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General Cardiology – Basic Science

Cardiology 2000;93:234–241 Received: February 7, 2000


Accepted after revision: April 27, 2000

Temperature-Controlled High Frequency


Ablation for Creation of Transmyocardial
Channels: In vivo Validation of a Novel Method
Ulrich Dietz a Mike Otto b Michael Buerke a Olaf Eick d Reza El Odhi a
Alp Förderer a Gerd Rippin c C. James Kirkpatrick b Jürgen Meyer a
Harald Darius a
a Medical Clinic II, b Institute of Pathology and c Institute for Medical Statistics and Documentation,

University Hospital, Mainz, Germany; d Medtronic, Bakken Research Center, Maastricht, The Netherlands

Key Words had a lumen patency of 62/3 of the channel. Ferret diam-
Transmyocardial revascularization W High frequency eter of the channels was 414 B 180 Ìm and of the necrot-
ablation ic zone 3,558 B 1,200 Ìm. In temperature-controlled
applications, channel dimensions were strongly in-
fluenced by the maximum tissue temperature and the
Abstract duration of energy delivery (Tmax: p = 0.0006; duration:
Objective: We investigated the feasibility and short-term p = 0.003). Channel and necrosis dimensions correlated
effects of a novel procedure to create intramyocardial better with biometric parameters in temperature-con-
channels by means of high frequency (HF) ablation in a trolled compared with power-controlled applications.
rabbit in vivo model. Methods: A flexible catheter ending Conclusion: Mechanically created transmyocardial chan-
in a cylindrical electrode (diameter 0.7 mm) with a sharp- nels can be stabilized by HF heating of the surrounding
ened tip was used for HF energy application following tissue. A high percentage of these channels remain
transmyocardial insertion. Power-controlled or energy- patent. The channel dimensions are closely correlated
controlled energy applications were performed in 16 with maximum temperature and duration of energy de-
anesthetized rabbits after thoracotomy with a follow-up livery in a temperature-controlled application mode.
for 3 h. Assessment of myocardial channels and the Copyright © 2000 S. Karger AG, Basel

necrotic zone was performed by morphometric quantifi-


cation in serial sections. The ferret diameter was used to
compare channel dimensions and the extent of necrosis. Introduction
Results: Thirty-nine power-controlled and 54 tempera-
ture-controlled HF applications were performed. The Direct myocardial revascularization procedures have
shape of identified channels was round in 71% and 69% been proposed for patients who are not suitable for any
further interventional or surgical revascularization proce-
dure because of end-stage coronary heart disease [1]. Clin-
This study was presented in part at the 71st Scientific Sessions of the ical application of laser revascularization procedures
American Heart Association 1998 and the 20th Congress of the Euro- (transmyocardial and percutaneous myocardial revascu-
pean Society of Cardiology 1998. larization) resulted in a marked improvement of symp-

© 2000 S. Karger AG, Basel Ulrich Dietz, MD


ABC 0008–6312/00/0934–0234$17.50/0 Deutsche Klinik für Diagnostik
Fax + 41 61 306 12 34 Aukammallee 33
E-Mail karger@karger.ch Accessible online at: D–65191 Wiesbaden (Germany)
www.karger.com www.karger.com/journals/crd Tel. +49 611 577 267, Fax +49 611 577 577, E-Mail kardio.dietz@dkd-wiesbaden.de
toms [2]. However, in histological analyses done in pa- system for digital image acquisition and semiautomatic area calcula-
tients who died after the procedure, the majority of chan- tion (Image Tools 1.28, University of Texas Health Science Center,
San Antonio, Tex., USA). The largest axis length, the smallest axis
nels were occluded because of scar tissue obliterating the
length and the ferret diameter, which is computed as the diameter of
channels [3, 4]. We investigated high frequency (HF) cur- a circle having the same area as the object [sqrt (4 ! area/pi)], of
rent to be used for the creation of transmyocardial chan- channels and necroses were assessed.
nels. The feasibility of HF energy application in trans-
myocardial insertions performed with a specially de- Statistics
Data were expressed as mean value B standard deviation. The
signed probe and the influence of the energy delivery
statistical significance of differences between groups was determined
mode on the histological outcome are focal points of the by the Wilcoxon test. A multivariate analysis was performed using a
present study. linear regression model. The variation coefficient (VC) was calcu-
lated by dividing the standard deviation by the mean value. Spear-
man correlation coefficient was calculated to compare continuous
variables. A p value of ^ 0.05 was regarded as statistically signifi-
Methods cant.

HF Device
The HF probe (Medtronic Bakken Research Center, Maastricht,
The Netherlands) consists of a 4-french catheter with a cylindrical Results
ablation electrode, 0.7 mm in diameter, 5 mm in length, which ends
in a sharpened tip. A thermocouple is incorporated in the center of
the ablation electrode. The device was connected to a high frequency Thirty-nine power-controlled applications were per-
generator (Atakr, Medtronic CardioRhythm, Minneapolis, Minn., formed in 8 rabbits and 54 temperature-controlled appli-
USA) for high frequency energy delivery (475 kHz) by either a tem- cations in another 8 rabbits. Energy application was
perature-controlled (TCM) or a power-controlled (PCM) mode of HF
aborted prematurely during 9 applications because of an
energy delivery. Energy delivery was automatically aborted when the
impedance was less than 50 ø or exceeded 250 ø. The HF power, the impedance exceeding 250 ø. Bleeding after removal of
ablation temperature and the impedance were recorded during ener- the HF device occurred in all applications and was
gy delivery. stopped by manual compression. One animal died 1 h
after the intervention because of heart failure due to a
Animals Procedure
large anterior wall myocardial infarction. This was caused
Animals were cared for according to the Principles of Laboratory
Animal Care. The experimental protocol was reviewed by the institu- by an application next to the left anterior descending
tional animal rights’ committee. artery resulting in a proximal occlusion of the vessel. In all
Sixteen adult rabbits, weighing 3.8 B 0.3 kg, were anesthetized other animals, heart rate and systemic blood pressure
with an intravenous injection of thiopental sodium. Animals were were unchanged with respect to preinterventional values.
intubated and mechanically ventilated while midsternal thoracoto-
Experiments were terminated after 205 B 35 min. Mac-
my and pericardiotomy were performed. The ablation electrode was
inserted transmurally at the anterior wall. Five to seven insertions roscopically, the puncture holes at the epicardial surface
following HF energy application were performed in each animal. HF were surrounded by a circular necrotic area in 56% of
energy applications were performed by one of two different modali- applications (fig. 1).
ties: (1) the PCM or (2) the TCM. In PCM applications, the power
output was fixed ranging from 2 to 30 W with incremental steps of
Biometric Data
2 W. Applications utilizing the TCM were performed with a preset
target temperature between 55 and 90 ° C with incremental steps of Power-Controlled Applications. In the PCM, the mean
5 ° C. The duration of HF applications was limited to 3, 6 or 10 s in power output was 14 B 8 W with an applied energy
both modalities. between 6 and 225 J and a mean of 82 J. The measured
Hemodynamic monitoring was continued for 3 h. Thereafter, a maximum tissue temperature was 73 B 13 ° C. Impe-
bolus of thiopental was administered for euthanasia. The hearts were
dance was 169 B 33 ø.
excised and coronary arteries were perfused by 4% buffered formal-
dehyde. Pieces of the ventricular wall containing the transmyocardial In general, a higher power output resulted in a higher
channels were excised. Fixation was completed in a bath of buffered tissue temperature, but the maximum tissue temperature
formaldehyde for 5 days at 4 ° C. was not associated with the power output (r = 0.2) or the
energy delivered (r = 0.32). The slope of the temperature
Tissue Preparations and Analysis
curve as well as the maximum temperature reached var-
Serial sections, each 5 Ìm thick, of paraffin-embedded myocar-
dial pieces were stained with hematoxylin/eosin (HE) and fuchsin for ied widely for an identical power output (fig. 2a). Six
qualitative and quantitative analysis of the channels and necrotic applications resulted in a tissue temperature of less than
zones, respectively. Histomorphometry was done using a calibrated 55 ° C.

HF Transmyocardial Revascularization Cardiology 2000;93:234–241 235


in vivo
Temperature-Controlled Applications. In the TCM,
mean maximum tissue temperature measured 69 B
10 ° C. The power output which was adjusted automatical-
ly by the generator was on average 13 B 6 W with a deliv-
ered energy between 9 and 192 J and a mean of 67 J.
Impedance was 185 B 30 ø. The preset temperature was
reached within 1.5 s in all instances, which was achieved
by a high initial power output. The power output to main-
tain the temperature was much lower but varied widely

Fig. 1. Epicardial site of rabbit myocardium after application of HF


energy delivery using the PCM with a power output of 12 W and
maximum tissue temperature of 73 ° C. In the center, a hole can be
recognized which is surrounded by a circular zone of denatured tis-
sue.

Fig. 2. a Recording of tissue temperature


response in 4 power-controlled applications,
all of which were performed with a power
output of 20 W. b The tissue temperature
and the corresponding power output of 3
temperature-controlled applications with a
preset temperature of 65 ° C are depicted.
Note that in the PCM the temperature re-
sponse differs, while the power output is
identical. In the TCM, initially a high power
output is adjusted automatically by the gen-
erator, but the power output necessary to
maintain the tissue temperature differs for
these 3 applications.

236 Cardiology 2000;93:234–241 Dietz/Otto/Buerke/Eick/El Odhi/Förderer/


Rippin/Kirkpatrick/Meyer/Darius
Fig. 3. Myocardial specimen containing a
cross section of a channel created by power-
controlled HF energy delivery with a maxi-
mum tissue temperature of 75 ° C and a du-
ration of 10 s. The central channel is sur-
rounded by a necrotic zone which is delin-
eated from intact myocardium by a hypereo-
sinophilic band (arrows). The channel has an
ovaloid shape and is obstructed by less than
one third by debris (*). Note that the vessels
located within the necrotic zone (arrow-
heads) show no morphological alterations.
HE. !560.

Fig. 4. Myocardial specimen containing a


cross section of a channel created by temper-
ature-controlled HF energy delivery with a
temperature of 75 ° C and a duration of 6 s.
The channel has an oval shape without any
obstructive material. The surrounding tissue
shows moderate hemorrhage. The necrotic
area is demarcated by a typical dense fuchsi-
nophilic band (arrows). Fuchsin. !280.

between the applications using the temperature-con- were present in 62 applications. No quantitative assess-
trolled mode (fig. 2b). ment was performed in 5 channels because they were cut
Comparison of Energy Delivery Modes. The slope of in a longitudinal direction. In 14 applications, channels
the tissue temperature response exhibited a greater varia- could not be clearly delineated or a procedure-related
tion in the PCM as compared to the TCM (VC 0.7 vs. 0.2, cause of tissue discontinuity was not certain, and in 12
p = 0.001). applications no channel was recognizable by histology.
The channel shape was round to oval in 71% or flat-
Histological Findings tened in 29% of sections (fig. 3). Channel lumen was
Analysis of channels was performed in 905 sections obstructed by ^1/3 in 16%, 11/3 but ^2/3 in 45%, more
stained with HE. Channels created by the HF device than 2/3 in 31%, and without any obstruction in 8%.
could be identified in 81 of 93 applications. Cross sections Obstructive material consisted of fresh thrombus in 94%
of channels allowing qualitative and quantitative analysis and cellular debris in 61%.

HF Transmyocardial Revascularization Cardiology 2000;93:234–241 237


in vivo
Fig. 5. Scatter plots and regression of the fer-
ret diameter and the corresponding tempera-
ture-time product. A close relation is present
in temperature-controlled (a) but not in
power-controlled (b) applications.

Quantitative assessment of channel dimensions was tions and was 3,320 B 1,180 Ìm (1,485–5,920 Ìm) for
performed in sections of 32 TCM applications and in TCM applications. The area of the necrotic zone mea-
those of 30 PCM energy deliveries. The overall channel sured 11 B 6.8 mm2 for all measurements. The ferret
area was 0.22 B 0.17 mm2, the smallest channel axis diameter of the channels was correlated with the round-
amounted to 290 B 140 Ìm and the largest to 960 B ness of the channel (r = 0.43, p = 0.0019). No other signifi-
380 Ìm. The ferret diameter ranged from 80 to 1,254 Ìm cant correlations between binary qualitative and quanti-
with a mean of 371 B 144 Ìm for the PCM applications tative histological parameters were found.
and from 79 to 1,130 Ìm with a mean of 460 B 200 Ìm
for the TCM applications. Quantitative assessment of the Influence of Biometric Parameters
necrotic zone was done in 167 sections stained with fuch- The tissue temperature was higher in channels with a
sin (fig. 4). The ferret diameter of the necrotic zone was round or oval geometry than in those which were flat (74
4,460 B 1,460 Ìm (1,960–7,170 Ìm) for PCM applica- B 12 vs. 69 B 12 ° C, p = 0.001). Channel dimensions

238 Cardiology 2000;93:234–241 Dietz/Otto/Buerke/Eick/El Odhi/Förderer/


Rippin/Kirkpatrick/Meyer/Darius
Fig. 6. The ferret diameter of the necroses
and the maximum tissue temperature are
closely related in the temperature-controlled
application (a) but not in the application
using the power-controlled energy delivery
mode (b).

correlated closest with the duration of a tissue temperature but not with the energy delivered; no such correlation was
between 60 and 70 ° C (largest axis, r = 0.56; smallest axis, found for channels created by TCM applications.
r = 0.63; ferret diameter, r = 0.62; p !0.0002 for all values). Dimensions of the necrotic zone were correlated with
Correlation was less for the duration of tissue temperature the tissue temperature (largest axis, r = 0.61; smallest axis,
between 50 and 60 ° C, or exceeding 70 ° C (data not r = 0.62; ferret diameter, r = 0.65; p = 0.0001 for all val-
shown). The channel ferret diameter in TCM applications ues) for values of TCM applications, which also correlated
correlated with the temperature-time product (r = 0.60, p = with the duration of the tissue temperature exceeding
0.003) and the maximum tissue temperature (r = 0.53, p = 70 ° C (r = 0.58, r = 0.59 and r = 0.60, respectively, for all
0.0018), whereas channel dimensions created in PCM did p ! 0.0002), whereas necrosis dimensions of PCM appli-
not correlate with these parameters (fig. 5). cations were not correlated with these parameters (fig. 6).
The channel ferret diameter after PCM applications Dimensions of the channels and necroses were not corre-
correlated with the power output (r = 0.53, p = 0.0025), lated with other biometric parameters.

HF Transmyocardial Revascularization Cardiology 2000;93:234–241 239


in vivo
Linear regression analysis revealed that the maximum cessfully used for endocardial tissue ablation [14, 15]. It
tissue temperature [probability of estimate (PE) 6.3, stan- was intended that the present investigation should answer
dard error of the estimate (SE) 3.2–10.1, p = 0.0006] and 3 questions: (1) is it feasible to create transmyocardial
the duration of energy delivery (PE 29, SE 14.6–43.2, p = channels by HF energy delivery? (2) is it possible to iden-
0.0003) were independent predictors for the dimension tify the channels histologically?, and (3) which energy
of the channel ferret diameter in TCM applications. For delivery mode results in the best reproducible tissue
values obtained in PCM applications, no dependency of effect, to serve as a prerequisite for a possible clinical
the ferret channel diameter on biometric parameters application?
could be demonstrated. The maximum tissue tempera- The feasibility of this procedure could be clearly dem-
ture was predictive for the ferret diameter of the necrotic onstrated in this series of experiments. An incomplete
zone (PE 85, SE 53–117, p = 0.0001) for values of both transmyocardial placement of the catheter caused an
application modes. No independent influence on necro- abortion of the energy delivery process automatically,
sis dimensions was found for the duration of the energy which was a rare incident. Global left ventricular function
delivery or for the other parameters by linear regression was not impaired, despite the fact that a rather large myo-
analysis. cardial area was treated. In 1 animal an anterior wall
infarction developed due to an unintentional misplace-
ment of the device, which resulted in a thrombotic LAD
Discussion occlusion.
In this study, we were able to demonstrate convincing-
Numerous efforts have been made to restore myocar- ly that mechanically generated channels stabilized by HF
dial blood supply by an alternative route to the coronary heating of the surrounding tissue stay patent in a high per-
artery system in patients with end-stage coronary heart centage of cases at least for a short period of time. The
disease. In the early 1960s, needle acupuncture of the hypothesis that tissue denaturation is needed to prevent
myocardium to achieve a nutritive blood flow from the channels from collapsing was supported by the finding
left ventricular cavity was investigated [5, 6]. However, that with maximum tissue temperature below 55 ° C no
due to the architecture of the ventricular myocardium the open channels could be identified. In all channels identi-
channels occluded rapidly with the exception of channels fied, some signs of severe cell destruction next to the chan-
created by a needle with a 4-mm diameter [7]. Laser was nels were visible microscopically.
also instituted to create channels by vaporization of myo- Histologically, channels differed with respect to their
cardium [8, 9]. Although short-term patency could be doc- cross-sectional geometry and surface. In order to be able
umented for some of the channels, most investigations to compare channel dimensions, the ferret diameter was
failed to show long-term patency [10, 11]. calculated, which has been shown to be superior to other
We hypothesized that tissue modulation by generation parameters in the quantification of objects with irregular
of a local thermal injury can stabilize mechanically contours, although being a virtual parameter [16]. To
created intramyocardial channels and thereby prevent determine the impact of the duration of tissue heating, the
early occlusion. The aim of our study was to evaluate product of energy delivery duration and mean tempera-
whether HF current can be used to achieve a predictable ture was calculated, thereby integrating the temperature
tissue denaturation surrounding mechanically created over time. This parameter exhibited the closest correla-
channels. HF current results in resistive heating of tissue tion to the channel’s ferret diameter, suggesting that the
which is in immediate contact with the active electrode stability of the channels may depend on the duration of
where the current density is much higher compared to the exposure to a given temperature. This assumption was
large indifferent electrode. The current density decreases supported by the results of a linear regression model.
by the square of the distance, and the temperature de- In contrast to the results of the channel analysis, the
creases by the fourth of the distance. Thus, a rapid and extension of the necrotic zone was correlated with the
well-controlled heating of tissue adjacent to the ablation maximum tissue temperature. There was no dependency
electrode can be achieved. Irreversible damage to the found for the duration of tissue heating. These results con-
myocardium has been documented for HF energy appli- firm previous findings of other investigators [12] and can
cations, if the myocardium is heated up to more than be most likely explained by heat convection to the vascu-
50 ° C [12, 13]. Both the power-controlled and the temper- lature. Therefore, an extended period of heat application
ature-controlled energy delivery modes have been suc- would not enlarge the necrotic zone. No relation was

240 Cardiology 2000;93:234–241 Dietz/Otto/Buerke/Eick/El Odhi/Förderer/


Rippin/Kirkpatrick/Meyer/Darius
found between the extent of the necrotic zone and the mode seems to be superior to the PCM with respect to the
channel dimensions, suggesting that the maintenance of reproducibility of the biometric data and the histological
channels can be achieved even by a small necrotic rim outcome.
that is able to withstand the compressing shear forces of
the contracting myocardium.
The last question to be answered is related to the mode Conclusion
of energy delivery. Surprisingly, the temperature response
in power-controlled applications varied widely despite an Transmyocardial channels can be created by insertions
identical power output. In temperature-controlled appli- with a 0.7-mm probe and denaturation of the surrounding
cations, the preset temperature was kept constant due to tissue by heating using HF energy applied by a newly
the automatic adjustment of the power output. The most designed catheter. A reproducible tissue temperature can
likely reason for this variation may be differences in heat be achieved in the TCM, which requires a thermocouple
convection in the immediate vicinity of larger vessels. within the tip of the probe. By these means, intramyocar-
The duration of HF delivery required to achieve tissue dial channels can be created and a high percentage of
temperatures exceeding 55 ° C was shorter in TCM as these channels remains patent. Both, the tissue tempera-
compared to PCM applications. This was due to an initial ture and the duration of heating determine the dimen-
higher power output automatically adjusted by the gener- sions of the resulting channels. The extent of the sur-
ator in the TCM. The lower correlation between the chan- rounding necrosis is small and depends on the maximum
nel ferret diameter and the temperature time product in tissue temperature. Thus, reproducible transmyocardial
PCM applications may in part be explained by these find- channels with a small predictable necrotic zone can be
ings. Thus, the temperature-controlled energy delivery achieved by using a temperature-controlled HF device.

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in vivo

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