CN114096205A - 用于产生房间分流管的系统和方法 - Google Patents
用于产生房间分流管的系统和方法 Download PDFInfo
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- CN114096205A CN114096205A CN202080049190.XA CN202080049190A CN114096205A CN 114096205 A CN114096205 A CN 114096205A CN 202080049190 A CN202080049190 A CN 202080049190A CN 114096205 A CN114096205 A CN 114096205A
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- Surgical Instruments (AREA)
Abstract
本发明提供了一种用于精确控制穿过房间隔的血流的装置。该装置包括护套,该护套具有设置在第一心房内的第一组开口,而第二组开口设置在第二心房内。致动器可被致动以在护套内移动内套管,从而修改第二组开口的面积,以允许血液响应于穿过房间隔的压力梯度,以与护套的第二组开口的面积相对应的血流速率经由第一和第二开口而在第一和第二心房之间流动。此外,可响应于在开口的每个增量面积处穿过房间隔的血液分流来监测患者的血流动力学,以便为患者选择特定尺寸的可植入式房间分流管。
Description
相关申请的交叉引用
本申请要求2019年5月20日提交的美国临时专利申请第62/850,511号的优先权的权益,其全部内容通过引用并入本文。
技术领域
本申请总体上涉及用于产生房间分流管的系统和方法,以将血液从一个心腔重新分配到另一个心腔,从而解决诸如心力衰竭(“HF”)、心肌梗死(“MI”)和肺动脉高压(“PAH”)等病理学问题。
背景技术
心力衰竭是心输出量不足以满足身体需要或只能在较高的充盈压下才能满足身体需要的生理状态。HF有许多潜在原因,包括心肌梗死、冠状动脉疾病、瓣膜病、高血压和心肌炎。慢性心力衰竭与神经激素激活和自主神经控制的改变有关。尽管这些代偿性神经激素机制在正常生理条件下为心脏提供了有价值的支持,但它们在HF的发展和后续进展中也起着重要作用。
例如,HF中血液流量减少的主要代偿机制之一是增加肾脏保留的盐和水的量。保留盐和水,而不是通过尿液排出,可增加血液中的血容量,并且有助于维持血压。然而,更大的血容量也会导致心肌,特别是心室增大。随着心腔增大,室壁厚度减小,心脏收缩减弱,导致心脏功能呈螺旋式下降。另一种代偿机制是动脉系统的血管收缩,它会升高血压以帮助维持足够的灌注,从而增加心脏必须泵送的负荷。
在低射血分数(“EF”)心力衰竭中,心脏中的高压是由于身体试图维持足够外周灌注所需的高压所致。然而,随着心脏因如此高的压力而变弱,这种疾病会加剧。左心房内的压力可能超过25mmHg,在这一阶段,流经肺循环系统的血液中的液体渗出或流出肺毛细血管,进入肺间质间隙和肺泡,导致肺充血,如果不治疗,则出现急性肺水肿综合征和死亡。
表1列出了正常心脏和患有HF的心脏的右心房压力(“RAP”)、右心室压力(“RVP”)、左心房压力(“LAP”)、左心室压力(“LVP”)、心输出量(“CO”)和每搏量(“SV”)的典型范围。在70次/分钟左右的正常心脏跳动中,维持正常心输出量所需的每搏量约为60至100毫升。当心脏的前负荷、后负荷和收缩力正常时,达到正常心输出量所需的压力列于表1。在患有HF的心脏中,血流动力学参数发生变化(如表1所示)以维持外周灌注。
表1
参数 | 正常范围 | HF范围 |
RAP(mmHg) | 2-6 | 6-20 |
RVSP(mmHg) | 15-25 | 20-80 |
LAP(mmHg) | 6-12 | 15-50 |
LVEDP(mmHg) | 6-12 | 15-50 |
CO(liters/minute) | 4-8 | 2-6 |
SV(milliliters/beat) | 60-100 | 30-80 |
HF通常分为收缩性心力衰竭(“SHF”)或舒张性心力衰竭(“DHF”)。在SHF中,心脏的泵送作用减小或减弱。一种常见的临床测量方法是射血分数,它是从左心室排出的血液(每搏量)除以舒张末期或舒张期左心室最大容积的函数。正常射血分数大于50%。收缩性心力衰竭通常会导致射血分数低于40%。这类患者有射血分数降低的心力衰竭(“HFrEF”)。HFrEF患者通常会有较大的左心室,这是因为一种称为“心脏重塑”的现象是由较高的心室压力引起的。
在DHF中,心脏通常正常收缩,射血分数正常,但比健康心脏在放松和充满血液时更硬,或顺应性更低。这类患者据说患有射血分数保留的心力衰竭(“HFpEF”)。这种僵硬可能阻碍血液充盈心脏,并且使血液回流到肺部,从而导致肺静脉高压和肺水肿。HFpEF在75岁以上的患者中更为常见,尤其是高血压女性。
这两种HF变体过去均采用药理学方法进行治疗,这通常包括使用血管扩张剂通过降低全身血管阻力来减少心脏的工作量,以及使用利尿剂来抑制液体积聚和水肿形成,并降低心脏充盈压力。目前还没有任何药物疗法可改进HFpEF的发病率或死亡率,而有几类药物对HFrEF患者的治疗产生了重要影响,包括肾素-血管紧张素拮抗剂、β受体阻滞剂和盐皮质激素拮抗剂。尽管如此,总体而言,HF仍然是一种进行性疾病,随着时间的推移,大多数患者的心功能和症状不断恶化。在美国,每年有超过100万人因HF严重恶化而住院,死亡率高于大多数癌症。
在HFrEF的更严重病例下,使用机械泵等辅助装置,通过执行通常由心脏完成的全部或部分泵送功能来降低心脏负荷。慢性左心室辅助装置(“LVAD”)和心脏移植常被用作最后手段。然而,这类辅助装置通常旨在提高心脏的泵送能力,以将心输出量增加到与正常生活相适应的水平,并且维持患者生命直到可获得供移植的供体心脏。这类机械装置能够推动大量血液(升/分钟),但是受到对电源、相对大的泵的需求的限制,并且存在溶血、血栓形成和感染的风险。还使用了临时辅助装置、主动脉内球囊和起搏装置。
已经开发出使用支架来改变给定血管内或心室之间的血压和流量的各种各样的装置。例如,授予Ruiz的美国专利第6,120,534号涉及用于调节通过身体血管或器官的液体流量的腔内支架,例如,用于调节通过肺动脉的血流以治疗先天性心脏缺陷。支架可包括可扩张的网状物,该网状物具有由收缩区域连接的叶状或圆锥形部分,该收缩区域限制通过支架的流动。网状物可包含由横向正弦或蛇形连接构件连接的纵向支柱。Ruiz对HF的治疗或左心房压力的降低保持沉默。
授予Amplatz等人的美国专利第6,468,303号描述了用于分流选定器官和血管的可折叠医疗装置和相关联方法。Amplatz描述,该装置可适用于分流患者心脏的隔膜缺损,例如,通过在患有左心发育不良综合征(“HLHS”)的新生儿的房间隔中产生分流。该专利还描述了增加肺静脉和全身静脉血液的混合可改进血氧含量,并且该分流管可在以后用闭塞装置封闭。Amplatz对HF的治疗或左心房压力的降低,以及调节通过该装置的血流速率的方法均保持沉默。
植入式心内分流装置已成功用于严重症状性心力衰竭患者。通过将血液从左心房(“LA”)转移或分流至右心房(“RA”),左心房内的压力降低或无法升高到原来的水平(左心房减压)。这一成就有望预防、缓解或限制与肺充血相关的症状、体征和综合征。这些包括严重的呼吸急促、肺水肿、缺氧、需要急性住院、机械通气和死亡。
分流流量通常由心房之间的压力梯度和分流装置的流体力学特性决定。后者通常受分流管的几何形状和材料组成的影响。例如,类似分流管设计的一般流动特性与平均室内压力梯度和有效孔口直径有关。
经皮植入房间分流管通常需要在插入分流管装置之前立即进行经中隔导管插入术。经中隔导管插入术系统从股静脉的入口位置开始,穿过卵圆窝(“FO”)区域的房间隔,该区域是房间隔的中心和最薄区域。这与先天性继发孔型房隔膜缺损(“ASD”)的大致位置相同。成人的FO长轴尺寸通常为15-20mm,并且厚度≤3mm,但在某些情况下,厚度可高达10mm。可使用本领域技术人员熟悉的许多不同技术来实现LA腔室接入,包括但不限于:针穿刺、管心针穿刺、螺旋针穿刺和射频消融。两个心房之间的通道扩张,以便于具有所需孔口尺寸/大小(size)的分流装置通过。扩张通常通过推进锥形护套/扩张器导管系统或血管成形术型球囊充气穿过FO来完成。
Dobak,III的美国专利出版物第2005/0165344号描述了用于治疗心力衰竭的装置,该装置包括具有栓子过滤器或阀门的管状导管,该装置被配置为位于心脏房间隔的开口中,以允许从左心房流入右心房。Dobak公开了血液分流可降低左心房压力,从而防止肺水肿和进行性左心室功能障碍,并且降低LVEDP。Dobak描述了该装置可能包括可展开的保持支柱,诸如对两侧的房间隔施加轻微的力并且将该装置夹在房间隔上的金属臂。
授予Nitzan的美国专利第9,034,034号(其全部内容通过引用并入本文)描述了一种分流管,其包含沙漏或空竹外形,具有最小化隔膜损伤的FO占地面积,这有望最小化血管翳生长和分流内腔的闭塞。它的单向阀也被设计用来减少反向分流和反常栓塞的可能性。分流管与隔膜和封装的可折叠镍钛诺框架接触的相对小的占地面积被设计成便于使用标准鹅颈圈套器和大孔护套从隔膜经皮取出和从身体取出,从而使装置更容易取出。空竹形状的文丘里管状内腔提供了更好的体积流量特性,从而与孔口-板分流管相比,在相同流量下允许更小的孔口。最后,FO上的小占地面积和沙漏形状经设计有助于在植入期间准确放置和保持。这种几何结构还最大限度地减少了对房间隔正常运动的干扰,并且小占地面积为需要经中隔导管插入术的其他潜在介入手术提供了分流管周围的空间。
由V-Wave有限公司(以色列凯撒利亚)制造的Nitzan设计的一个实施例被设计成支持从左向右的单向流动,包含由激光切割镍钛诺管构成的自膨胀框架。框架包括由六个纵向杆相互连接的五个正弦圆周支柱。框架是热定型的,因此它具有不对称的沙漏形状或空竹形状。分流管被部署成使得颈部(外径5.3mm)穿过FO,并且通过其外表面几何形状固定到位。分流管最宽的部分为锥形,分流管LA端外径约为14.3mm,用作入口漏斗远端的“入口”。入口漏斗位于左心房,并且将分流管的颈部配准到FO区域。第二个稍窄的钟形部分形成分流管的出口部分,其在分流管的RA端扩展至11.4mm的最大外径。分流管不需要法兰、圆盘或组织锚固件来固定到位。在不对邻近装置颈部的组织施加持续的压力、张力或摩擦接触的情况下,可实现隔膜保留。
V波分流管具有单个内腔,在该内腔中,流量被吸入LA中的入口漏斗中,并且通过内径为5.1mm的缩颈(类似文丘里孔口),然后通过位于分流管的RA端附近的生物瓣膜流出。入口漏斗和中心颈部区域用膨胀聚四氟乙烯(“ePTFE”)封装,以在框架上形成裙板或盖。裙板经设计用于促进层流,并且在装置愈合期间限制血管翳向内生长。出口钟形部分含有三个戊二醛固定的猪心包小叶,缝合在ePTFE包封的右心房范围的框架上。小叶经设计用于产生平滑的出口通道,并且保持在打开位置,仅当RA压力超过LA压力1–2mmHg时才关闭,从而防止从右向左的反向分流。
授予Eigler的美国专利第10,076,403号和第10,251,740号(其全部内容通过引用并入本文)描述了一种设计用于调节患者左心房和右心房之间的血压,同时防止血管翳的形成使分流管颈部区域的内腔变窄的房间分流管。
分流管的尺寸,例如血液在左心房和右心房之间流动的通道的直径,可能对患者的血流动力学和全身供氧产生不同的影响。例如,过小分流没有益处,而分流管过大可能会由于PAH患者的去饱和血液的过大混合而减少全身氧递送,或者在左心室HF患者中造成右侧容量超负荷和右心室衰竭。此外,每个患者的生理学均是独特的,因此,每个患者可能需要一个特定尺寸的房间分流管以获得最佳治疗。
因此,希望提供用于在将永久性分流管植入患者的房间隔内之前,为每个患者建立房间分流管并确定合适的可植入式分流管尺寸的装置和方法。
发明内容
本发明提供了用于控制穿过患者的房间隔的血流的系统、装置和方法。一种示例性装置包括具有近侧区域、远侧区域和其间的内腔的护套。护套的远侧区域包括第一组一个或多个开口和第二组一个或多个开口,第二组一个或多个开口与第一组一个或多个开口间隔开大于房间隔厚度的距离,使得第一组一个或多个开口设置在患者的第一心房内,而第二组一组一个或多个开口设置在患者的第二心房中。例如,护套的第二组一个或多个开口可具有圆形、椭圆形或矩形中的至少一个,或其任何组合。此外,护套的第二组一个或多个开口可关于护套的外表面对称或不对称地分布。
该装置还包括致动器,用于修改护套的第二组一个或多个开口的开口面积,使得血液响应于穿过房间隔的压力梯度,以与护套的第二组一个或多个开口的开口面积相对应的血流速率,经由第一组和第二组一个或多个开口以及其间的护套内腔而在第一和第二心房之间流动。例如,致动器可被致动以增量地选择护套的第二组一个或多个开口的开口面积,使得第一和第二心房之间的血流在每一增量处的血流速率与通过预定尺寸的患者的房间隔穿刺(例如,直径在4至8mm之间)的血流相对应。
此外,该装置可包括可移动地设置在护套的内腔内的内套管。内套管具有近侧区域和远侧区域,远侧区域的外径等于护套的内径。因此,致动器可被致动,以通过相对于护套移动内套管一个增量来改变护套的第二组一个或多个开口的开口面积,从而允许血液响应于穿过房间隔的压力梯度,以与护套的第二组一个或多个开口的开口面积相对应的血流速率,经由第一组和第二组一个或多个开口以及其间的护套内腔而在第一和第二心房之间流动。
此外,内套管还可包括一个或多个冲洗端口,该冲洗端口通过内套管的一个或多个冲洗内腔与冲洗液源流体连通。因此,一个或多个冲洗端口可通过其喷射冲洗流体,以防止血块积聚在护套的第二组一个或多个开口处。此外,内套管可包括经设定尺寸和形状以容纳导丝的导丝内腔。因此,该装置还可包括压力传感器导丝,该压力传感器导丝可设置在内套管的导丝内腔内。压力传感器导丝可操作地联接到外部控制器,并且可测量第一心房内的压力,并且将指示所测得压力的信号传输到外部控制器。
根据本发明的一个方面,可移动地设置在护套的内腔中的内套管具有与护套的第一组一个或多个开口流体连通的第一组一个或多个孔,以及在其间延伸的内腔。内套管还包括第二组一个或多个孔,其经设定尺寸和形状与护套的第二组一个或多个开口配准。因此,通过相对于护套移动内套管以将内套管的第二组一个或多个孔与护套的第二组一个或多个开口配准预定量,可致动致动器以改变护套的第二组一个或多个开口的开口面积,从而允许血液响应于穿过房间隔的压力梯度,以与内套管的第二组一个或多个孔和护套的第二组一个或多个开口之间的预定配准量相对应的血流速率,经由第一和第二组一个或多个开口和孔以及其间的内套管内腔而在第一和第二心房之间流动。
此外,护套还可包括与第二组一个或多个开口间隔开的第三组一个或多个开口,使得第三组一个或多个开口被设置在患者的下腔静脉内,而第一组一个或多个开口在装置操作期间被设置在第一心房内。因此,内套管还包括第三组一个或多个孔,其经设定尺寸和形状与护套的第三组一个或多个开口配准。因此,致动器可被致动以相对于护套移动内套管,以便将内套管的第三组一个或多个孔与护套的第三组一个或多个开口配准预定量,从而允许血液响应于下腔静脉和第一心房之间的压力梯度,经由第一组和第三组一个或多个开口和孔以及其间的内套管内腔而在下腔静脉和第一心房之间流动。例如,当第三组一个或多个孔与套管的第三组一个或多个开口完全配准时,内套管的第二组一个或多个孔未与护套的第二组一个或多个开口配准,使得允许血液在下腔静脉和第一心房之间流动,但不允许血液在第二心房和下腔静脉之间流动。
该装置还可包括一个或多个传感器,该一个或多个传感器设置在护套的内腔内,并且可操作地联接至外部控制器。外部控制器可包括显示器和/或用户界面,使得医生可手动操作该装置。一个或多个传感器可测量一个或多个生理参数,例如,压力、血流速率、血流速度或血氧含量,并且将指示所测得生理参数的信号传输到外部控制器。此外,该装置可包括设置在护套的远侧区域的锚固件,以便于将护套固定到患者的房间隔。例如,锚固件可为可在第一心房内充气的球囊,从而防止护套相对于患者的房间隔的近侧移动。另选地,锚固件可为可在第二心房内充气的球囊,从而防止护套相对于患者的房间隔的远侧移动。在一个实施例中,锚固件可包括第一心房中的第一球囊和第二心房中的第二球囊,使得当充气时,球囊夹住房间隔。此外,(一个或多个)球囊可包括设置在其外表面上的金属线圈,用于传输足以消融与金属线圈相邻的组织的射频能量。另选地或附加地,锚固件可包括经设定尺寸和形状适合于在房间隔壁上配准的展开尖齿。
根据本发明的一个方面,该装置可包括设置在护套外表面上的金属线圈。例如,金属线圈可被设置在靠近第二组一个或多个开口的护套的外表面上。金属线圈可发射足以消融邻近金属线圈的组织的射频能量,以诱导房间分流管。
在一个实施例中,该装置可包括一个或多个附加金属线圈,使得金属线圈中的每一个可发射足以消融邻近相应金属线圈的组织的RF能量,以诱导具有预定直径的房间分流管。例如,护套的分级部分可具有外表面,该外表面具有在远侧方向增加的横截面积,使得金属线圈中的每一个沿护套的分级部分设置在对应于预定直径的位置处。
根据本发明的另一方面,提供了一种用于控制穿过患者的房间隔的血流的方法。该方法可包括穿过患者的房间隔产生穿刺;穿过穿刺递送护套,使得护套的第一组一个或多个开口设置在患者的第一心房内,而护套的第二组一个或多个开口设置在患者的第二心房内;允许血液响应于穿过房间隔的压力梯度,经由第一组和第二组一个或多个开口和护套的内腔而在第一和第二心房之间流动;修改第二组一个或多个开口的开口面积,使得允许血液以修改后的血流速率经由第一组和第二组一个或多个开口以及护套的内腔而在第一和第二心房之间流动;以及基于允许和修改选择用于植入患者的房间隔的房间分流管。
例如,修改第二组一个或多个开口的开口面积可包括将护套的内腔内的内套管移动一个增量,使得允许血液以与第二组一个或多个开口的开口面积相对应的血流速率,经由护套的第一组一个或多个开口以及设置在护套的第二组一个或多个开口与内套管的远侧区域之间的开口而在第一和第二心房之间流动。
此外,该方法可包括发射射频能量以消融穿刺周围的组织以改变组织愈合。例如,发射射频能量以消融穿刺周围的组织可诱发具有预定直径的房间分流管。因此,该方法还可包括相对于房间隔移动护套,以使房间隔与设置在护套外表面上的金属线圈对齐,使得发射射频能量以消融穿刺周围的组织包括经由金属线圈发射射频能量以消融穿刺周围的组织以诱导具有预定直径的房间分流管。
当患者患有肺动脉高压时,允许血液响应于穿过房间隔的压力梯度,经由护套和护套的内腔的第一和第二组一个或多个开口而从右心房内流向左心房。当患者患有心力衰竭时,允许血液响应于穿过房间隔的压力梯度,经由护套和护套的内腔的第一和第二组一个或多个开口而从左心房内流向右心房。
该方法还包括测量第一和第二心房之间血流的血流速率,和/或在第二组一个或多个开口的开口的每个增量面积/增量区域(incremental area)测量患者的至少一个生理参数。根据本发明的一个方面,可将指示所测得生理参数的信号传输到外部控制器或显示器。在本发明的另一方面中,可通过单独的系统来测量患者的至少一个生理参数,诸如心脏超声机、脉搏血氧计、心电图、血压计或患者生理学领域的技术人员已知的血流动力学监测形式。因此,所提供的可植入式房间分流管可基于指示所测得生理参数的信号在其颈部区域处具有预选直径。
附图说明
图1A示出了根据本发明的原理构造的用于临时精确分流的示例性装置。
图1B是包括图1A的装置的示例性系统的示意图。
图2A示出了根据本发明的原理构造的图1的装置的示例性护套。
图2B示出了根据本发明的原理构造的替代示例性护套。
图2C示出了根据本发明的原理构造的另一替代示例性护套。
图3A至3D示出了根据本发明的原理构造的护套的一个或多个开口的各种配置。
图4A示出了根据本发明的原理构造的图1的装置的示例性内套管,而图4B示出了图4A的内套管的冲洗端口。
图4C示出了根据本发明的原理构造的替代示例性内套管。
图5A和5B示出了根据本发明的原理构造的图1的装置的示例手柄。
图6是根据本发明的原理的用于精确控制穿过患者的房间隔的血流的示例性方法步骤的流程图。
图7A至7I示出了根据本发明的原理的图6的示例性方法的步骤。
图8示出了根据本发明的原理构造的另一替代示例性护套。
图9示出了根据本发明的原理构造的具有两个锚固件的另一替代示例性护套。
图10示出了具有根据本发明的原理构造的分级部分的另一替代示例性护套。
具体实施方式
诸如V-Wave有限公司(以色列凯撒利亚)制造的房间分流管可用于将血液从一个心腔重新分配到另一个心腔,以解决心力衰竭、心肌梗死和肺动脉高压(PAH)等病理问题。例如,在肺动脉高压患者中,房间分流管允许血液从右心房穿过房间隔流向左心房,以治疗急性右心室心力衰竭。正确尺寸的分流管将使右心室减压并改进全身氧递送,然而,过小的分流管的益处微乎其微,而过大的分流管会由于过多的去饱和血液混合物而减少全身氧递送。
在左心室HF患者中,房间分流管允许血液从左心房穿过房间隔流向右心房,以治疗急性左心室心力衰竭,所述急性左心室心力衰竭是由于例如慢性HF的恶化或急性心肌梗塞等损伤后LV的急性失代偿引起的,所述急性心肌梗塞导致严重的泵衰竭或急性二尖瓣反流,诸如伴随乳头肌功能障碍或腱索断裂而发生的。正确尺寸的分流管将使左心室和左心房减压,缓解肺充血,而不会造成RV容量超负荷,然而,过小的分流管可能只有极小的益处,而过大的分流管可能导致右侧容量超负荷和RV衰竭。
在更稳定的PAH或慢性HF的患者中,在临时精确分流期间获得的关于血流动力学反应的信息可用于指导永久性房间分流的尺寸,无论是通过放置植入式房间隔装置还是创建一个医源性隔膜缺损。
现在参考图1A,提供了用于临时精确分流的示例性护套分流原型装置,例如装置10。装置10包括近侧区域12和远侧区域14,近侧区域12和远侧区域14经设定尺寸和形状以在患者体内递送,例如,在两个心腔(诸如左心房和右心房)之间递送。装置10包括护套20和可移动地设置在护套20内腔内的内套管40。护套20可包括锚固件30,用于在装置10的操作期间相对于患者的房间隔来固定护套20,如下面进一步详细描述的。
护套20和内套管40从装置10的远侧区域14延伸到近侧区域12,在近侧区域12中护套20和内套管40操作性地联接到患者身体外部的致动器50。致动器50,例如手柄,可被选择性地致动,以相对于护套20增量地移动内套管40,从而根据穿过房间隔的压力梯度,精确地控制允许从一个心腔到另一个心腔流过护套20的血流的量和速率。因此,装置10可模拟与通过各种尺寸的房间分流管的血流相对应的血流。可监测患者对各种尺寸分流模拟的血流动力学反应,以确定特定患者的最有效分流尺寸。例如,通过装置10在体内测量的流速与通过各种尺寸的房间分流管的相应流速之间的相关性可基于各种压力梯度下的一系列体外比较模拟。此外,相关性可在查找表中表示和/或存储在外部控制器的存储器中。
例如,如图1B所示,装置10还可包括联接到护套20(例如,设置在护套20的内腔内)的一个或多个传感器21,以用于测量一个或多个生理参数,包括压力、血流速率、血流速度或血氧含量中的至少一个。传感器21生成指示(一个或多个)所测得生理参数的(一个或多个)信号并将其传输到操作地联接到一个或多个传感器21的外部控制器55。控制器55可基于(一个或多个)所测得生理参数存储和监测患者的血流动力学,以便医生可确定最适合每个特定患者的分流管尺寸。例如,控制器55可将期望患者血流动力学的预定阈值存储在控制器55的存储器中,使得控制器55可将每个模拟分流管尺寸下的(一个或多个)所测得生理参数与预定阈值进行比较,以确定哪个分流管尺寸将为患者提供最期望的结果。
现在参考图2A,提供了示例性护套20。护套20可由生物相容性聚合物(例如Pebax、尼龙等)或高密度聚乙烯(“HDPE”)制成。优选地,护套20由Pebax制成。护套20可具有不透射线标记带,用于在护套20递送到(例如)患者的房间隔期间进行最佳定位验证。护套20具有用于与致动器50联接的近侧区域22,以及经设定尺寸和形状以定位在患者体内的远侧区域24,例如,穿过患者的房间隔的穿刺。根据本发明的一个方面,护套20可具有锥形几何形状,使得护套20的近侧区域22的外径小于护套长度的其余部分,例如护套20的远侧区域24。因此,沿护套20的外径尺寸的差异可最小化对进入部位的创伤,并且可能允许更长的导管停留时间。另选地,护套20以及相应的内套管可具有从近侧区域22到远侧区域24的恒定直径。
如图2A所示,护套20在其远端具有第一组一个或多个开口26,以及第二组预切割特征,例如,在靠近第一组一个或多个开口26的位置沿护套20设置的一个或多个开口28。第二组一个或多个开口28与第一组一个或多个开口26的距离大于房间隔的厚度,使得当一个或多个开口26设置在例如第一心房中时,一个或多个开口28设置在例如第二心房中。例如,一个或多个开口26可设置在患者的左心房内,而一个或多个开口28设置在患者的右心房内,反之亦然。一个或多个开口28通过护套20的内腔与护套20的一个或多个开口26流体连通,从而当一个或多个开口28未被阻塞时(如下面进一步详细描述的),允许血液响应于穿过房间隔的压力梯度,经由一个或多个开口26和28而在患者的右心房和左心房以及护套的内腔之间流动。例如,在PAH患者中,允许血液从患者的右心房通过一个或多个开口28的开口流入护套的内腔,并且通过一个或多个开口26流出;而在左心室HF患者中,允许血液从患者左心房流出,通过一个或多个开口26流入护套的内腔,并且通过一个或多个开口28的开口流出。
在另一个实施例中,护套可由聚合物制成,该聚合物能够使其在球囊充气时径向膨胀,从而能够增加分流的血流。因此,护套可通过护套的后续充气/放气进行进一步调节。此外,护套20可在传统的标准经中隔导管插入术之后通过导丝经由右股静脉递送。另选地,一旦通过其他方式建立到左心房的导丝通路,护套20可经由静脉接入部位递送。
如图2A所示,护套20可包括锚固件30,例如隔膜固定元件,用于在装置10操作期间相对于例如患者的房间隔来锚固护套20,以在内套管40缩回期间稳定护套20。例如,锚固件30可为安装在远侧区域24处的护套20的外表面上的充气球囊。球囊30可具有腰部,用于在房间隔上自配准。球囊30可经由与球囊的内部空间和流体充气源流体连通的护套20的充气内腔充气。球囊30能够将护套20固定在目标部位处,并且确保护套20相对于房间隔的最佳定位,例如,一个或多个开口26位于LA中部,一个或多个开口28位于RA中部。球囊30可充气,以使其设置在房间隔的一侧,或者另选地,设置在房间隔的两侧上,以使球囊夹在房间隔中以改进固定,如下文关于图9的进一步详细描述的。例如,当球囊30被充气以使球囊30完全位于患者右心房内时,护套20将被阻止向患者左心房的远侧移动。另选地,当球囊30被充气以使球囊30完全位于患者的左心房内时,护套20将被阻止向患者的右心房近侧移动。如本领域普通技术人员将理解的,球囊30可被相应地设定尺寸和形状,以将护套20锚固在房间隔的穿刺内。
根据本发明的另一个方面,锚固件30可包括一系列隔膜固定元件,例如可展开尖齿,其被设计成在收缩的递送状态下递送到房间隔,并且在例如引入护套缩回时膨胀到膨胀的展开状态,以将护套20锚固到房间隔。其他隔膜固定元件可固定在护套20的远侧区域,以将护套20固定在房间隔上,例如,包括授予Keren的美国专利第9,943,670号、第8,328,751号和第8,091,556号、授予Rottenberg的美国专利第9,724,499号和第8,070,708号以及授予Levi的美国专利第9,681,948号中所述的隔膜固定元件,其中每一个专利的全部内容通过引用并入本文。
根据本发明的一个方面,护套20可具有设置在其外表面上的能够传输射频能量的金属线圈31,用于消融患者卵圆窝内的穿刺轮廓。如图2A所示,线圈31可设置在球囊30的外表面上,从而形成诸如在例如授予Hara的美国专利第5,578,008号和授予Satake的美国专利申请第2010/0069836号中描述的热球囊,这些专利的全部内容通过引用并入本文中。因此,球囊30可用于加热在房间隔内形成穿刺轮廓的组织,以消融组织,从而改变组织愈合,以防止或限制响应于机械损伤的增殖组织向内生长。
现在参考图2B,提供了替代示例性护套。护套20'的构造类似于图2A的护套20,其中类似部件由类似的带撇号的附图标记标识。例如,近侧区域22'与近侧区域22相对应,远侧区域24'与远侧区域24相对应,一个或多个开口26'与一个或多个开口26相对应,并且一个或多个开口28'与一个或多个开口28相对应。护套20'与护套20'的不同之处在于护套20'不包括设置在远侧区域24'上的任选锚固件30。如本领域普通技术人员将理解的,护套以及相应的内套管可具有从近侧区域到远侧区域的恒定直径。
现在参考图3A至3D,提供了护套的第二组一个或多个开口的预切割特征的各种配置。一个或多个开口28、28'可具有选自椭圆形、圆形、矩形等适于提供最小的流动阻力(即低剪应力和低湍流)并且通过使一个或多个开口逐渐暴露在致动器50的致动下来控制流量的形状,如下面进一步详细描述的。可选择一个或多个开口的设置和布置以优化流动,以及维持护套的结构完整性和功能性。一个或多个开口可使用激光切割、机械穿刺等制造。根据本发明的一些方面,一个或多个开口可包括网状物,例如,由镍钛合金丝的非常薄的编织物制成,以防止栓子通过其中。
如图3A所示,一个或多个开口32具有椭圆形,并且以线圈状模式沿护套的远侧区域分布,使得一个或多个开口中的至少一个开口比一个或多个开口中的另一个开口更靠近。如图3B所示,一个或多个开口34可具有圆形,并且如图3C所示,一个或多个开口36可具有矩形。如图3C所示,一个或多个开口36可沿垂直于护套的纵向轴线的单个平面均匀分布。开口可围绕护套20的外表面对称或不对称分布。如图3D所示,护套包括围绕护套圆周均匀分布的四个纵向开口38(两个开口未示出)。如本领域普通技术人员所理解的,与图3A至3D所示相比,可沿护套的远侧区域形成更多或更少的开口。
现在参考图4A和4B,提供示例性内套管40。内套管40可由生物相容性聚合物(例如Pebax、尼龙等)或高密度聚乙烯(“HDPE”)制成。优选地,内套管40由Pebax制成。此外,内套管40可具有足以在穿过房间隔设置在护套20内时在房间隔内维持穿刺的刚度。内套管40可具有不透射线标记带,以便在将内套管40定位在护套20的内腔内时进行最佳定位验证。内套管40具有用于与致动器50联接的近侧区域42,以及经设定尺寸和形状以便可移动地设置在护套20的内腔内的远侧区域44。
如图4A和4B所示,内套管40可具有设置在远侧区域44处并且与患者身体外部的冲洗液源流体连通的一个或多个冲洗端口46。因此,在装置10操作期间,冲洗流体可经由一个或多个冲洗端口46喷射,以防止血凝块积聚在护套20的一个或多个开口26和/或一个或多个开口28处。此外,内套管40可具有导丝内腔47,用于在将内套管40递送到护套20内期间在其中接收导丝。
内套管40可具有与上述护套20相对应的锥形几何形状。因此,当护套和内套管均具有相应的锥形几何形状时,如图2C所示,护套20”可包括沿护套20”邻近锥形部分的一个或多个通风口29,例如,一个或多个开口,以允许流体流入或流出两个锥形管护套20”和内套管40'之间的变化容积。此外,如图4A所示,内套管40可包括沿内套管40定位在锥形部分的近侧部分上并且与患者体外的冲洗流体源流体连通的一个或多个冲洗通风口45,例如,一个或多个开口。因此,在装置10操作期间,冲洗流体,例如肝素化盐水,可通过一个或多个冲洗通风口45喷射,以防止血栓积聚在护套20”的一个或多个通风口29处。另选地,在护套从近侧区域到远侧区域具有恒定直径的实施例中,如上所述,内套管40也可具有从近侧区域42到远侧区域44的恒定直径。
通过比较图2C和图4A,一个或多个冲洗通风口45可围绕内套管40周向定位,使得一个或多个冲洗通风口45与护套20”的一个或多个通风口29周向相对,以允许内套管40和护套20”之间的空间进行更完整的冲洗。因此,一个或多个通风口29和一个或多个冲洗通风口45将允许在内套管40远侧尖端处的一个或多个冲洗端口46和一个或多个冲洗通风口45之间流动。一个或多个通风口29和一个或多个冲洗通风口45可具有比一个或多个开口28”更小的开口面积,并且可在第一和第二心房之间呈现小的恒定基线流量,因此基线流量可被包括在装置10的校准中。
再次参考图4A和4B,内套管40的至少远侧区域44的外径基本上等于护套20的至少远侧区域24的内腔内表面的直径,使得血液不会在内套管40的外表面和护套20的内表面之间流动。因此,当内套管40位于邻近一个或多个开口28的护套20的内腔内时,一个或多个开口28的开口被阻塞,并且不允许血液通过一个或多个开口28进入。此外,当内套管通过致动器50相对于护套20向近侧移动时,一个或多个开口28的开口面积从完全阻塞到完全暴露逐渐增加。因此,可精确地选择一个或多个开口28的开口面积,以允许血液响应于穿过房间隔的压力梯度,以预定的血流速率经由一个或多个开口28、一个或多个开口26的开口面积和护套20的内腔而在第一和第二心房之间流动。此外,一个或多个开口28的开口的选定面积对应于特定尺寸的分流管,例如,在分流管颈部区域的通道处直径等于(例如)4mm、4.5mm、5mm、5.5mm、6mm、6.5mm、7mm、7.5mm或8mm的房间分流管。为了模拟通过较大的室间分流管(例如直径大于7mm)的血流,手柄接合的变化可用于更大的直径相关性。如本领域普通技术人员将理解的,护套的一个或多个开口的开口的选定面积可对应于分流管颈部区域的通道处的直径,并且不限于0.5mm增量。
现在参考图4C,提供了替代示例性内套管。内套管40'的构造类似于图4A的内套管40,其中类似部件由类似的带撇号的附图标记标识。例如,近侧区域42'与近侧区域42相对应,而远侧区域44'与远侧区域44相对应。内套管40'与内套管40'的不同之处在于,内套管40'在其远端处具有第一组一个或多个孔48,以及第二组预切割特征,例如,在靠近一个或多个孔48的位置处沿内套管40'设置的一个或多个孔49。
一个或多个孔49通过内套管40'的内腔与内套管40'的一个或多个孔48流体连通,当内套管40'位于护套20的内腔内时,一个或多个孔48与护套20的一个或多个开口26流体连通,从而允许血液响应于穿过房间隔的压力梯度,根据一个或多个开口28和一个或多个孔49之间的配准量,经由一个或多个开口28和一个或多个孔49、一个或多个开口26、一个或多个孔48以及内套管的内腔和护套的内腔之间的开口而在第一和第二心房之间流动。
一个或多个孔49经设定尺寸和形状以与护套20的一个或多个开口28配准。例如,内套管40'最初可定位在护套20内,使得一个或多个孔49和一个或多个开口28完全不配准,从而防止血液流过护套20的一个或多个开口28的开口,因为一个或多个开口28被内套管40'的主体完全阻塞。此外,当内套管40'相对于护套20向近侧移动时,随着一个或多个孔49开始与一个或多个开口28配准,内套管40'的内腔和RA之间的开口面积增加。如本领域普通技术人员所理解的,配准一个或多个开口28和一个或多个孔49所需的内套管40'相对于护套20的运动方向取决于一个或多个开口28相对于一个或多个孔49的位置。例如,如果在操作位置一个或多个开口28位于一个或多个孔49的远侧,内套管40'的远侧运动将允许一个或多个开口28和一个或多个孔49配准。
因此,允许血液响应于穿过房间隔的压力梯度,经由一个或多个开口28的开口而在第一和第二心房之间流动,所述一个或多个开口28的开口由一个或多个开口28和一个或多个孔49、护套20的一个或多个开口26、内套管40’的一个或多个孔48以及护套20和内套管40'的内腔之间的配准产生。内套管40'可增量移动,使得内套管40'相对于护套20的每个选定位置提供一个或多个开口28的开口的预定区域,该预定区域与特定的房间分流管尺寸相对应。当一个或多个孔49与一个或多个开口28完全配准时,装置10模拟通过最大尺寸的分流管(例如8mm)的血流。
现在参考图5A和5B,提供了示例性致动器。致动器50可以是经设定尺寸和形状以由患者身体外部的医生轻松地控制的手柄,并且包括非常精确的机构来控制内套管40在护套20内的缩回或前进。致动器50可操作地联接到护套20和内套管40的近侧区域,使得致动器50的致动相对于护套20的远侧区域24增量地移动内套管40的远侧区域44。分流的血容量可通过致动器50上的预设功能转换为有效分流直径。如图5A所示,致动器50可包括第一致动器52(例如开关)和第二致动器54(例如可旋转旋钮)。第一致动器52操作性地联接到内套管40,使得第一致动器52的致动(例如,第一致动器52相对于致动器50的缩回)导致内套管40相对于护套20移动预定距离。例如,在初始起始位置,第一致动器52位于致动器50的远侧部分,并且用作护套20内的扩张器。因此,内套管40定位在护套20内,使得由于内套管40阻塞了一个或多个开口28的开口,因此不允许血液流过护套20的一个或多个开口28。
然后,第一致动器52可沿致动器50移动到靠近初始起始位置的第二操作位置,从而使内套管40相对于护套20移动预定距离。在第二操作位置,内套管40的远端位于护套20的一个或多个开口28附近,但不暴露一个或多个开口28的任何开口,从而防止血液从中流过。因此,在第一致动器52致动时,装置10准备好使用。此外,致动器50可包括用于向医生提供当前模拟分流管尺寸的视觉指示的标记56。
现在参考图5B,示出了致动器50沿图5A的线A-A的横截面图。如图5B所示,第二致动器54可具有对应于致动器50的螺纹部分的螺纹部分58,使得第二致动器54的旋转相对于护套20精确且逐渐地移动内套管40。因此,护套20的长度可相对于致动器50固定,而内套管40通过第二致动器54的致动相对于护套20向近侧或远侧移动,以露出或堵塞护套20的一个或多个开口28。例如,在第一致动器52从初始启动位置移动到第二操作位置之后,第二致动器54可随后被致动,以相对于护套20逐渐增量地移动内套管40,从而逐渐增加护套28的一个或多个开口28的开口面积,以允许血液流过其中。
现在参考图6,提供了根据本发明的原理使用图1A的装置10精确控制穿过患者的房间隔的血流的示例性方法60的步骤。方法60的一些步骤可通过参考图7A-7I进一步阐述。此外,为了下文论述的目的,将描述方法60以精确控制从患者右心房穿过房间隔到患者左心房的血流,例如以治疗PAH;然而,如本领域普通技术人员将理解的,方法60可用于精确控制从患者左心房穿过房间隔到患者右心房的血流,例如,根据穿过房间隔的压力梯度治疗LVHF。此外,方法60可用于促进血液从一个心腔流向另一个心腔。
在步骤61,使用本领域已知的技术,例如授予Yacoby的美国专利第9,713,696号中所述的技术,穿过患者的房间隔(例如穿过患者的卵圆窝)进行穿刺,其全部内容通过引用并入本文。因此,导丝可以穿过房间隔的穿刺输送,并且在步骤62,护套20穿过导丝并穿过房间隔的穿刺递送,使得一个或多个开口26设置在第一心房内,例如左心房,并且一个或多个开口28设置在第二心房内,例如,右心房,如图7A所示。内套管40设置在护套20的内腔内,使得内套管40用作扩张器,并且护套20和内套管40通过内套管40的导丝内腔47在导丝上前进。金属线圈31可用于发射射频能量,以加热构成房间隔的穿刺轮廓的组织,从而消融组织并改变组织愈合,以防止或限制组织响应于机械损伤而增殖。
在步骤63,护套20可选择性地锚固至房间隔,诸如通过在左心房内膨胀球囊30,从而防止护套20相对于患者的房间隔的向近侧移动,如图7B所示。如上所述,可使用不同形状的球囊将护套20固定在房间隔穿刺内。例如,球囊可具有狗骨形状,使得球囊的腰部接触房间隔的穿刺的轮廓,同时球囊的相对侧充气以将房间隔夹在其间。因此,金属线圈31可设置在球囊的腰部上,并且被致动以发射射频能量以消融周围组织,从而改变球囊腰部附近的组织愈合。当使用护套20'时,可跳过步骤63,和/或可使用锚固护套的其他手段。此外,如上所述,可使用替代或附加的隔膜固定元件,例如可展开尖齿,可用于将护套20锚固到房间隔。
在步骤64,致动器50使内套管40在护套20内向近侧移动,以修改护套20的一个或多个开口28的开口面积。例如,如图7C所示,可将第一致动器52从初始起始位置近距离移动到第二操作位置。当第一致动器52处于第二操作位置时,第二致动器54随后可被致动,以相对于护套20增量地移动内套管40,如图7D所示。具体而言,图7D示出了当第二致动器54已经旋转,使得标记56从指示一个或多个开口28完全阻塞且因此没有血液从右心房通过一个或多个开口28流入左心房的初始位置移动到沿致动器50的位置,该位置指示一个或多个开口28的最小开口以允许血液流过,对应于例如,4mm的房间分流管。此外,第一致动器52还可用作安全锁,使得第二致动器54可不被致动,直到第一致动器52被致动到第二操作位置。
因此,第二致动器54随后可被致动,以相对于护套20增量地移动内套管40,如图7E至7G所示。例如,如图7E所示,可旋转第二致动器54,直到标记56指示一个或多个开口28的开口面积允许血液以与通过4.5mm房间分流管的血流相对应的血流速率在右心房和左心房之间流过。如图7F所示,可进一步旋转第二致动器54,直到标记56指示一个或多个开口28的开口面积允许血液以与通过5mm房间分流管的血流相对应的血流速率在右心房和左心房之间流过。如图7G所示,可进一步旋转第二致动器54,直到标记56指示一个或多个开口28的开口面积允许血液以与通过5.5mm房间分流管的血流相对应的血流速率在右心房和左心房之间流过。如本领域普通技术人员将理解的,致动器50可被致动以模拟通过更小或更大的房间分流管(例如,3.5mm分流管、6mm分流管、6.5mm分流管、7mm分流管、7.5mm分流管和8mm分流管等)的血流。
如上所述,一个或多个开口28的开口面积可被测量为一个或多个开口28与内套管40的主体之间的空间,或护套20的一个或多个开口28与内套管40'的一个或多个孔49之间的配准空间。此外,为患者选择哪种尺寸的分流管的决定可能基于从比较性体外台架试验或体内试验得出的转换查找表。
此外,在步骤65,可通过在装置10操作期间测量一个或多个开口28的开口的每个增量面积的患者生理参数来监测患者的血流动力学。例如,一个或多个传感器21可测量一个或多个生理参数,包括压力、血流速率、血流速度或血氧测定中的至少一个,以确定治疗的有效性,例如,关于房间压力、心输出量、血液饱和度等。传感器21还可生成指示用于传输到外部控制器55以进行监测的所测得生理参数的(一个或多个)信号。另选地或附加地,用于递送护套20和内套管40的导丝可为操作地联接到外部控制器55的压力传感器导丝,用于测量第一心房内的压力,并且生成指示所测得压力的信号以传输到外部控制器55。因此,外部控制器55可将所测得生理参数与存储的期望阈值进行比较,并且显示这类结果,使得医生可确定哪种尺寸的分流管最适合每个患者。
在步骤66中,医生基于患者的响应于致动器50的每个致动增量的监测的血流动力学,选择要植入特定患者的房间隔穿刺内的特定尺寸的房间分流管。例如,如图7H所示,医生可在第一区域72和第二区域74之间的颈部区域76处具有5mm直径的分流管70、第一区域82和第二区域84之间的颈部区域86处具有5.5mm直径的分流管80以及第一区域92和第二区域94之间的颈部区域96处具有6mm直径的分流管90之间进行选择,用于植入患者体内。如本领域普通技术人员将理解的,可选择更小或更大的房间分流管用于植入,包括,例如,4.5mm分流管、6.5mm分流管、7mm分流管、7.5mm分流管或8mm分流管。因此,如图7I所示,可经由授予Keren的美国专利第8,091,556号、授予Yacoby的美国专利第9,713,696号、授予Eigler的美国专利第10,076,403号中所述的方法和递送工具,将选定的房间分流管(例如,分流管70)植入患者的房间隔AS内,专利中的每一个的全部内容通过引用并入本文。另选地,护套20和内套管40可从致动器50分离,并且根据需要在患者体内保留一段时间,直到移除。
实验结果
本节所述的试验是在稳定顺流试验条件下,在沙漏形房间分流管(由以色列凯撒利亚V-Wave有限公司制造)和护套分流管原型装置上进行的。本试验的目的是比较通过5mm和6mm房间分流管的流速,并且证明这些流速与通过护套分流原型装置的致动器上两个相应设置的流速之间的相关性。如下表2所示,两者之间存在良好的相关性,在各种房间压力梯度条件下,最大偏差范围为1%至10%。
表2
根据本发明的另一方面,护套可包括三组一个或多个开口,如图8所示。
图8的护套20”'的构造类似于图2A的护套20,其中类似部件由类似的带三重撇号的附图标记标识。例如,近侧区域22”'与近侧区域22相对应,远侧区域24”'与远侧区域24相对应,一个或多个开口26”'与一个或多个开口26相对应,并且一个或多个开口28”'与一个或多个开口28相对应。护套20”'与护套20的不同之处在于护套20”'包括第三组一个或多个开口33。
第三组一个或多个开口33可定位在护套20”'上的与第一组和第二组一个或多个开口26”'、28”'间隔开的位置处,使得当第二组一个或多个开口28”'设置在右心房内时,第三组一个或多个开口33设置在患者肾静脉上方的下腔静脉内。因此,当内套管进一步缩回时,第三组一个或多个开口33可暴露,而第二组一个或多个开口28”'被堵塞,从而允许血液响应于下腔静脉和左心房之间的压力梯度,经由第三组一个或多个开口33而不是第二组一个或多个开口28”'流动。这可通过使用类似于内套管40'构造的内套管来实现,该内套管具有与护套20”'的第一组一个或多个开口26”'流体连通的第一组一个或多个孔,经设定尺寸和形状以与护套的第二组一个或多个开口28”'配准的第二组一个或多个孔,以及经设定尺寸和形状以与护套的第三组一个或多个开口33配准的第三组一个或多个孔。
例如,当护套20”'的第二组一个或多个开口28”'与内套管的第二组一个或多个孔完全配准时,护套20”'的第三组一个或多个开口33根本不与内套管的第三组一个或多个孔配准,并且当护套的第二组一个或多个开口28”'根本不与内套管的第一组一个或多个孔配准时,护套20”'的第三组一个或多个开口33与内套管的第三组一个或多个孔配准。
内套管的第二组和第三组一个或多个孔可间隔开足够的距离,使得血液一次只能经由护套20”'的第二组一个或多个开口28”'或第三组一个或多个开口33进入。由于来自下腔静脉的静脉回流因为肾脏提取的氧较少而相对富含氧,因此与源自第二组一个或多个开口的类似尺寸的分流管相比,这种分流的血液源将导致全身氧饱和度的下降更小。这可能更有利于治疗急性RV失代偿。
现在参考图9,提供了具有双锚固件的替代示例性护套。护套20””类似于图2A的护套20构造,其中相似的部件由相似的带四重撇号的附图标记标识。例如,近侧区域22””与近侧区域22相对应,远侧区域24””与远侧区域24相对应,一个或多个开口26””与一个或多个开口26相对应,一个或多个开口28””与一个或多个开口28相对应,并且球囊30””与球囊30相对应。护套20””与护套20的不同之处在于护套20””包括设置在靠近球囊30””的护套20””的远侧区域24””上的第二球囊35。相应地,球囊35可充气,使球囊35完全位于患者的右心房内,并且球囊30””可充气,使球囊30””完全位于患者的左心房内,因此,充气球囊30””和35可夹在房间隔中间以改进固定,从而防止相对于房间隔的近侧和远侧运动。如本领域普通技术人员将理解的,与图2A的球囊30一样,球囊30””和/或球囊35可具有设置在其上的金属线圈。
现在参考图10,提供具有分级部分的另一替代示例性护套。护套100的构造类似于图2B的护套20'。例如,近侧区域102与近侧区域22'相对应,远侧区域104与远侧区域24'相对应,一个或多个开口106与一个或多个开口26'相对应,并且一个或多个开口108与一个或多个开口28'相对应。护套100与护套20'的不同之处在于护套100在远侧区域104附近具有分级部分110。如图10所示,分级部分110可定位在靠近一个或多个开口108的预定距离处,例如1-4cm,使得当分级部分110设置在房间隔的穿刺中时,护套100的远侧区域104不会在左心房内延伸太远。
此外,一个或多个金属线圈,例如,金属线圈112、114和116,可沿与预定的房间分流管尺寸相对应的分级部分110在预选位置处设置在护套100的分级部分110的外表面上。例如,分级部分110处的护套100的横截面积可在从远侧区域104朝向近侧区域102的方向上减小,并且金属线圈112可定位在与例如直径为5mm的房间分流管相对应的分级部分110上,金属线圈114可定位在与例如直径为5.5mm的房间分流管相对应的分级部分110上,并且金属线圈116可定位在与例如直径为6mm的房间分流管相对应的分级部分110上。
因此,在医生使用本文所描述的系统和方法确定哪种尺寸的分流管最适合患者后,可通过房间隔的穿刺向远侧移动护套100,直到房间隔在金属线圈112、114或116中的任何一个内对齐。因此,房间隔的穿刺符合位于其中的分级部分110的横截面积,并且相应的金属线圈可被致动以发射RF能量以消融与金属线圈相邻的组织,以诱导具有与分级部分110的横截面积相对应的尺寸的房间分流管。例如,如果房间隔与金属线圈112对齐,则经由金属线圈112消融的金属线圈112周围的房间组织将导致尺寸适于容纳图7H的房间分流管70的穿刺。类似地,如果房间隔与金属线圈114对齐,则经由金属线圈114消融的金属线圈114周围的房间组织将导致尺寸适于容纳图7H中的房间分流管80的穿刺,并且如果房间隔与金属线圈116对齐,则经由金属线圈116消融的金属线圈116周围的房间组织将导致尺寸适于容纳图7H的房间分流管90的穿刺。如本领域普通技术人员将理解的,沿分级部分110的长度设置的金属线圈可少于或多于三个,和/或分级部分110可具有这样的几何形状,使得设置在其上的金属线圈诱导尺寸小于5mm或大于6mm(例如,6.5mm、7mm、7.5mm,8mm等)的房间分流管。此外,本文所描述的任何护套,例如护套20、护套20'、护套20”、护套20”'或护套20””可包括类似于分级部分110的分级部分。
在一个实施例中,代替分级部分110,护套可具有设置在其上的热球囊,该热球囊靠近被配置为设置在患者左心房中的一个或多个开口,使得在医生使用本文所描述的系统和方法确定哪个尺寸的分流管最适合患者之后,护套100可通过房间隔的穿刺向远侧移动,直到房间隔与热球囊上的金属线圈对齐。然后,可将热球囊充气至选定尺寸,从而将房间隔穿刺扩大至与所需分流尺寸相对应的尺寸。然后可启动热球囊以消融热球囊周围的房间隔组织以诱导所需的房间分流管,从而可将所需的房间分流管植入消融穿刺内。
根据本发明的另一方面,护套可包括两组一个或多个开口,例如,第一组一个或多个开口位于护套的远侧区域,使得它们位于患者的左心房内,以及第二组一个或多个开口,该第二组一个或多个开口定位在护套上与第一组一个或多个开口间隔开的位置处,使得在手术期间当第一组一个或多个开口设置在左心房内时,第二组一个或多个开口位于患者肾静脉尾部的下腔静脉内。因此,根据上述本发明的原理,具有相应的第一和第二组一个或多个孔的内套管可被致动,以改变护套的第二组一个或多个开口的开口面积,以允许血液响应于下腔静脉和左心房之间的压力梯度而在下腔静脉和左心房之间流动。例如,当护套旨在提供从右到左的流量时,如在PAH中,与穿过RA和LA之间护套的较短流动路径相比,流量会减少,这可能在系统校准期间考虑在内。
尽管上文描述了本发明的各种说明性实施例,但是对于本领域技术人员来说,在不脱离本发明的情况下,可进行各种变更和修改是显而易见的。还应了解,本文所描述的装置可植入心脏中的其他位置。例如,装置10可类似地用于治疗远侧腔室(LA)压力高于近侧腔室(RA)压力的情况,如充血性心力衰竭患者中发生的情况。在这种情况下,气流将从左心房流向右心房。正向流和反向流之间的校准有效流直径存在微小差异(例如,约10%),这可通过在致动器上提供单独的校准来实现。此外,根据左心室和右心室之间的压力梯度,装置10可按适合于在左心室和右心室之间分流血液的方向穿过室间隔植入。所附权利要求旨在涵盖属于本发明真正精神和范围内的所有这类变更和修改。
Claims (39)
1.一种用于控制穿过患者的房间隔的血流的装置,所述装置包含:
护套,其具有近侧区域、远侧区域和在所述近侧区域和所述远侧区域之间的内腔,所述远侧区域具有第一组一个或多个开口和第二组一个或多个开口,所述第二组一个或多个开口与所述第一组一个或多个开口间隔开的距离大于所述房间隔的厚度,使得所述第一组一个或多个开口被配置为设置在所述患者的第一心房内,而所述第二组一个或多个开口设置在所述患者的第二心房中;
致动器,其被配置为被致动以修改所述护套的所述第二组一个或多个开口的开口面积,使得允许血液响应于穿过所述房间隔的压力梯度,以与所述护套的所述第二组一个或多个开口的所述开口面积相对应的血流速率,经由所述第一组和第二组一个或多个开口以及其间的所述护套的内腔而在所述第一心房和所述第二心房之间流动。
2.根据权利要求1所述的装置,其中所述护套的所述第二组一个或多个开口包含圆形、椭圆形或细长槽形状中的至少一个,或其任何组合。
3.根据权利要求1所述的装置,其中所述护套的所述第二组一个或多个开口围绕所述护套的外表面对称分布。
4.根据权利要求1所述的装置,其中所述护套的所述第二组一个或多个开口围绕所述护套的外表面不对称分布。
5.根据权利要求1所述的装置,其还包含:
内套管,其具有近侧区域和远侧区域,所述远侧区域的外径等于所述护套的内径,所述内套管可移动地设置在所述护套的所述内腔内,
其中所述致动器被配置为被致动以通过相对于所述护套移动所述内套管一个增量来修改所述护套的所述第二组一个或多个开口的所述开口面积,使得允许血液响应于穿过所述房间隔的压力梯度,以与所述护套的所述第二组一个或多个开口的所述开口面积相对应的血流速率,经由所述第一组一个或多个开口和所述第二组一个或多个开口以及其间的所述护套的内腔而在所述第一心房和所述第二心房之间流动。
6.根据权利要求5所述的装置,其中所述内套管还包含一个或多个冲洗端口,所述冲洗端口经由所述内套管的一个或多个冲洗内腔与冲洗液源流体连通,所述一个或多个冲洗端口被配置为通过其喷射冲洗流体,以防止血液凝块积聚在所述护套的所述第二组一个或多个开口处。
7.根据权利要求5所述的装置,其中所述内套管包含经设定尺寸和形状以用于容纳导丝的导丝内腔。
8.根据权利要求7所述的装置,其还包含压力传感器导丝,所述压力传感器导丝被配置为设置在所述内套管的所述导丝内腔内,所述压力传感器导丝可操作地联接到外部控制器,并且被配置为测量所述第一心房内的压力,并且将指示所述所测得压力的信号传输到所述外部控制器。
9.根据权利要求1所述的装置,其还包含:
内套管,其具有近侧区域、具有与所述护套的所述第一组一个或多个开口流体连通的第一组一个或多个孔的远侧区域,以及在其间延伸的内腔,所述内套管可移动地设置在所述护套的内腔内,并且包含经设定尺寸和形状以与所述护套的所述第二组一个或多个开口配准的第二组一个或多个孔,
其中所述致动器被配置为被致动以通过相对于所述护套移动所述内套管来修改所述护套的所述第二组一个或多个开口的所述开口面积,从而将所述内套管的所述第二组一个或多个孔与所述护套的所述第二组一个或多个开口配准预定量,使得允许血液响应于穿过所述房间隔的压力梯度,以与所述内套管的所述第二组一个或多个孔和所述护套的所述第二组一个或多个开口之间的预定配准量相对应的血流速率,经由所述第一和第二组一个或多个开口和孔以及其间的所述内套管内腔而在所述第一心房和所述第二心房之间流动。
10.根据权利要求9所述的装置,其中所述护套还包含与所述第二组一个或多个开口间隔开的第三组一个或多个开口,使得所述第三组一个或多个开口被配置为设置在所述患者的下腔静脉内,而所述第一组一个或多个开口设置在所述第一心房内,其中所述内套管还包含第三组一个或多个孔,所述第三组一个或多个孔经设定尺寸和形状以与所述护套的所述第三组一个或多个开口配准,并且其中所述致动器还被配置为被致动以相对于所述护套移动所述内套管,从而将所述内套管的所述第三组一个或多个孔与所述护套的所述第三组一个或多个开口配准预定量,使得允许血液响应于所述下腔静脉和所述第一心房之间的压力梯度,经由所述第一组和第三组一个或多个开口和孔以及其间的所述内套管内腔而在所述下腔静脉和所述第一心房之间流动。
11.根据权利要求10所述的装置,其中当所述第三组一个或多个孔与所述第三组一个或多个开口完全配准时,所述内套管的所述第二组一个或多个孔未与所述护套的所述第二组一个或多个开口配准。
12.根据权利要求1所述的装置,其中所述致动器被配置为被致动以增量地选择所述护套的所述第二组一个或多个开口的所述开口面积,使得在每个增量处所述第一心房和所述第二心房之间的所述血流的所述血流速率与通过植入所述患者的房间隔内的预定尺寸的房间分流管的血流的血流速率相对应。
13.根据权利要求12所述的装置,其中所述护套的所述第二组一个或多个开口的所述开口面积与通过直径在4到8mm之间的预定尺寸的房间分流管的血流的血流速率相对应。
14.根据权利要求1所述的装置,其还包含一个或多个传感器,所述一个或多个传感器设置在所述护套的内腔内并可操作地联接到外部控制器,所述一个或多个传感器被配置为测量一个或多个生理参数,并且将指示所述所测得生理参数的信号传输到所述外部控制器。
15.根据权利要求14所述的装置,其中所述一个或多个生理参数包含压力、血流速率、血流速度或血氧含量中的至少一个。
16.根据权利要求1所述的装置,其还包含设置在所述护套的所述远侧区域处的锚固件,所述锚固件被配置为便于将所述护套固定到所述患者的房间隔。
17.根据权利要求16所述的装置,其中所述锚固件包含球囊,所述球囊被配置为防止所述护套相对于所述患者的房间隔移动。
18.根据权利要求17所述的装置,其中所述球囊被配置为在所述第一心房内充气,从而防止所述护套相对于所述患者的房间隔的近侧移动。
19.根据权利要求18所述的装置,其还包含被配置为在所述第二心房内充气的第二球囊,其中所述第一球囊和所述第二球囊在充气时夹住所述房间隔。
20.根据权利要求17所述的装置,其中所述球囊被配置为在所述第二心房内充气,从而防止所述护套相对于所述患者的房间隔向远侧移动。
21.根据权利要求17所述的装置,其中所述球囊包含设置在其外表面上的金属线圈,所述金属线圈被配置为发射足以消融邻近所述金属线圈的组织的射频能量。
22.根据权利要求16所述的装置,其中所述锚固件包含展开尖齿。
23.根据权利要求1所述的装置,其还包含设置在所述护套的外表面上的金属线圈,所述金属线圈被配置为发射足以消融邻近所述金属线圈的组织的射频能量,以诱导房间分流管。
24.根据权利要求23所述的装置,其中所述金属线圈设置在靠近所述第二组一个或多个开口的所述护套的所述外表面上。
25.根据权利要求23所述的装置,其还包含一个或多个附加金属线圈,其中每个金属线圈被配置为发射足以消融邻近所述相应金属线圈的组织的射频能量,以诱导具有预定直径的房间分流管。
26.根据权利要求25所述的装置,其中所述护套的分级部分包含外表面,所述外表面具有在远侧方向上增大的横截面积,所述金属线圈中的每一个沿所述护套的所述分级部分设置在对应于所述预定直径的位置处。
27.一种用于控制穿过患者的房间隔的血流的方法,所述方法包含:
穿过所述患者的房间隔进行穿刺;
穿过所述穿刺递送护套,使得所述护套的第一组一个或多个开口设置在所述患者的第一心房内,而所述护套的第二组一个或多个开口设置在所述患者的第二心房内;
允许血液响应于穿过所述房间隔的压力梯度,经由所述第一组一个或多个开口和所述第二组一个或多个开口以及所述护套的内腔而在所述第一和第二心房之间流动;
修改所述第二组一个或多个开口的开口面积,使得允许血液以修改后的血流速率经由所述第一组一个或多个开口和所述第二组一个或多个开口以及所述护套的内腔而在所述第一心房和所述第二心房之间流动;以及
基于所述允许和所述修改,选择用于植入所述患者的房间隔的房间分流管。
28.根据权利要求27所述的方法,其中致动所述致动器以修改所述第二组一个或多个开口的所述开口面积包含致动所述致动器以将设置在所述护套的内腔内的内套管移动一个增量,使得允许血液以与所述第二组一个或多个开口的所述开口面积相对应的血流速率,经由所述护套的所述第一组一个或多个开口以及设置在所述护套的所述第二组一个或多个开口与所述内套管的所述远侧区域之间的开口而在所述第一和第二心房之间流动。
29.根据权利要求27所述的方法,其中致动所述致动器以修改所述第二组一个或多个开口的所述开口面积包含致动所述致动器以移动设置在所述护套的内腔内的内套管,从而将所述内套管的一个或多个孔与所述护套的所述第二组一个或多个开口配准预定量,使得允许血液响应于穿过所述房间隔的压力梯度,以与所述内套管的所述一个或多个孔与所述护套的所述第二组一个或多个开口之间的所述预定配准量相对应的血流速率,经由所述第一组和第二组一个或多个开口而在所述第一心房和所述第二心房之间流动。
30.根据权利要求27所述的方法,其还包含在穿过所述穿刺递送所述护套后,对设置在所述第一心房内的所述护套的所述远侧区域上的球囊进行充气,从而防止所述护套相对于所述患者的房间隔的近侧移动。
31.根据权利要求27所述的方法,其还包含发射射频能量以消融所述穿刺周围的组织。
32.根据权利要求31所述的方法,其中发射射频能量以消融所述穿刺周围的组织诱导具有预定直径的房间分流管。
33.根据权利要求32所述的方法,其还包含相对于所述房间隔移动所述护套,以将所述房间隔与设置在所述护套的外表面上的金属线圈对齐,并且其中发射射频能量以消融所述穿刺周围的组织包含经由所述金属线圈发射射频能量以消融所述穿刺周围的组织,从而诱导具有所述预定直径的所述房间分流管。
34.根据权利要求27所述的方法,其中所述患者具有肺动脉高压,并且其中所述第一心房是所述患者的左心房,并且所述第二心房是所述患者的右心房,使得允许血液响应于穿过所述房间隔的压力梯度,经由所述护套和所述护套的内腔的所述第一和第二组一个或多个开口而从所述右心房流向所述左心房。
35.根据权利要求27所述的方法,其中所述患者患有心力衰竭,并且其中所述第一心房是所述患者的左心房,并且所述第二心房是所述患者的右心房,使得允许血液能够响应于穿过所述房间隔的压力梯度,经由所述护套和所述护套的内腔的所述第一组和第二组一个或多个开口而从所述左心房流向所述右心房。
36.根据权利要求27所述的方法,其还包含经由设置在所述护套的内腔内的一个或多个传感器来测量所述第一和第二心房之间所述血流的血流速率。
37.根据权利要求27所述的方法,其中所述护套的所述第二组一个或多个开口的所述开口面积允许血液以对应于通过植入所述患者的房间隔内的预定尺寸的直径在4至8mm之间的房间分流管的血流的血流速率相对应的血流速率而在所述第一心房和所述第二心房之间流动。
38.根据权利要求37所述的方法,其还包含经由一个或多个传感器测量所述患者的至少一个生理参数,所述一个或多个传感器在所述第二组一个或多个开口的所述开口的每个增量面积处联接到所述护套,并且将指示所述所测得生理参数的信号传输到操作地联接到所述一个或多个传感器的外部控制器。
39.根据权利要求38所述的方法,其中选择用于植入所述患者的房间隔的所述房间分流管包含基于指示所述所测得生理参数的所述信号选择在其颈部区域处具有预选直径的房间分流管。
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EP3972499A1 (en) | 2022-03-30 |
WO2020234751A1 (en) | 2020-11-26 |
US20200368505A1 (en) | 2020-11-26 |
CN114096205B (zh) | 2024-05-24 |
US11865282B2 (en) | 2024-01-09 |
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