Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
CA 02305333 2000-03-31
WO 99/17671 PCT/US98/20799
TRANSMYOCARDIAL REVASCULARIZATION
USING RADIOFREQUENCY ENERGY
RELATED APPLICATIONS
This application is a continuation-in-part of copending application Serial No.
08/942,874, filed October 2, 1997, and application Serial No. 08/968,184,
filed
November 12, 1997, which are both continuations of application Serial No.
08/517,499, filed August 9, 1995. All of the above-referenced applications are
hereby incorporated by reference in their entirety.
BACKGROUND OF THE INVENTION
This invention is directed to the ablation or disruption of tissue in the wall
of a
patient's heart and particularly to form channels within the heart wall in
order to
perform transmyocardial revascularization (TMR), to deliver therapeutic or
diagnostic agents to various locations in the patient's heart wall or for a
variety of
other utilities.
As presently used, TMR involves forming a plurality of channels in a
ventricular wall of a patient's heart by means of laser energy. The first
clinical trials
of the TMR procedure using laser energy were performed by Mirhoseini et al.
See
for example the discussions in Lasers in General Surgery (Williams & Wilkins;
1989), pp. 216-223. Other early disclosures of the TMR procedure are found in
an
article by Okada et al. in Kobe J. Med. Sci 32, 151-161, October 1986 and in
U.S.
Patent 4,658,817 (Hardy). These early references describe intraoperative TMR
procedures which require an opening in the chest wall and include formation of
channels completely through the heart wall starting from the epicardium.
CA 02305333 2000-03-31
WO 99/17671 PCT/US98/20799
2
U.S. Patent N0. 5,554,152 which issued on December 20, 1994 {Aita et al.),
which is incorporated herein in its entirety, describes a system for TMR which
is
introduced through the chest wall either as an intraoperative procedure where
the
chest is opened up or as a minimally invasive procedure where the system is
introduced into the patient's chest cavity through small openings in the chest
by
means of a thoroscope.
In U.S. Patent No. 5,389,096 (Aita et al.) a percutaneous TMR procedure is
described wherein an elongated flexible laser based optical fiber device is
introduced through the patient's peripheral arterial system, e.g., the femoral
artery,
and advanced through the aorta until the distal end of the device extends into
the
patient's left ventricle. Within the left ventricle, the distal end of the
optical fiber
device is directed toward a desired location on the patient's endocardium and
urged
against the endocardial surface while a laser beam is emitted from its distal
end to
form the channel.
Copending application Serial No. 081078,443, filed on June 15, 1993 (Aita et
al.), which is incorporated herein in its entirety, describes an intravascular
system
for myocardial revascularization which is percutaneously introduced and
advanced
into the left ventricle of the patient's heart where laser energy initiates
revascularization through the endocardium and into the myocardium. This
procedure eliminates the need of the prior procedures to open the chest cavity
and
to penetrate the epicardium in order to form the channel through the
endocardium
into the myocardium.
The laser based revascularization procedure has been shown to be clinically
beneficial to a variety of patients, particularly patients who were, for the
most part,
CA 02305333 2000-03-31
WO 99/17671 PCT/US98/20799
3
not suitable candidates for by-pass surgery or for minimally invasive
procedures
such as angioplasty or atherectomy. However, to date the equipment for laser
based systems has been quite expensive. What has been needed is a system
which is less expensive than but as clinically effective as laser based
systems. The
present invention satisfies these and other needs.
SUMMARY OF THE INVENTION
The present invention is directed to a method and system for the
revascularization of a region of a patient's heart by ablating or disrupting
tissue in
said region with emissions of radiofrequency (RF) energy and is particularly
directed to the methods and systems to ablate or disrupt tissue in the
patient's heart
wall to form channels therein by means of such RF energy.
One method includes the step of inserting an elongated shaft having an RF
energy emitter into a patient's vasculature. Preferably, a system for guiding
the
device is also provided. The RF energy emitter is guided to the interior of
the left
ventricle and positioned against a desired portion of the ventricle's inner
wall.
Then, the RF energy emitter is activated to remove or otherwise injure tissue.
The
RF energy emitter may be advanced so as to remove tissue until a channel or
disrupted area is formed to the desired depth. Methods for controlling the
depth of
channel formation include fluoroscopic or ultrasonic visualization or
advancing the
revascularization means a fixed distance. In addition, penetration limitation
can be
achieved with mechanical penetration limiters such as those taught in
copending
U.S. Application Ser. No. 08/486,978, which is hereby incorporated by
reference in
its entirety. The RF energy emitter is repositioned against another portion of
the
CA 02305333 2000-03-31
WO 99/17671 PCT/US98/20799
4
heart wall and the process is repeated until enough channels or regions of
ablated
tissue are formed to provide the desired revascularization.
In accordance with one embodiment of the invention, tissue is ablated within
a patient's heart wall by means of one or more bursts of RF emissions over
intervals of about one to about 500 msec and preferably about 30 to about 130
msec. A radiofrequency burst may comprise a continuous emission or
discontinuous emission, i.e. be pulsatile, and, if pulsatile, may involve a
plurality or
train of pulses which may or may not be of the same width (duration),
frequency or
amplitude.
The RF emissions are preferably controlled so that heart tissue is exposed to
the RF energy over a desired period and particularly over a period which will
avoid
interfering with the patient's heart beat, e.g., just after the R wave but
before the T
wave. One to about 10 bursts of RF energy may be required to effectively form
the
desired channel within the patient's heart wall and preferably one burst of RF
emission is delivered per heart cycle. The RF energy source generally should
have
a peak power output of about 150 to about 500 watts, preferably about 200 to
about
300 watts.
It also may be desirable to operate the RF energy emitter at more than one
energy level. Initially, the channel formation or tissue disruption may be
performed
at a relatively high energy level to position and anchor the RF ablation
device. For
greater control, the remainder of the procedure may be performed at a lower
energy
level.
One presently preferred system for revascularizing a patient's heart wall
includes an RF energy transmitting member which has a proximal end, and an
CA 02305333 2000-03-31
WO 99/17b71 PCT/US98/20799
uninsulated distal tip configured to emit RF energy. The system is introduced
into
the patient and advanced within the patient until the uninsulated distal tip
thereof is
disposed adjacent to a surface of the patient's heart wall. At least one burst
of RF
energy from an RF energy source is transmitted through the RF energy
transmitting
5 member to the uninsulated distal tip thereof. The RF energy is then emitted
from
the distal tip and into the heart wall in contact with said distal tip. In
preferred
embodiments, the channel formed in the heart wall preferably has an aspect
ratio,
i.e., depth to width, of at least 1, preferably at least 2.
Any particles of tissue produced by the RF energy emitter have the potential
to create emboli if allowed to escape into the patient's circulatory system.
Accordingly, in a number of these embodiments, the RF energy emitter includes
lumens for perfusion and aspiration to remove the particles from the patient's
body.
Alternatively, the RF energy emitter is configured to produce particles small
enough
to safely propagate through the smallest branches of the patient's
vasculature,
approximately 6-10 Nm in diameter.
One embodiment of the invention utilizes a percutaneous approach in which
a flexible RF energy emitter is advanced through the patient's vasculature
until a
distal portion of the system enters a heart chamber such as the left
ventricle. The
RF energy transmitting member is advanced so that the uninsulated distal tip
which
emits RF energy contacts the interior surface of the heart wall which defines
in part
the heart chamber. At least one burst of RF energy is emitted from the
uninsulated
distal tip of the system into the patient's heart wail wherein tissue is
ablated or
otherwise disrupted, resulting in the revascularization of the heart wall
region.
Another embodiment of the invention involves a minimally invasive approach
CA 02305333 2000-03-31
WO 99/17671 PCT/US98/20799
6
where a small incision is made in the patient's chest and with or without the
benefit
of a trocar sheath, an elongated RF energy transmitting member is advanced
into
the patient's chest cavity until the uninsulated distal tip of the RF
transmitting
member contacts the exterior of the patient's heart. One or more bursts of RF
energy are emitted from the uninsulated distal tip so as to ablate or disrupt
tissue
within the patient's heart wall causing the revascularization thereof, as in
the
previously discussed embodiments of the invention. A similar procedure may be
used in conjunction with an open chest procedure such as coronary by-pass
surgery or in other surgical procedures, as is the case with laser based
transmyocardial revascularization.
The RF energy emitter preferably includes an RF energy transmitting
member which is insulated along its length except for the distal tip thereof
which is
uninsulated and which is configured to contact the surface of the heart wall
and to
emit bursts of RF energy therefrom into adjacent tissue of the heart wall. The
uninsulated distal tip can have a diameter of about 0.025 to about 0.2 inch
(0.64-5.1
mm), preferably about 0.04 to about 0.08 inch (1-2 mm) and a length of about
0.1 to
about 5 mm, preferably about 1.5 to about 3.5 mm. The distal tip may be solid
or
hollow and may be relatively sharp or blunt. However, it should not be sharp
enough to penetrate the tissue of the heart wall when pressed against the wall
to
maintain contact during the emission of RF energy bursts. The average power
level
should be about 50 to about 500 watts, preferably about 100 to about 300
watts.
The frequency of the RF current should not be less than 100 kHz and preferably
is
about 250 to about 500 kHz.
The method and system of the invention effectively ablates or disturbs tissue
CA 02305333 2000-03-31
WO 99/17671 PCT/US98/20799
7
within the patient's heart wall to revascularize the ablated region and
particularly can
be used to form channels within the heart wall. These and other advantages of
the
invention will become more apparent from the following detailed description of
the
invention and the accompanying exemplary drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a schematic illustration of a system for revascularizing heart
tissue
which embodies features of the invention.
FIG. 2 is a transverse cross-section of the RF energy transmitting member of
the system shown in F1G. 1 taken along the lines 2-2.
FIG. 3 is a schematic illustration of the one shot shown in FIG. 1.
FIG. 4 is a schematic illustration of a system for generating trigger signals
based upon the patient's heart beat.
FIG. 5 is an elevational view of a delivery system for the RF energy emitter
for positioning the operative distal end thereof adjacent to the endocardium
of a
patient's heart wall.
FIG. 6 is a schematic elevational view, partially in cross-section, of a human
heart showing revascularization of the myocardium according to the invention.
FIG. 7 is a schematic longitudinal cross-sectional view of the distal portion
of
a deflectable elongated RF system which embodies features of the invention.
FIGS. 8 and 9 are schematic longitudinal cross-sectional views of RF
systems useful in the practice of this invention.
CA 02305333 2000-03-31
WO 99/17671 PCTIUS98/20799
8
DETAILED DESCRIPTION OF THE DRAWINGS
FIGS. 1 and 2 depict an RF system 10 embodying features of the invention
which includes an RF energy transmitting member 11 having a proximal end
configured for electrical connection to a source 12 of RF energy and an
uninsulated
exposed distal end 13 which is configured to emit pulsed RF energy received
from
the source and transmitted through the RF energy transmitting member. The RF
energy transmitting member 11 includes an electrical conductor 14 which may be
hollow or solid, a single or multiple strand and an insulating jacket 15
formed of
suitable insulating polymeric material. A suitable source of RF energy is the
Excaliber RF Generator from Aspen Laboratories (ConMed, Englewood, CO, USA).
The output from the RF energy source 12 is pulsed by pulse-trigger system
16 which includes a one-shot 17, such as CD4047 sold by National
Semiconductor,
configured to receive trigger signals 18 through electrical conductor 19 and
generate in response a pulsed output signal 20 connected to a NPN transistor
21.
The pulsed output signal 20 from the one-shot 17 actuates the transistor 21
for the
duration of the output signal. The output of the transistor 21 is connected to
reed
relay 22 which is configured to close upon receiving the output from the
transistor
21. The output of the reed relay 22 is connected in series to the foot switch
23.
When the foot switch 23 is closed and reed relay 22 is closed, the RF energy
source is actuated to emit RF energy for the duration of the output of the
reed
relay 22.
FIG. 3 illustrates in more detail the one-shot shown in FIG. 1 which has 14
pins, identified as pins a-n in FIG. 3. The one-shot shown in FIG. 3 has the
pins
designated with letters a-n to avoid confusion with other reference numbers
used
CA 02305333 2000-03-31
WO 99/I7671 PCT/US98/20799
9
herein. The one-shot model number CD4047 has these pins numbered 1-14. The
trigger signal 18 from an ECG unit is received by pin h and upon receipt of
the
trigger signal an on signal is emitted from pin j. The duration of the on
signal from
pin j is controlled by the resistance R and capacitance C from the RC circuit
connected to pins a-c as shown. The resistance R can typically range from
about
0.1 to about 1 meg ohm and the capacitance can typically range from about 0.08
to
about 0.12 microfarads to control the duration of the pulses of output signal
20 from
about 50 to about 300 msec.
FIG. 4 schematically illustrates a system of generating trigger signals 18
based upon the patient's heart cycle 30. The signals from the patient's heart
31 are
detected with a conventional ECG unit and the detected signals are transmitted
to a
trigger generating system 32 which may also be contained in the ECG unit. The
trigger signal generating system 32 is preprogrammed to emit one or more
trigger
signals 18 at a predetermined time between the R and the T wave of the heart
cycle
30.
Reference is made to FIG. 5 which illustrates a system for the percutaneous
delivery of an RF system which has an outer catheter 40, a shaped distal end
41, a
port 42 in the distal end of the outer catheter and an inner lumen extending
within
the outer catheter to the port in the distal end. This system also includes an
inner
catheter 44 which is slidably and rotatably disposed within the inner lumen of
the
outer catheter 40 and which has a shaped distal section 45, a distal end 46, a
port
47 in the distal end of the inner catheter and an inner lumen 48 extending
therein to
the port in the distal end. An RF energy emitter 50 is slidably disposed
within the
inner lumen of inner catheter 44. The distal section 45 of the inner catheter
44 is at
CA 02305333 2000-03-31
WO 99/17671 PCT/US98/20799
an angle with respect to the main shaft section 51 of the inner catheter to
orient the
RF energy emitter 50 extending out the distal end of the inner catheter. In
this
manner the disposition of the distal end 52 of the RF energy emitter 50 can be
controlled by raising and lowering and rotation of the RF energy emitter
within the
5 inner lumen of the inner catheter 44 and the inner catheter within the inner
lumen of
the outer catheter 40. The distal end 52 of the RF energy emitter 50 is thus
pointed
in a desired direction to the endocardium defining the left ventricle 53.
Longitudinal
and rotational movement of the inner catheter 44 provides access to a large
region
of the endocardium.
10 Referring to FIG.6, the present invention also comprises a method for
revascularizing the myocardium 54 of a human heart 56. An RF system 10
including
an elongated shaft 60 with an RF energy emitter 50 disposed at the distal end
is
inserted into the vasculature of a patient, generally through one of the major
vessels by the conventional Seldinger technique. The RF energy emitter 50 is
advanced into the left ventricle 53 and positioned against a desired portion
of the
heart muscle 62 in need of increased blood circulation due to cardiovascular
disease. The RF energy emitter 50 is activated and urged against the muscle 62
to
effect removal of tissue, forming the revascularization channel 64. The tissue
region disturbed or ablated should extend a desired distance through the
endocardium 66 and into the myocardium 54 without perforating the epicardium
68.
The RF energy emitter 50 is deactivated, withdrawn from channel 64 and
repositioned against another portion of muscle 62.
In another method of the invention (not shown) an RF system 10 having an
RF energy emitter 50 on the distal end is introduced through a small opening
in the
CA 02305333 2000-03-31
WO 99/17671 PCT/US98/20799
11
patient's chest wall. RF system 10 is advanced until the RF energy emitter 50
is
positioned against the ischemic portion of the heart muscle 62. The RF energy
emitter 50 is activated and urged towards the muscle 62. Tissue is removed
sequentially from the epicardium 68, the myocardium 54 and the endocardium 66
to
form the revascularization channel 64 into the left ventricle 53. As above,
the RF
energy emitter 50 is then deactivated, withdrawn from the muscle 62 and
repositioned. In either method, the operator repeats the process until a
sufficient
number of channels 64 or similar revascularization sites are formed in muscle
62 to
treat the ischemic condition.
In operation, the RF energy emitter 50 may be maintained in position on the
heart muscle 62 by a controlled advance and gentle pressure, to insure that
the RF
energy emitter 50 is not dislodged during formation of the channel.
Alternatively,
the RF energy emitter 50 can be maintained in place by applying a vacuum at
the
distal tip thereof.
In embodiments where the RF energy emitter 50 allows rapid, intermittent
switching between active and inactive states, the operation may be
synchronized
with the patient's heart cycle to avoid channel formation during the
vulnerable
period of the heart cycle. Preferably, the RF energy emitter 50 is subject to
automatic control means which prevents operation during the T-wave portion of
the
ECG, as known in the art.
Additionally, the RF energy emitter 50 may operate at two or more energy
levels. Preferably, the initial tissue removal to penetrate the endocardium 66
is
performed at a relatively high energy level. The rapid channel formation at
this
energy level helps anchor the RF energy emitter 50 within the channel 64. The
CA 02305333 2000-03-31
WO 99/17671 PCT/US98/20799
12
remainder of the tissue removal may be performed at a lower energy level to
provide slower channel formation and greater control.
In the embodiment depicted in F1G. 2, a plurality of control lines 70 are
connected at their distal ends to the distal end 72 of shaft 60 such as by
adhesive
bonding. Adhesive bonding may utilize any of a variety of adhesives, including
cyanoacrylate. At least two, and preferably four, control lines 70 are thus
axially,
and preferably symmetrically, disposed about shaft 60. Axial movement of
control
lines 70 will thus change the angle of deflection of distal end 72 of shaft 60
with
respect to its proximal end. A mechanism (not shown) such as a ring or knob
may
be attached to the proximal ends of control lines 70 to allow manipulation of
control
lines 70. Control lines 70 are preferably approximately 3-mil stainless steel
wire,
but may be similar filaments, such as nylon, or other suitable materials
having
appropriate tensile strength.
In addition, an outer tubular member 74 preferably encloses control lines 70
and shaft 60, forming a protective covering. Outer tubular member 74 is
secured at
its distal end to distal end 72 of shaft 60, rearward of RF energy emitter 50.
In
order to facilitate precise control of the tip during the procedure, control
lines 70 are
routed through spaced apart channels 76 that are attached to the outer surface
of
shaft 60. Channels 76 are preferably constructed of 30 gauge polyamide tubing.
Control lines 70 are thus guided to remain both separated and within well
controlled
areas on the exterior of shaft 60, thus allowing for the accurate guidance of
the
RF system 10 through the remote manipulation of control fines 70.
Another means for guiding shaft 60 and RF energy emitter 50 into a proper
position within the heart is to place the shaft 60 within a deflectable
guiding catheter
CA 02305333 2000-03-31
WO 99/17671 PCT/US98/20799
13
having dual axis steerability, for an added degree of steerability and
control. Co-
pending application, S.N. 08/438,743 filed May 10, 1995, entitled DELIVERY
SYSTEM AND METHOD FOR MYOCARDIAL REVASCULARIZATION discloses
such a system and is hereby incorporated in its entirety by reference thereto.
In
practice, the positioning of the device may be viewed by esophageal ultrasound
imaging, trans-thoracic ultrasound imaging and trans-thoracic fluoroscopic
imaging.
Accordingly, it may be desirable to add one or more radiopaque marker bands to
the distal end 72 of shaft 60, for fluoroscopic imaging. RF energy emitter 50
may
thereby be aimed and controlled for forming channels fi4 in the myocardium 54
of
the ischemic heart muscle 62.
Alternative means of ablation are suitable, including thermal and other
radiation means. For example, FIG. 8 illustrates the distal portion of an RF
system
100 which has a thermal ablator 78. The thermal ablator 78 has an electrode 80
wrapped around thermally-conductive . probe 82 and extending the length of the
system 100. The diameter of probe 82 should be from about 1.0 to 5.0 mm. The
proximal ends of the electrode 80 is are connected to a radiofrequency
generating
means (not shown). Applying radiofrequency energy at suitable frequency and
power through electrode 80 produces resistive heating transmitted through
probe
82. Generally, energy from about 30 MHz to about 10 GHz is suitable to
generate
sufficient heat at probe 82 to ablate heart tissue.
Radiofrequency energy may also provide inductive heating as shown in
FIG. 9. The distal portion of ~an RF system 10 has a ferrite probe 84 on the
end. A
radiofrequency generating means (not shown) irradiates the patient's body with
energy at a frequency to which body tissue is relatively transparent but the
ferrite
CA 02305333 2000-03-31
WO 99/17671 PCT/US98/20799
14
Radiofrequency energy may also provide inductive heating as shown in F)G. 9.
The
distal portion of an RF system 10 has a ferrite probe 84 on the end. A
radiofrequency generating means (not shown) irradiates the patient's body with
energy at a frequency to which body tissue is relatively transparent but the
ferrite
probe readily absorbs, generating ablating heat.
EXAMPLE
Eighteen channels were made in the heart of a live, anesthetized medium
size dog by means of pulsed RF energy. The wattage and the size and type of
distal tip of the RF delivery system were varied to determine the nature of
the
CA 02305333 2000-03-31
WO 99/17671 PCT/US98/20799
channels formed which result from such variations. The results are set forth
in the table below.
WATTAGE DISTAL TIP UNINSULATED PULSE # OF
TYPE LENGTH DURATION PULSES
200 watts Hollow 0.05 inch 100 msec 6
200 watts Hollow 0.05 inch 100 msec 5
200 watts Hollow 0.05 inch 100 msec 5
200 watts Hollow 0.05 inch 100 msec fi
200 watts Hollow 0.05 inch 100 msec 5
200 watts Hollow 0.05 inch 100 msec 5
300 watts Hollow 0.05 inch 100 msec 3
300 watts Hollow 0.05 inch 100 msec 4
300 watts Hollow - 0.05 inch 100 msec 4
300 watts Hollow 0.05 inch 100 msec 5
300 watts Hollow 0.05 inch 100 msec 4
300 watts Hollow 0.05 inch 100 msec 5
300 watts Solid 0.15 inch 100 msec 4
300 watts Solid 0.15 inch 100 msec 5
300 watts Solid 0.15 inch 100 msec 6
300 watts Solid 0.15 inch 100 msec 7
300 watts Solid 0.15 inch 100 msec 5
300 watts Solid 0.15 inch 100 msec 5
CA 02305333 2000-03-31
WO 99/17671 PCT/US98/20799
16
Those skilled in the art will recognize that various changes can be made to
the invention without departing from the scope thereof. There has been
described
herein various systems and methods for myocardial revascularization employing
an
elongated revascularization device. The revascularization may be performed
from
within the left ventricle or from the exterior of the heart. Various
modifications to the
present invention will become apparent to those skilled in the art from the
foregoing
description and accompanying drawings. Accordingly, the present invention is
to
be limited solely by the scope of the following claims.
