Abstract
The invention relates to an ablation catheter for treatment of a patient's tissue by delivery of high-voltage pulses comprising a catheter shaft and an ablation portion being arranged at a distal end of the catheter shaft with a plurality of electrodes accommodated along the ablation portion, wherein the ablation portion forms a spiral and comprises a first loop section and a neighboring second loop section, wherein an inner diameter of the first loop section increases towards an inner diameter of the second loop section starting from a first end of the first loop section located opposite the second loop section, wherein the first loop section has a greater stiffness than the second loop section.
Claims
1. An ablation catheter for treatment of a patient's tissue by delivery of high-voltage pulses comprising: a catheter shaft and an ablation portion being arranged at a distal end of the catheter shaft with a plurality of electrodes accommodated along the ablation portion, wherein the ablation portion forms a spiral and comprises a first loop section and a neighboring second loop section, wherein an inner diameter of the first loop section increases towards an inner diameter of the second loop section starting from a first end of the first loop section located opposite the second loop section, wherein the first loop section has a greater stiffness than the second loop section.
2. The catheter of claim 1, wherein the ablation portion is connected to the catheter shaft by a transition joint.
3. The catheter of claim 1, wherein the ablation catheter further comprises a third loop section, which is a neighboring section to the second loop section, wherein an inner diameter of the third loop section increases along the third loop section starting with the end that is closest to the second loop section, wherein the third loop section has a greater stiffness than the second loop section.
4. The catheter of claim 1, wherein the respective stiffness of the first loop section, the second loop section and, if applicable, the third loop section is provided by the form and/or the material of a wire, of the respective loop section.
5. The catheter of claim 4, wherein a first diameter of the wire, of the first loop section is greater than a second diameter of the wire, of the second loop section, for example, the first diameter is between 350 μm and 700 μm and the second diameter is between 200 μm and 349 μm.
6. The catheter of claim 4, wherein the wire of the second loop section comprises at least one indentation and/or the wire of the first loop section and/or, if applicable, the wire of the third loop section comprises at least one elevation at its surface.
7. The catheter of claim 1, wherein a pitch and/or clearance is provided between the first loop section and the second loop section and, if applicable, between the second loop section and the third loop section.
8. The catheter of claim 7, wherein the pitch and/or clearance between the first loop section and the second loop section and, if applicable, the second loop section and the third loop section is between 2 mm and 8 mm, in particular between 4 mm and 6 mm.
9. The catheter of claim 1, wherein the first end of the first loop section is directly attached to the distal end of the catheter shaft or a second end of the second loop section or, if applicable, a second end of the third loop section is directly attached to the distal end of the catheter shaft, wherein the second end of the second loop section and, if applicable, the second end of the third loop section is located opposite the first loop section.
10. The catheter of claim 7, wherein the catheter shaft is generally located at or close to an axis of the spiral form of the ablation portion.
11. An ablation catheter for treatment of a patient's tissue by delivery of high-voltage pulses comprising: a catheter shaft and an ablation portion being arranged at a distal end of the catheter shaft with a plurality of electrodes accommodated spaced from one another along the ablation portion, wherein the plurality of electrodes comprises at least one first electrode of a first electrode type and at least one second electrode of a second electrode type, wherein a first surface area of the first electrode type is smaller than a second surface area of the second electrode type.
12. The ablation catheter of claim 11, wherein a sequence of accommodation of the electrodes along the ablation portion is such that one first electrode and one second electrode alternate.
13. The ablation catheter of claim 11, wherein the ablation portion forms a three-dimensional spiral, wherein a sequence of accommodation of the electrodes along the ablation portion is such that a plurality of second electrodes is accommodated along a spiral section having a greater inner diameter and that a plurality of first electrodes is accommodated along a spiral section having a smaller inner diameter.
14. A method to operate an ablation catheter according to claim 1, wherein in a first step the catheter shaft is moved distally within the patient's body until the second loop section or, if applicable, the third loop section is brought into contact with tissue at a pre-defined treatment area surrounding a recess, wherein in a second, consecutive step distal movement of the catheter shaft or of a wire connected to the distal end of the ablation portion forces the first loop section to advance into the recess and relatively to the second loop section and, if applicable, to the third loop section.
15. The method of claim 14, wherein in a third step provided after the second step the plurality of electrodes is energized with high-voltage charge-balanced pulsed electric fields which are delivered in a monopolar arrangement or in a bipolar arrangement or in a combination of a monopolar arrangement and a bipolar arrangement.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
[0040] The present invention will now be described in further detail with reference to the accompanying schematic drawing, wherein:
[0041] FIG. 1 depicts a distal end of a first embodiment of an ablation catheter in a perspective side view;
[0042] FIG. 2 illustrates a delivery path for an ablation catheter leading to a pulmonary vein ostium of a human heart;
[0043] FIGS. 3 and 4 show the distal end of the embodiment of FIG. 1 in a perspective front view and in a side view;
[0044] FIGS. 5 to 7 depict a distal end of a second embodiment of an ablation catheter in a side view, a front view and in a perspective front view;
[0045] FIGS. 8 to 11 depict a distal end of a third embodiment of an ablation catheter in side views and a front view;
[0046] FIG. 12 shows the distal end of the embodiment of FIG. 1 in a perspective side view with some marked dimensions;
[0047] FIG. 13 shows part of the electric control of the electrode leads for the embodiment of FIG. 1;
[0048] FIG. 14 shows electrical field vector distribution electronically steered to achieve a moat of conduction block;
[0049] FIGS. 15A-B illustrate exemplary waveforms that are charge balanced (Waveform in FIG. 15A is of exponential decay type. Waveform in FIG. 15B is of rectangular type);
[0050] FIGS. 16A-C illustrate the concept of QRS gating (FIG. 16A shows the QRS detector signal (top trace), the PFA trigger signal (middle trace) and the ECG (bottom trace) over several heart beats. FIG. 16B shows a detail into one heartbeat. The PFA trigger signal (middle trace) falls within the refractory period of the cardiac cycle. FIG. 16C shows the PFA pulse artifact, as recorded during a preclinical study);
[0051] FIG. 17 shows an actual histology slide identifying the moat of conduction block (or electrical isolation) around the right superior pulmonary vein (RSPV);
[0052] FIGS. 18A-C further exemplify a possible electrode distribution on a spiral distal section. FIG. 18A shows the catheter of this invention facing a PV. FIG. 18B shows the catheter of this invention deployed when pressed against PV wall. Note the clearance between spiral arms. FIG. 18C shows an alternative split-tip electrode construction;
[0053] FIG. 19 shows three schematic impedance curves measured over frequency between two electrodes;
[0054] FIGS. 20A-B show two examples of measured impedance over frequency;
[0055] FIGS. 21A-C depict the distal end of the second embodiment of FIG. 5 in a perspective side view in three different steps during positioning at an outer rim of a PV;
[0056] FIG. 22 shows the distal end of the embodiment of FIG. 5 in a different perspective side view;
[0057] FIG. 23 shows a possible movement of the distal end of the embodiment of FIG. 5 in a perspective side view;
[0058] FIG. 24 depicts a distal end of a fourth embodiment of an ablation catheter in a perspective side view;
[0059] FIG. 25 depicts a distal end of a fifth embodiment of an ablation catheter in a front view;
[0060] FIG. 26 depicts a distal end of a sixth embodiment of an ablation catheter in a front view; and
[0061] FIGS. 27A-C depict a distal end of a seventh embodiment in a perspective side view in three different steps during positioning at an outer rim of a PV.
DETAILED DESCRIPTION
[0062] FIGS. 1, 3, 4 and 12 schematically and exemplarily illustrate a distal portion of an ablation catheter 1 in accordance with a first embodiment. The ablation catheter may be used for PFA, when used with the PFA generator and accessories, and is indicated for use in cardiac electrophysiological mapping (stimulation and recording) and in high-voltage, pulsed-field cardiac ablation. Peak voltages are, for example, without limitation, +/−1 kV to 3 kV with a pulse width of up to 30 μs. Higher peak voltages (e.g. up to 10 kV) may be used provided the pulse duration is correspondingly shorter (e.g. 0.5 us). The catheter 1 has an elongated circular catheter shaft 10, which may connect with a handle comprising a steering mechanism at a proximal end (not illustrated). As a result, the catheter may control deflections of the depicted distal section carrying the ablation electrodes.
[0063] At the illustrated distal end of the catheter shaft 10 an ablation portion 12 is arranged, which comprises a plurality of loop sections. The concept of loop sections includes embodiments that use continuous loops or spirals configurations. In this case, the ablation portion has a first loop section 122 at the distal end of the ablation portion 12 (with inner diameter between D3 and D2, see FIG. 12) and an adjacent second loop section 121 (with inner diameter between D2 and D1). The catheter shaft may have an effective length of approximately 115 cm from the distal tip of the ablation portion 12. Each of the second loop section 121 and the neighboring first loop section 122 exhibits ablation electrodes 120 (altogether, for example, 14 electrodes), which are configured for delivering energy to tissue. Although two loops are illustrated in FIG. 1, more can be used. In one embodiment, at least a partial third loop section is used to provide sufficient overlap among resulting ablation zones. Said overlap would increase chances of achieving a conduction block moat without drops in lesion continuity, contiguity or transmurality. As an example, see catheter illustration in FIG. 14. The distal section comprises at least 45° of overlap of a 3.sup.rd loop section with the previous two sections. In particular, the ablation catheter 1 may be configured for delivering an electrical high voltage PFA signal to tissue via the ablation electrodes 120. For example, the ablation electrodes 120 may consist of or comprise gold and/or a platinum/iridium alloy. Alternatively, electrodes 120 from different loop sections may be positioned so that electrodes of same polarity are aligned. Either the staggering or the polarity-based approach ensures that electrodes of opposite polarities would not collide when the spiral catheter is compressed.
[0064] In the exemplary embodiment illustrated in FIG. 1, the ablation electrodes 120 of the second loop section 122 are arranged partly in a staggered manner with respect to the ablation electrodes 120 of the first loop section 121.
[0065] The loop sections 121, 122 may further exhibit a plurality of mapping electrodes, which are configured for receiving electrical signals from tissue.
[0066] Together, the loop sections 121, 122 form a three-dimensional spiral, which form a corkscrew-similar form. Alternatively, they may form a plunger-like configuration, as shown in the second embodiment, for example depicted FIGS. 5-7. It should be noted that respective diameters of the loop sections 121, 122 are such that the second, more proximal loop section 121 has a greater inner diameter D1 (for example 30 mm, see FIG. 12) than the first, more distal loop section 122 (inner diameter D2, for example 24 mm). At the furthest distal tip of the ablation portion 12 the inner diameter D3 is even lower (for example 18 mm). In general, the diameters of loop sections may be, for example, between 10 mm and 40 mm. More specifically, if used in the left atrium, the widest (second) loop section may have a diameter between 20-35 mm, preferably between 25-32 mm. The smallest diameter can be 12-22 mm, preferably 15-20 mm. In this embodiment, the second loop section 121 with the greatest diameter is directly attached to the distal end of the catheter shaft 10.
[0067] The loop sections 121, 122 may comprise a shape memory material, for example, in the form of an inner support structure, in particular a wire (not illustrated), for example a Nitinol wire as described above. In particular, the loop sections 121, 122 may have super-elastic properties.
[0068] The ablation portion 12 may be constrained into an essentially elongate shape for the purpose of delivery to a target region in the human body by means of a (fixed or steerable) delivery sheath 15, which may also be referred to as an introducer sheath. At the target position, upon exiting a distal end of the delivery sheath 15, the ablation portion 12 may then recoil to its original (biased) shape.
[0069] The length of each electrode 120 in longitudinal direction along the respective loop section 121, 122 is, for example, 4 mm. In general, the electrode length is in the range 1-10 mm, preferably 3-5 mm. The catheter shaft 10 size may be compatible with an 8.5 F ID sheath and may consist of radiopaque extrudable polymer and, if applicable, a polymer-reinforcing braid. In general, the size of the catheter shaft 10 may be compatible with a 7 F to 14 F ID sheath. The width between neighboring electrodes along the respective loop section may be chosen between 1 mm and 10 mm, preferably 3-6 mm, in order to provide a contiguous ablated area at the patient's tissue.
[0070] The first loop section 122 has a greater stiffness than the second loop section 121. Accordingly, the second loop section 121 comprises slits or small cuts/indentations at the surface of the support structure, in particular the wire, forming the loop. The indentations or slits can be short and perpendicular segments to the longitudinal axis of the loop of the wire.
[0071] Alternatively, the greater stiffness of the first loop section 122 may be provided by ribs at the surface of its support structure, wherein the second loop section does or does not comprise the indentations described above.
[0072] The above stiffness variation of the loop sections 121, 122 leads to a better adaption of the ablation portion 12 to the anatomy of the tissue to be treated and thereby to a better electrode contact.
[0073] FIG. 2 schematically and exemplarily illustrates a delivery path for an ablation catheter 1 leading to a pulmonary vein ostium (PVO) of a human heart. For orientation, the inferior vena cava (IVC), the right atrium (RA), the right ventricle (RV), the left atrium (LA), the left ventricle (LV), as well as pulmonary veins (PV), each with a PVO, are shown. The large black arrows indicate a delivery path passing through the IVC, the RA, transseptally through the septal wall (SW), and into the LA. Finally, using appropriate deflection means, catheter 1 is steered to PVO regions. There, the corkscrew type ablation catheter may be used for ablation in the area of the atrial end of the pulmonary vein close to PVO. The form of the ablation portion 12 is configured such that it fits to the dimensions of the targeted PVO. Alternatively, corkscrew-type catheters may be used to ablate at the SVC or at Appendages, such as the left or right atrial appendages (LAA or RAA).
[0074] The second embodiment of an ablation catheter 2 shown in FIGS. 5 to 7, 21A to C, 22, and 23 is adapted to the use for ablation in the atrial area of the left atrium LA surrounding the PVOs, or located between PVOs (e.g. posterior LA wall). Alternatively, catheter 2 may be well suited for ablations on ventricular (RV or LV) walls, or in the RA (e.g. free RA wall, Tricuspid Valve annulus, etc.). The ablation portion 22 comprises three loop sections 221, 222 and 223 with a plurality of ablation electrodes 220 (and, if applicable also with mapping electrodes). The form and positioning of the ablation electrodes 220 is similar to the electrodes 120 of the first embodiment. The ablation portion 22 is formed like a three-dimensional spiral having the form of a plunger (if no external mechanical force is exerted onto the ablation portion 22). The ablation portion comprises a first loop section 222 having the smallest inner diameter, a second loop section 221 having a diameter greater than the one of the first loop section 222 and a third loop section 223 having the greatest inner diameter. The first, second and third loop sections 222, 221, 223 are adjacent to each other as shown in the figures and a first end of the first loop section 222 is directly attached to the catheter shaft 20 at a transition joint 21 (see FIG. 21A). The first loop section 222 forms the proximal end of the ablation portion 22 and the third loop section 223 forms its distal end (if no external mechanical force is exerted onto the ablation portion).
[0075] As shown in FIG. 22 (not showing the electrodes for more clarity) the first diameter d1 of the wire of the first loop section 222, for example d1 is between 350 μm and 700 μm, is greater than the second diameter d2 of the wire of the second loop section 221. For example, the second diameter d2 is between 200 μm and 349 μm. Further, the diameter d3 of the wire of the third loop section 223 is greater than the diameter of the wire of the second loop section 221, for example d3 is between 350 μm and 700 μm. Accordingly, the first and the third loop sections 222, 223 have a greater stiffness than the second loop section 221. The different flexibility of the different loop sections provided by the different wire diameter.
[0076] The helical/spiral, expanded structure of the ablation portion 22 of this embodiment may be placed inside the chamber of the heart and e.g. over the opening of the PV as shown in FIG. 21A. By pushing the catheter shaft 20 in distal direction, the third loop section 223 contacts the outer rim 250 of the PV. Contact of the ablation electrodes 120 may be confirmed by indicators such as impedance and electric signals provided by ablation electrodes, if is applicable or a force sensor of the catheter. As shown in FIG. 21B, upon further distal movement of the catheter shaft 20, the ablation portion 22 is compressed, such that the first loop section 222, the second loop section 221 and the third loop section 223 form a flat spiral. Upon further distal movement of the catheter shaft 20 the catheter shaft further pushes the stiff first loop section 222 and advances into the PV together with the second loop section 221 until it reaches the position shown in FIG. 21C. The distal tip of the catheter shaft 20 that was initially (FIG. 21A) located proximal from the ablation portion 22 penetrates into the PV and in that moves past the third loop section 223 and the second loop section 221. The ablation portion 22 that was initial formed plunger-like (FIG. 21A) has, after insertion into the PV (FIG. 21C), a corkscrew-like form. In this way, caused by the reduced stiffness of the second loop section 221 an eversion of the helical/spiral loops is facilitated and sustained which leads to a better adaptation to the different individual anatomical shapes of the PVs for better tissue contact of the electrodes. Specifically, the outermost loop (third loop section 223) is sufficiently firm to sit on the PV antrum/ostium, while the middle loop (second loop section 221) is softer and more flexible to allow the helix to evert. The inner most loop (first loop section 222) forms a stiffer section that gives the everted helix stability.
[0077] As shown in FIG. 23 with regard to the second embodiment, while helical loops are in the everted state or in the inverted position, the catheter shaft 20 which is attached to the innermost loop (first loop section 222), may be steered to position the axis of the ablation portion 22 in alignment with the longitudinal axis of the PV. Since the steering or deflection point of the catheter shaft 20 in this everted state or inverted position is closer to or within the ablation portion 22 of the helical loops, finer or smaller movement of the first loop section 222 and the second loop section 221 can be made to achieve improved tissue contact for various anatomical topography.
[0078] There is a third embodiment shown in FIGS. 8 to 11 similar to the first embodiment. Without limitations though, elements of this embodiment (e.g. center wire 31, for spiral expandability or compression) may be used with other type of spiral catheter. Additional to the construction of the first embodiment the third embodiment of an ablation catheter 3 comprises a center wire 31, used to facilitate expandability or compression of the distal section. Center wire 31 is connected with the distal tip of the ablation portion 32. Ablation portion 32 carries ablation electrodes 320. Center wire 31 is running approximately along the longitudinal axis of the spiral formed by the ablation portion and its two loop sections 321, 322. Center wire 31 enters and runs inside catheter shaft 30. At the proximal end of the catheter, center wire 31 connects with actuating element associated with or integrated in the catheter handle. The center wire 31 may be manipulated such that a longitudinal length of the ablation portion 32 (i.e. its length along the longitudinal axis of the three-dimensional spiral of the ablation portion 32) and, accordingly the diameters of the loop sections 321, 322 may be changed and adapted to the therapeutic needs and the local situation. In the drawing of FIG. 8, the longitudinal length of the ablation portion is greatest compared with the drawings of FIGS. 9 and 10 because the center wire pushes the distal tip of the ablation portion 32 in a distal direction. Accordingly, the diameter of the loop sections 321, 322 is smallest. FIG. 10 shows the shortest longitudinal length of the ablation portion 32 of the ablation catheter 3. This is achieved by pulling the center wire 31. The ablation catheter 3 shown in FIG. 9 has a nominal longitudinal length of the ablation portion 32, which is between those of FIGS. 8 and 10. Hence, the diameter of the loop sections 321, 322 is greatest in FIG. 10 and smallest in FIG. 8.
[0079] FIG. 24 shows an ablation catheter 4 according to a fourth embodiment that comprises a first loop section 422, a second loop section 421 and a third loop section 423. The ablation catheter 4 is similar to the ablation catheter 2 of the second embodiment (also with regard to the electrodes which are not shown in FIG. 24) but compared to the second embodiment the pitch of the loop sections 422, 421, 423 is so small, that a flat spiral is formed. As one can derive from FIG. 24, the first diameter of the wire of the first loop section 422 is greater than the second diameter of the wire of the second loop section 421. Additionally, the third diameter of the wire of the third loop section 423 is greater than the second diameter of the wire of the second loop section 421. Accordingly, the ablation portion 42 of the ablation catheter 4 may be everted similar to the second embodiment so that steps similar to FIGS. 21B and 21C may be realized.
[0080] A fifth and a seventh embodiment of an ablation catheter 5, 7 shown in FIGS. 25 and 27A to C are similar to the second embodiment described above except the electrode structure. Accordingly, the reference numbers with similar last two numbers correspond to the second embodiment having the same structure and function. The fifth and seventh embodiments also comprise the same wire diameter variation as the second embodiment. The ablation portion 52, 72 comprises a plurality of ablation electrodes 520, 720 having a greater surface area than a plurality of mapping electrodes 530, 730 located at the first loop section 522, 722. For example, the mapping electrodes 530, 730 have a length of, for example, 0.5 to 1.0 mm in longitudinal direction along the ablation portion 52, 72 whereas the ablation electrodes 520, 720 have a length of, for example, 3 to 5 mm in longitudinal direction along the ablation portion 52, 72. The mapping electrodes 730 of the seventh embodiment shown in FIG. 27A to C are grouped so that every two electrodes are positioned closer to each other. In contrast, the mapping electrodes 530 are equidistantly spaced to each other. When everting the spiral structure of the ablation portion 52, 72 as shown in FIG. 27C, the mapping electrodes 530, 730 are located at the distal end of the catheter so that above explained mapping is provided with some distance from the ablation area formed by the ablation electrodes 520, 720. This enables mapping simultaneously with ablation.
[0081] In a sixth embodiment which is also similar to the second embodiment, the plurality of mapping electrodes 630 are arranged such with the plurality of ablation electrodes 620 along the ablation portion 62 that one mapping electrode 630 alternates with one ablation electrode 620. In this embodiment, mapping is provided with ablation in subsequent steps.
[0082] Due to their small size the mapping electrodes 530, 630, 703 may be used for localized, high density mapping.
[0083] Reliable full ablation along a whole circumference is achieved with the first to seventh embodiment at their respective position within the heart or the vein to which the form is adapted.
[0084] In order to spare adjacent tissue and shorten ablation time, the pitch of neighboring loop sections is chosen between the ionization threshold and the therapeutic threshold when they are correctly positioned at the treatment area. Referring to the first embodiment shown in FIG. 12, the first pitch, or clearance, s1 of the second loop section 121 and the first loop section 122 is approximately 5 mm and the second pitch, or clearance, s2 of the first loop section 122 and the furthest distal end of the ablation portion 12 is approximately 5 mm, as well. In general, the pitch, or clearance, should be between the ionization (2 mm) and therapeutic thresholds (up to 8 mm). It is important that the angular offset between most distal and most proximal electrodes on any of the above described catheters exceeds 2*360°, preferably it is 2*360°+45° (i.e. two full loops plus ⅛ of a third loop).
[0085] The ablation procedure using one of the ablation catheters 1 to 7 may start after the ablation portion 12, 22, 32, 42, 52, 62, 72 is in the correct position relative to the targeted tissue, for example at a PVO. The ablation electrodes 120, 220, 320, 420, 520, 620 will provide pulsed electric RF field in a monopolar or bipolar arrangement. Peak voltages are, for example, without limitation, +/−1 kV to 3 kV with a pulse width of up to 30 μs. Higher peak voltages (e.g. up to 10 kV) may be used provided the pulse duration is correspondingly shorter (e.g. 0.5 us). The pulse width may be 12 μs (between 0.5-30 μs) forming a pulse train comprising up to 500 pulses/train. Any of the waveforms illustrated in FIGS. 15A-B may be used.
[0086] Without limitations, as an example, waveform in FIG. 15A shows biphasic exponentially decaying voltage pulses suitable for PFA treatment. Over the entire waveform complex, the exponential decays achieve a charge-balanced goal, needed to minimize chances of bubbling, arcing or undesired tissue stimulation. Such waveforms may be achieved by using high-voltage output stages which are AC-coupled to the ablation electrodes 120, 220, 320, 420, 520, 620, 720. The two biphasic pulses shown in FIG. 15A form a pulse train, which could be repeated N-times. The biphasic pulses consist of a positive section PP and a negative section PN. As shown in FIG. 15A a positive biphasic pulse is followed by an inverse negative biphasic pulse. The interphase delay I.sub.1 is the time between the end of the negative section PN of the first biphasic pulse and the start of the positive section of the following pulse. As defined above the pulse width P corresponds to the length of the positive/negative section PP/PN, if biphasic pulses are used. The next pulse train starts after the interpulse delay I.sub.2.
[0087] Similarly, FIG. 15B shows an example of suitable PFA waveforms which have rectangular shapes. The rectangular pulses as shown in FIG. 15B are characterized by the voltage peak V and the pulse width P. A positive rectangular pulse is followed by a negative rectangular pulse after the interphase delay I.sub.1. The two pulses shown in FIG. 15B form a pulse train, which is repeated N-times. The next pulse train starts after the interpulse delay I.sub.2. These waveforms are also charge balanced. Such charge-balanced rectangular waveforms may be achieved by using DC-coupled high-voltage output stages with reasonably accurate control of the positive and negative phase amplitude and duration. As a result, the net charge (current amplitude*pulse width) can be controlled to achieve net balancing.
[0088] FIGS. 16A-C show QRS-gated output waveforms. A typical lead-I ECG waveform 1601a is shown in FIG. 16A. The output of the QRS detector is illustrated as signal 1602a. The trigger of the PFA waveform is shown as signal 1603a. FIG. 16B provides a zoomed-in view of FIG. 16A. The ECG waveform 1601b is represented over one cardiac cycle. Its R-wave 1604 is detected by the QRS detector output 1602b. After a programmed delay 1605, the PFA waveform trigger 1603b is turned on. In this embodiment, delay 1605 is shown to be about 70 ms. Delay 1605 may be between 20-150 ms, depending on the heart rate. It is important to make sure PFA pulses are applied within the refractory period of the heart. As FIG. 16B shows, in this particular example the train of pulse ends before the beginning of T wave 1606. FIG. 16C shows an example of PFA pulses artifacts, as recorded with a standard cardiac recording system. R wave 1604c is seen being followed by artifacts 1607 caused by delivery of PFA pulses. Artifacts 1607 safely end before the beginning of T waves 1606c. The process described above delivers one train of pulses within one cardiac cycle. In the above example, 10 pulses/train were delivered using waveform 1501 from FIG. 15A. Persons of skill in the art may modify the above approach by using other known parameters without departing from the essence of this invention. For example up to 500 pulse trains may be provided. However, although not required, it is preferable to select a number of trains so that to keep the PFA application time to greater than 1 s (to allow of cell membrane poration) but less than 2 min (to avoid long procedures). The interphase delay may be 1-100 μs. The interpulse delay may be 0.1 ms or 100 ms.
[0089] The electric field generation (in particular voltage, current and impedance) is monitored by an electronic control unit (ECU) 70 which is connected to the leads 61 of the electrodes 120, 220, 320, 420, 520, 620, 720 and produced by a waveform generator 50 (see FIG. 13). FIG. 14 also shows connectivity that can be used to generate monopolar or bipolar electric fields. ECUs in FIGS. 13 and 14 may control application of PFA fields with a goal of achieving wide coverage of the tissue space in between catheter loops or spirals. FIG. 14 illustrates a catheter 1401 (such was #1, #2 or #3 from FIGS. 1-10) with its electrodes driven by ECU 1403. ECU 1403 can be controlled to deliver field vectors 1402 that cover the tissue zone in between catheter 1401 spiral arms/loops. By doing so, a moat of conduction block/electrical isolation is more likely to be achieved.
[0090] In the bipolar arrangement neighboring (adjacent) electrodes 120, 220, 320, 420, 520, 620, 720 may be paired along the loop sections, for example 121, 122, 212, 222, 321, 322 or across two neighboring loop sections, for example 121 and 122; 221 and 222; 321 and 322. Further, the electrodes 120, 220, 320, 420, 520, 620, 720 may be used in monopolar arrangement. In this case, a ground pad 1404 may be provided at the surface of the patient's body. Alternatively, reference electrodes associated with the catheter shaft may be used.
[0091] In order to switch between different bipolar arrangements or between monopolar and bipolar arrangement, the ablation catheter 1, 2, 3, 4, 5, 6, 7 may comprise a switch unit 60 connected to and controlled by the ECU 70. The switch unit 60 provides the respective phase of the pulsed electric field provided by the waveform generator 50 to the predefined electrode lead 61 and thereby to the predefined electrode 120, 220, 320, 420, 520, 620, 720, wherein each electrode lead 61 is electrically connected to one particular electrode 120, 220, 320, 420, 520, 620, 720 at the ablation portion 12, 22, 32, 42, 52, 62, 72. The switch unit 60 comprises a switch matrix and may realize any configuration of phase distribution, for example, such that two neighboring electrodes along the loop sections or across the loop sections are paired to achieve the aforementioned uniform moat of conduction block. Any other configuration is possible. The switching signal and configuration information is provided by the ECU 70. ECU 70 further may provide data processing of electrical or biopotential data or impedance data acquired by mapping electrodes of ablation catheters 1 to 7. As indicated above mapping electrodes 530, 630, 730 located in the ablation portions 52, 62, 72 may comprise mapping electrodes for determining the electrical potential of the surrounding tissue in order to observe the is ablation progress at pre-defined time points during ablation procedure. Alternatively, the ablation electrodes 120, 220, 320, 420 may be switched into the mapping mode and back into the ablation mode. Further, the impedance between neighboring electrodes or across two different, neighboring loop segments may be determined prior to delivery of PFA energy. Thereby impedance (monopolar or bipolar) is monitored whether the neighboring loop segments and hence the electrodes of these segments are located in a sufficient distance to the other loop segment or electrode, respectively. By monitoring impedance, ECU 70 or 1403 may alert the user when any two electrodes are too close, with respective inter electrode distance falling below the ionization threshold. Conversely, users may be alerted when impedance measurements indicate that the inter electrode distance exceeds the therapeutic threshold.
[0092] As indicated above, the catheter shaft 10, 20, 30, 40, 50, 60, 70 may comprise two lumens separated by a material, e.g. Kapton®, with a dielectric strength greater than a dielectric threshold for high-voltage PFA pulses. The first lumen may retain, for example, 7 electrode leads 61 providing the first polarity and the second lumen may retain, for example, 7 electrode leads 61 providing a second polarity thereby reducing the overall diameter of the catheter shaft.
[0093] The above explained embodiments of ablation catheters realize IRE in order to prevent spread of electrical signals (i.e. achieve conduction block) that gives rise to the cardiac arrhythmia along a contiguous area with improved safety, as it is believed to spare adjacent tissues (e.g. nerves, vessels, esophagus), and with shorter ablation time. FIG. 17 illustrates such moat of conduction block, or electrical isolation. The right superior pulmonary vein 1701 is seen at the center of the picture. After application of PFA pulses according to this invention (totaling cumulative PFA application time of about 90 s/PV), a continuous, contiguous and transmural lesion was achieved. The lesion perimeter 1402 is illustrated. The moat of conduction block, or electrical isolation, 1403 completely covers the cardiac tissue zone between RSPV 1401 and the lesion border 1402. Electroanatomic mapping confirmed lasting chronic isolation of pulmonary veins.
[0094] FIG. 18A shows the catheter of this invention facing a pulmonary vein atrium. FIG. 18B shows the catheter of this invention deployed when pressed against pulmonary vein wall. As indicated by line c1 and c2 the angular separation between the most distal electrode 1802 and the most proximal electrode 1801 exceeds 2*360°, or 720°. FIG. 18C shows an alternative split-tip electrode construction with an inner electrode facing the blood and an outer electrode facing the tissue.
[0095] FIG. 19 shows three schematic impedance curves measured over frequency between two electrodes. The impedance could be measured starting with a low frequency f.sub.low of 10 kHz up to a frequency f.sub.high of 500 kHz. A pronounced impedance curve as the topmost curve ranging from Z.sub.1 to Z.sub.4 indicates a good tissue contact between the two electrodes. A flat lowermost impedance curve in the lower range of Z.sub.3 to Z.sub.5 indicates contact between the two electrodes. The flat impedance curve in the middle ranging from Z.sub.2 to Z.sub.4 indicates bad tissue contact between the two electrodes. For example, without limitation, following thresholds may be used: [0096] 1. Good tissue contact—at f.sub.LOW (e.g. 10 kHz) Z.sub.1 is in the range 100-500 ohm, depending on electrode size and tissue properties. At f.sub.HIGH (e.g. 500 kHz) Z.sub.4 is at least 20% lower than Z.sub.1 (S-curve). [0097] 2. Poor contact—at f.sub.LOW (e.g. 10 kHz) Z.sub.2 is in the range of 80-400 ohm, depending on electrode size and blood properties. At f.sub.HIGH (e.g. 500 kHz) Z.sub.4 is at most 20% lower than Z.sub.2, typically only 10% or less lower (flat curve). As shown in FIG. 20A, under poor electrical contact conditions, the bipolar impedance decreases from about 113 ohm at 10 kHz to about 110 ohm at 500 kHz. The phase varies only slightly, increasing from about −4° to 2°. [0098] 3. Electrodes in contact—at f.sub.LOW (e.g. 10 kHz) Z.sub.3 is in the range 0-300 ohm, depending on the amount of contact, electrode size, blood properties. At f.sub.HIGH (e.g. 500 kHz) Z.sub.5 is at most 20% lower than Z.sub.3, typically only 10% or less lower (flat curve). As shown in FIG. 20B, when electrodes collide and make good electrical contact, Z.sub.5 is low, between 4-9 ohm, while phase increases with frequency. At 500 kHz, the phase is approximately 66°, indicating a mostly inductive electrical characteristic given by the electrode wires.
[0099] It will be apparent to those skilled in the art that numerous modifications and variations of the described examples and embodiments are possible in light of the above teachings of the disclosure. The disclosed examples and embodiments are presented for purposes of illustration only. Other alternate embodiments may include some or all of the features disclosed herein. Therefore, it is the intent to cover all such modifications and alternate embodiments as may come within the true scope of this invention, which is to be given the full breadth thereof. Additionally, the disclosure of a range of values is a disclosure of every numerical value within that range, including the end points.
