments the total energy delivered was the same for each of these conditions
but you can see how you break the pulse up how long the pulse duration is is very uh is
very important in terms of the effect that you get so you can see with the longer pulse the
100 microsecond pulse width you get significant cell injury at a relatively lower field strength
whereas if you use trains of shorter pulses you require higher voltages to achieve the same
effect this is another meta-analysis looking at a number of studies with different pulse durations
being tested and you can see that as you increase pulse duration the membrane effect is increased
and so this is something that many studies have shown in many different tissues over time
and this is a familiar looking curve to anyone who's in the pacing field a strength duration
curve so higher amplitude shorter duration or lower amplitude long duration can achieve the same
threshold effect but you do reach asymptotic values chronoxy values and you can see in this
depiction there is a range where there is no effect
there's a range where there's a reversible effect and then you get into an irreversible effect
what about tissue heating we talk about this being a non-thermal approach and i think that that is
the um observation in most settings that if there is temperature rise it's in very very
close proximity to the right to the electrode and it's in the range usually of just a few degrees
now what other parameters can you modulate well here's an experiment in a cellular preparation
looking at a variety of different parameters and you can see 50 versus 500 volt field the higher
voltage had more effect not surprising 10 versus 20 pulses more pulses more effect if something has
a little counter-intuitive when they delivered the pulse um pulses at a two hertz frequency
versus one hertz or a four hertz frequency versus two hertz spreading out the pulses over a longer
duration had more effect where if you squeeze them all in in a shorter duration it was less effective
now one of the interesting things about cardiac tissue is that cardiac cells are people are uh
polarized they are resting at a minus 90 millivolts due to the
nernst potential and the potassium equilibrium and you can see that depending on the field
orientation to the cell and depending upon the phase you get a predominant effect on one side
of the cell or if it's biphasic you get it on both sides of the cell and in a cardiac tissue
one directionality of phase will have more electromotive
effect on the sarcolemma membrane because of the polarity of the membrane versus the other phase
effect so cardiac tissue is uh is special and and probably accounts for
its increased sensitivity to this approach now the other important factor are the field effects just
the distribution of electricity in the tissue and there are a lot of factors that go into that
unipolar versus bipolar the distance of the bipolar delivery
presence of scar connective tissue blood pool and the actual poration of the cells alters the
uh the milieu through which the electricity is transition is transited so unipolar versus bipolar
delivery with a multi-polar array you get more localized field with bipolar delivery you also
don't get as much nerve and muscle stimulation it may be better tolerated um but the lesion margins
are more predictable and follow the boundary of this field whereas the tissue conductance effects
are much more of a factor when you have unipolar delivery and how much energy is dissipated by the
dispersive electrode is important as well the inter-electrode distance interestingly as you
increase the distance between electrodes the lesion actually gets bigger and that has to do
again with field distribution and um and so you may find whereas rf we deliver
in closely spaced electrodes with with pulse field wider spacing of electrodes
might be preferable the tissue very important scar tissue has high water content lower impedance and
will allow the passage of current more readily whereas myocardium has higher impedance and more
resistance so you'll have current shunting into scar this may be a favorable or an
unfavorable effect with ablation of bt in scarred hearts and you can see the effect of
scar on water content in an infarct versus normal the water content is higher and impedance is lower
when you deliver electricity to a cell solution as you pass that current
through the cells the sarcolemma membrane breaks down and the conductivity
actually increases because the electricity blows right through the cells and you can see
in this cell solution as opposed to a comparison acellular buffer solution as you increase the
field the conductivity actually increases and so that's why a second pulse and a third pulse may
have more effect than the initial pulse and you can see here this effect as the number increases
conductivity change increases as the field increases you have increased permeabilization
and decreased survival so in the clinical setting with pulse field ablation we can see the
publication by dr reddy that uh as they iterated through various wave forms
in their in their um pilot trial and i don't think they did a lot of preclinical testing
but they tested this in humans you can see as they learned and as they altered the waveform
their success rates went up as the study continued so in conclusion pulse field ablation
irreversible electroporation is accomplished by a breakdown of the dielectric membranes by high
voltage fields efficacy of pfa is predominantly determined by field strength and pulse duration
multiple other waveform parameters also contribute to the pfa effects
and tissue factors directly impact field distribution and field strength thank you