JPWO2019133608A5

JPWO2019133608A5 -

Info

Publication number: JPWO2019133608A5
Application number: JP2020535579A
Authority: JP
Publication date: 2023-04-19

Description

いくつかの実施形態では、不整脈を治療するために、通路は心臓内に設けられ、機能上連続的な治療区域は肺静脈と左心房との間に電気的切断を含む。任意選択的に、通路は肺静脈を含む。いくつかの実施形態では、機能上連続的な治療区域は、貫壁性病変を含む。他の実施形態では、通路は肺内に気道を含み、機能上連続的な治療区域は、気道の軟骨層を維持しながら、細胞型の空孔を作り出す。いくつかの実施形態では、細胞型は、上皮細胞、杯状細胞及び／又は粘膜下腺細胞を含む。いくつかの実施形態では、機能上連続的な治療区域は、最大２．５ｃｍまで且つこれを超えない深度を有する。 In some embodiments, a passageway is provided in the heart to treat an arrhythmia and the functionally continuous treatment segment includes an electrical disconnection between the pulmonary veins and the left atrium. Optionally, the passageway includes pulmonary veins. In some embodiments, the functionally continuous treatment area comprises a transmural lesion. In other embodiments, the passageway comprises an airway within the lung, and the functionally continuous treatment zone creates a cell-type void while maintaining the cartilaginous lining of the airway. In some embodiments, the cell types comprise epithelial cells, goblet cells and/or submucosal gland cells. In some embodiments, the functionally continuous treatment zone has a depth of up to and not exceeding 2.5 cm.

いくつかの実施形態では、通路は心臓内に設けられ、カテーテルの遠位端部は心臓内に位置決めされるように構成されるとともに、少なくとも１つのエネルギー送達アルゴリズムは、不整脈を治療するために機能上連続的な治療区域に肺静脈と左心房との間に電気的切断を含むようにさせる信号パラメータを含む。任意選択的に、通路は肺静脈を含み、カテーテルの遠位端部は肺静脈内に位置決めされるように構成されている。いくつかの実施形態では、信号パラメータは機能上連続的な治療区域に貫壁性病変を含むようにさせる。 In some embodiments, the passageway is provided within the heart, the distal end of the catheter is configured to be positioned within the heart, and the at least one energy delivery algorithm functions to treat an arrhythmia. Contains signal parameters that cause the continuous treatment segment to include electrical disconnection between the pulmonary veins and the left atrium. Optionally, the passageway includes a pulmonary vein and the distal end of the catheter is configured to be positioned within the pulmonary vein. In some embodiments, the signal parameters cause the functionally continuous treatment area to include transmural lesions.

ＰＶ－ＬＡ導通再開の推定される理由は、アブレーションライン内のギャップ及び／又は経壁病変生成の失敗である。ラインのギャップは、ＰＶからＬＡへの電気的活動の再開を可能にし、ＰＶトリガに心房細動を再度開始させるとともに、他のマイクロリエントラント心房性不整脈のトリガとしてもまた機能する場合がある。同様に、可逆的な心房損傷は、不完全な病変形成に起因する場合があり、一時的な電気的結合解除を生じるが、細胞死は生じない。線状病変全体にわたる永続的な導通遮断は、細胞死を伴う貫壁性病変を必要とし、且つ／又は使用する。前述したように、本開示の専用のカテーテル設計、別個のエネルギー送達アルゴリズム、及び使用方法は、周方向のアブレーションの規則性の向上を提供する。これにより、アブレーションライン内の導通ギャップが減少する。加えて、本開示の専用のカテーテル設計、別個のエネルギー送達アルゴリズム、及び使用方法は、貫壁性病変を形成する能力を高めることが可能である。このような改良は、心房細動を治療する際に有益な場合があるとともに、肺通路、胃腸の通路、並びに、身体内の他の自然通路及び人工通路を含む、多種多様な他の症状及び／又は他の体腔を治療する際に有用な場合がある。 Probable reasons for PV-LA continuity resumption are gaps in the ablation line and/or failure to create a transmural lesion. The line gap allows resumption of electrical activity from the PV to the LA, causing the PV trigger to re-initiate atrial fibrillation and may also serve as a trigger for other micro-reentrant atrial arrhythmias. Similarly, reversible atrial injury may result from incomplete lesion formation, resulting in transient electrical decoupling but not cell death. A permanent conduction block across a linear lesion requires and/or uses a transmural lesion with cell death. As previously described, the specialized catheter design, separate energy delivery algorithms, and methods of use of the present disclosure provide improved regularity of circumferential ablation. This reduces the conduction gaps in the ablation line. Additionally, the specialized catheter design, discrete energy delivery algorithms, and methods of use of the present disclosure can enhance the ability to form transmural lesions. Such improvements may be beneficial in treating atrial fibrillation, as well as in a wide variety of other conditions and conditions, including pulmonary passageways, gastrointestinal passageways, and other natural and artificial passageways within the body. /or may be useful in treating other body cavities.

図８に示されているように、エネルギーの限局的送達を多種多様なやり方で利用して、組織への効果を向上及び／又は最大化することができる。特に、電極（例えば２１２ａ、２１２ｂ、２１２ｃ、２１２ｄ）へのエネルギー送達の正確なタイミング及び順番付けを利用して、以下でさらに説明するように、エネルギーを受け取る組織内の細胞死を確実にすることができる。これは、心房細動の治療に特に有用な場合がある。前述したように、線状病変全体にわたる永続的な導通遮断は、一時的な可逆的効果ではなく、細胞死を伴う貫壁性病変を使用し、且つ／又は必要とする。いくつかの実施形態では、ＰＥＦ波形は、ナノ秒からマイクロ秒のパルス持続時間を反映する周波数を有する双極性の相殺を用いて、麻痺者の有無にかかわらず、細胞及び細胞小器官膜の両方を不安定化させる能力を保持しながら、全身性の筋収縮の程度を容認可能な低レベルまで軽減するものである。これは、ナノ秒のパルス電界（ｎｓＰＥＦ）又は従来のミリ秒の不可逆的電気穿孔（ＩＲＥ）法のいずれかを用いて到達したものを超える、一意的に治療結果を強化する素因となる細胞に及ぼす色々な形態の効果を誘発する。したがって、送達されるエネルギーは、標的組織で十分に大きく、且つ効果的な治療ゾーンを誘発することができるが、これは、ｎｓＰＥＦにとっての課題であり、一方、有利な安全性及び筋収縮プロファイルを維持することは、従来のミリ秒のＩＲＥにとっての、特に、外部の分散パッドを使用する単極パルス送達構成にとっての課題である。 As shown in FIG. 8, localized delivery of energy can be utilized in a wide variety of ways to enhance and/or maximize tissue effects. In particular, utilizing precise timing and sequencing of energy delivery to the electrodes (e.g., 212a, 212b, 212c, 212d) to ensure cell death within the tissue receiving the energy, as further described below. can be done. This may be particularly useful in treating atrial fibrillation. As noted above, permanent conduction block across linear lesions uses and/or requires transmural lesions with cell death rather than transient reversible effects. In some embodiments, PEF waveforms are applied to both cell and organelle membranes with and without paralysis using bipolar cancellation with frequencies reflecting pulse durations from nanoseconds to microseconds. It reduces the degree of generalized muscle contraction to an acceptably low level while retaining the ability to destabilize the . This predisposes cells to uniquely enhance therapeutic outcomes beyond those reached using either nanosecond pulsed electric fields (nsPEF) or conventional millisecond irreversible electroporation (IRE) methods. trigger various forms of effects. Thus, the delivered energy can induce a sufficiently large and effective treatment zone at the target tissue, which is a challenge for nsPEF, while providing favorable safety and muscle contraction profiles. Sustainability is a challenge for conventional millisecond IREs, especially for unipolar pulse delivery configurations that use external dispersive pads.

Claims

A method performed by a system for treating a passageway in the body having an inner perimeter, comprising:
positioning the electrode within the passage such that the electrode spans a portion of the inner perimeter of the passage;
creating a first treatment zone along a first portion of the inner perimeter of the passageway by supplying pulsed electric field energy to the electrode;
repositioning the electrode within the passageway one or more times such that the electrode spans an additional portion of the inner perimeter each time the electrode is repositioned;
creating additional treatment zones along each additional portion of the inner circumference of the passageway by supplying pulsed electric field energy to the repositioned electrodes each time the electrodes are repositioned;
including
The method of claim 1, wherein the first portion and each additional portion extend along the inner circumferential surface to create a treatment zone across the inner circumferential surface that is functionally continuous in terms of therapeutic efficacy .

A system for treating a passageway in the body, comprising:
a catheter comprising a first electrode near a distal end of said catheter and at least one additional electrode near a distal end of said catheter, said first electrode and the at least one additional electrode is positioned within the passageway such that the distal end of the catheter is aligned to transmit pulsed electric field energy to a single inner circumferential surface of the passageway. a catheter configured to;
a generator in electrical communication with the first electrode and the at least one additional electrode,
a) supplying an electrical signal of said pulsed electric field energy to said first electrode to prioritize energy delivery through said first electrode to create a first treatment zone;
b) directing said electrical signal of said pulsed electric field energy to each of said at least one additional electrode so as to prioritize energy delivery through each of said at least one additional electrode when the electrical signal is applied; switching to individual delivery to create additional treatment areas corresponding to each of the at least one additional electrode;
the generator including at least one energy delivery algorithm;
including
The first treatment zone and the additional treatment zone are arranged inside the single interior of the passageway to create a treatment zone that spans the single inner perimeter and is functionally continuous in terms of therapeutic efficacy. A system extending along the perimeter.

the passageway is provided within the heart, the distal end of the catheter is configured to be positioned within the heart;
The at least one energy delivery algorithm causes the treatment area that is functionally continuous in terms of therapeutic efficacy to include electrical disconnection between the pulmonary veins and the left atrium to treat an arrhythmia. 3. The system of claim 2, including parameters.

4. The system of claim 3, wherein the passageway includes the pulmonary vein and the distal end of the catheter is configured to be positioned within the pulmonary vein.

5. The system of claim 4, wherein the signal parameter causes the treatment area that is functionally continuous in terms of therapeutic efficacy to include transmural lesions.

the passageway includes an airway of the lung , the distal end of the catheter being configured to be positioned within the airway;
The at least one energy delivery algorithm includes signal parameters that cause the treatment area to be functionally continuous in terms of therapeutic efficacy to contain cellular voids while maintaining the cartilage layer of the airway . 3. The system of claim 2.

7. The system of claim 6, wherein said cell types comprise epithelial cells, goblet cells and/or submucosal gland cells.

7. The system of claim 6, wherein the treatment zone that is functionally continuous in terms of therapeutic effect has a depth of up to and not exceeding 2.5 cm.

The system of any one of claims 2-8, wherein the pulsed electric field energy is biphasic.

The at least one energy delivery algorithm delivers pulsed electric field energy to at least one of the plurality of electrodes for 10,000 μs or less to perform the first treatment area and/or the at least one additional treatment. A system according to any one of claims 2 to 9, producing each of the zones.

The at least one energy delivery algorithm delivers pulsed electric field energy to at least one of the plurality of electrodes for 500 μs or less to effect the first treatment area and/or the at least one additional treatment area. 11. The system of claim 10, producing each.

The at least one energy delivery algorithm delivers pulsed electric field energy to at least one of the plurality of electrodes for 5 μs to 50 μs to the first treatment area and/or the at least one additional treatment area. 12. The system of claim 11, which produces each of

A system according to any one of claims 2 to 12, wherein said pulsed electric field energy is composed of 1000 or fewer packets.

14. The system of claim 13, wherein said pulsed electric field energy consists of 40-500 packets.

14. The system of claim 13, wherein the pulsed electric field energy is composed of 10 or fewer packets.

The system of any one of claims 2-15, wherein the pulsed electric field energy is delivered in a monopolar configuration.

The system of any one of claims 2-16, wherein said at least one additional electrode comprises 2-7 additional electrodes.

18. Any one of claims 2-17, wherein the at least one energy delivery algorithm supplies the electrical signal of the pulsed electric field energy to each of the first electrode and at least one additional electrode in succession. The system described in .

The system of any one of claims 2-18, wherein the first treatment zone and the at least one additional treatment zone overlap.

The system of any one of claims 2-19, wherein the at least one energy delivery algorithm is configured to provide the electrical signal of the pulsed electric field energy to the first electrode in multiple stages. .

The at least one energy delivery algorithm is configured to provide the electrical signal of the pulsed electric field energy to the at least one additional electrode in a plurality of different stages, the plurality of stages and the plurality of different stages simultaneously. 21. The system of claim 20, which does not occur.

22. The system of claim 21, wherein said plurality of stages and said plurality of different stages form a repeating pattern.

said at least one energy delivery algorithm supplying maintenance pulse electric field energy to said first electrode and/or said at least one additional electrode between stages;
22. The system of claim 21, wherein said maintenance pulse electric field energy has a lower voltage than said pulse electric field energy.

24. The system of claim 23, wherein said maintenance pulse electric field energy has a voltage less than half the voltage of said pulse electric field energy.

The system of any one of claims 2-24, wherein the at least first electrode and the at least one additional electrode are mounted on or embedded within an expandable member.

said at least first electrode and said at least one additional electrode comprising a plurality of wires or ribbons forming an electrode delivery body having an expandable basket shape;
A system according to any one of claims 2 to 24, wherein said basket-shaped part is insulated.

A system for treating a passageway in the body, comprising:
a catheter comprising at least one electrode located near a distal end of said catheter, said at least one electrode being capable of transmitting pulsed electric field energy to an inner surface of said passage; a catheter configured such that the distal end of the catheter is positioned within the passageway;
at least one generator in electrical communication with the at least one electrode for providing an electrical signal to the at least one electrode such that pulsed electric field energy is delivered to cells on the inner surface of the passageway; the generator including one energy delivery algorithm;
including
the electrical signal includes a plurality of packets;
each packet includes a plurality of biphasic cycles, and
Each packet is separated in time by 0.0001 to 10 seconds, system.

28. The system of claim 27, wherein said plurality of packets generate said pulsed electric field energy for 10,000 [mu]s or less.

29. The system of claim 28, wherein said plurality of packets produce said pulsed electric field energy for 500[mu]s or less.

30. The system of claim 29, wherein said plurality of packets produce said pulsed electric field energy for 5 μs to 50 μs or less.

The system of any one of claims 27-30, wherein said pulsed electric field energy is composed of 1000 or fewer packets.

32. The system of claim 31, wherein said pulsed electric field energy consists of 40-500 packets.

32. The system of claim 31, wherein the plurality of packets includes ten packets or less.

34. The system of any one of claims 27-33, wherein the pulsed electric field energy is delivered in a monopolar configuration.

Claims 27-34, wherein said at least one electrode comprises at least a first electrode and at least one additional electrode arranged to deliver said pulsed electric field energy circumferentially to said inner surface of said passageway. A system according to any one of Claims 1 to 3.

36. The method of claim 35, wherein the at least one energy delivery algorithm delivers the plurality of packets to the first electrode prior to delivering another plurality of packets to each of the at least one additional electrode. System as described.

37. The at least one energy delivery algorithm supplies another plurality of packets to each of the at least one additional electrode before finishing delivering the plurality of packets to the first electrode. The system described in .

said at least one energy delivery algorithm delivering maintenance pulse electric field energy to said first electrode and/or said at least one additional electrode between packets;
36. The system of claim 35, wherein said maintenance pulse electric field energy has a lower voltage than said pulse electric field energy.

39. The system of claim 38, wherein said maintenance pulse electric field energy has a voltage less than half the voltage of said pulse electric field energy.

further comprising a cardiac monitor configured to acquire a cardiac signal of the patient;
39. The system of Claim 38, wherein the generator provides the maintenance pulse electric field energy synchronously with the cardiac signal.

41. The system of any one of claims 35-40, wherein the at least first electrode and the at least one additional electrode are mounted on or embedded within an expandable member.

said at least first electrode and said at least one additional electrode comprising a plurality of wires or ribbons forming an electrode delivery body having an expandable basket shape;
The system of any one of claims 35-40, wherein said basket-shaped portion is insulated.

43. Any one of claims 27-42, wherein the pulsed electric field energy is delivered to the cells on the inner surface of the passageway to disrupt cellular homeostasis at depths up to and not exceeding 2.5 cm. A system as described in .

further comprising a cardiac monitor configured to acquire a cardiac signal of the patient ;
The system of any one of claims 27-43, wherein the generator provides the electrical signal synchronously with the cardiac signal.

A method performed by a system for treating a passageway in the body having an inner perimeter, comprising:
positioning a plurality of electrodes within the passage such that the plurality of electrodes span at least a portion of the inner perimeter of the passage;
creating a first treatment zone along a first portion of the inner circumferential surface of the passageway by supplying pulsed electric field energy to at least one of the plurality of electrodes, the plurality of electrodes comprising: prioritizing energy delivery to the first treatment area through the at least one of;
creating at least one additional treatment zone along at least one additional portion of the inner circumferential surface of the passageway by supplying pulsed electric field energy to at least one of the plurality of electrodes; prioritizing energy delivery to the at least one additional treatment area through the at least one of the plurality of electrodes;
including
The method, wherein the first portion and the at least one additional portion extend along the inner circumferential surface to create a balanced treatment zone for energy transferred to the inner circumferential surface .

A system for treating a passageway in the body, comprising:
a catheter comprising a first electrode near a distal end of said catheter and at least one additional electrode near a distal end of said catheter, said first electrode and the at least one additional electrode is positioned within the passageway such that the distal end of the catheter is aligned to transmit pulsed electric field energy to a single inner circumferential surface of the passageway. a catheter configured to;
a generator in electrical communication with the first electrode and the at least one additional electrode,
a) supplying an electrical signal of said pulsed electric field energy to said first electrode to prioritize energy delivery through said first electrode to create a first treatment zone;
b) applying an electrical signal of said pulsed electric field energy to each of said at least one additional electrode so as to prioritize energy delivery through each of said at least one additional electrode when said electrical signal is provided; to individually supply the at least one additional electrode to create additional treatment zones corresponding to each of the at least one additional electrode;
the generator including at least one energy delivery algorithm;
including
The first treatment zone and the additional treatment zone extend along the single inner perimeter of the passageway to create a balanced treatment zone for energy transferred to the inner perimeter. do, the system.