Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
  • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
  • A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
  • A61M1/3621—Extra-corporeal blood circuits
  • A61M1/3653—Interfaces between patient blood circulation and extra-corporal blood circuit
  • A61M1/3659—Cannulae pertaining to extracorporeal circulation

Definitions

• VA-ECMO venous-arterial extracorporeal membrane oxygenation
• AMI Acute myocardial infarction
• VA-ECMO venous-arterial extracorporeal membrane oxygenation
• VA-ECMO drains blood from the venous system, oxygenates this blood outside of the patient, and then delivers oxygenated blood back to the arterial system, e.g., via the femoral artery.
• VA-ECMO is most commonly performed via large-bore cannulas placed in the femoral vein and femoral artery (known as peripheral VA-ECMO).
• VA-ECMO is an established strategy for cardiopulmonary support.
• Largc-borc ECMO cannulac for use in adult humans generally range in diameter from 15 Fr (5.0 mm) to 25 Fr (8.3 mm) and are used to deliver life-sustaining blood flow rates of between 3 and 8 liter/min.
• VA-ECMO peripherally cannulated VA- ECMO may cause kidney injury, increase the risk of stroke, and promote cerebral ischemia, bleeding, and vascular injury. Further, more than one large -bore cannula may be required to achieve high flow rates needed for systemic perfusion with VA-ECMO. Cannula number and size are directly associated with increased risk of bleeding, vascular trauma, and acute limb ischemia.
• peripherally cannulated VA-ECMO may pressurize the entire aorta and increase pressure inside the heart, which increases ventricular wall stress and myocardial oxygen consumption, thereby expanding myocardial damage or infarct size in the setting of a heart attack and increasing fluid in the lungs thereby causing acute lung injury.
• VA-ECMO may cause damage to mitochondria located within the heart, which may limit myocardial recovery.
• concomitant devices such as intra-aortic balloon pumps and Impella® pumps (made available by Abiomed, Danvers, Massachusetts) may be used concomitantly with VA-ECMO and require additional vascular puncture. All of these complications arc associated with increased mortality, long-term morbidity, length of stay in the hospital, and healthcare costs. New approaches to limit complications associated with VA- ECMO are required.
• VA-ECMO support may decrease kidney function and even cause acute kidney injury due to increased arterial pressure and loss of pulsatile flow to the kidney resulting from the high rates of blood flow localized to the outlet region of arterial outlet return cannulas with conventional VA-ECMO. Such injuries may in turn activate autoregulatory mechanisms of the kidneys.
• high rates of non-pulsatile flow encountered with conventional VA-ECMO cannulas have been observed to increase vascular resistance, which in turn increases the workload of the kidneys and exacerbates oxygen consumption.
• Up to 70% of patients receiving VA-ECMO develop acute kidney injury, which is directly associated with mortality.
• VA-E may lead to a significant increase in arterial flow, as well as promote an increase in pressure within the organ itself, which in turn decreases flow in the renal vein.
• the net effect of VA-ECMO use is an increase in pressure inside the organ, such that flow through the kidney is decreased.
• VA-ECMO use results in increased risk of stroke, e.g., acute ischemic stroke and hemorrhagic stroke.
• VA-ECMO induces retrograde blood flow in the femoral artery towards the aorta
• the brain is the last major organ to receive oxygenated blood delivered via a conventional femoral artery cannula.
• differential hypoxia may occur as a result of VA-ECMO patients’ dependence on retrograde flow to deliver oxygenated blood to the upper body.
• physicians currently perform additional vascular punctures in the arteries or veins to place additional large-bore cannulas that increase the risk of complications.
• placement of rigid cannulas from the peripheral artery into a central location in the thoracic aorta may be limited by the inability to navigate large bore cannulas through the iliofemoral bifurcation, tortuous aortas, or across calcified aortas with atheromatous material lining the aorta.
• U.S. Patent No. 8,996,095 to Anderson describes a coronary guide extension catheter having a push member and a distal tubular member, which is configured to be positioned in a coronary artery for use during percutaneous transluminal coronary angioplasty.
• the guide extension catheter described in that patent is designed to stabilize the distal end of a coronary guide catheter to prevent movement away from the patient’s ostium due to beating of the heart during the interventional procedure.
• U.S. Patent No. 10,485,956 to O’Donovan describes a guide extension catheter having a groove in a push member and a distal shaft for guiding an interventional coronary device therethrough.
• coronary guide extension catheters are unsuitable for use as perfusion cannulas in VA-ECMO due to the small lumen diameters and resulting low blood flow rates that could be achieved.
• Guide extension catheters typically have a fixed diameter of between 6 Fr (2 mm) and 8 Fr (2.7 mm). These coronary guide extension catheters are not meant to redirect blood flow, but rather to facilitate delivery of coronary equipment into distal portions of the coronary vasculature.
• U.S. Patent No. 6,632,236 to Hogendijk describes a self-expanding catheter for use in stent delivery, in which a catheter is transluminally inserted in a collapsed delivery state, and self-expands to an expanded deployed state upon removal of a delivery sheath.
• That patent describes a self-expanding anchor formed of a self-expanding wire weave having an elastomeric polymeric coating, and is configured to protect against embolization during vascular interventions.
• the concept described in Hogendijk is not meant to redirect blood flow, but rather to filter out elements in the blood stream.
• VA-ECMO is also used to support commonly performed life-saving procedures such as coronary angioplasty, aortic valvuloplasty, or aortic valve replacement.
• a major limitation of these approaches is the need for additional vascular access to place vascular sheaths and/or catheters for required interventional equipment in addition to the existing VA-ECMO circuit. This can be prohibitive for patients who have peripheral vascular disease, concomitant vascular injury, or vessels occupied by other life-saving equipment. Further, under emergent conditions, placing additional vascular access can be challenging and increase risk of injury.
• U.S. Patent Nos. 5,125,903, 5,195,980, 5,269,764, 7,938,809 describe percutaneous catheter introducers/connectors having hemostatic valves for permitting passage of elongated interventional devices into a patient’s vasculature, and a side port for connection with, e.g., an outside source of perfusion, aspiration, contrast media, medicaments, etc. These systems are not designed for use with VA-ECMO. Moreover, no existing approach allows for simple and effective access to the VA-ECMO circuit for delivery of additional interventional equipment.
• devices and methods arc provided for use with ECMO systems that overcome the disadvantages of the previously known ECMO reperfusion catheters.
• devices constructed in accordance with the present invention enhance blood flow to the thoracic aorta, improve cerebral oxygenation, maintain systemic arterial pulsatility, and reduce the potential for end-organ injury.
• an extension cannula for use with an ECMO return cannula that defines a blood flow path.
• the extension cannula may include the ECMO return cannula, an elongated shaft, e.g., a hypotube, and a flexible socklike conduit coupled to the distal region of the elongated shaft.
• the flexible conduit may be formed of a biocompatible fabric, e.g., at least one of polyethylene, polyurethane, or nylon, and the distal region of the flexible conduit may include a plurality of pores to permit blood flow to exit therethrough.
• a distal portion of the flexible conduit may comprise a tapered portion having a cross-sectional area that decreases towards the distal end of the flexible conduit, such that the outlet of the flexible conduit may include one or more outflow vents disposed on at least the tapered portion of the flexible conduit.
• the one or more outflow vents may be arranged circumferentially around the tapered portion of the flexible conduit, and may extend longitudinally along the tapered portion. For example, a width of the one or more outflow vents may increase in a proximal direction.
• the proximal end of the flexible conduit may engage with the outlet of the ECMO return cannula to form a continuation of the blood flow path through the lumen of the ECMO return cannula, such that the flexible conduit may transition between a collapsed insertion state and an expanded deployed state when in communication with a blood flow from the ECMO machine through the internal lumen of the flexible conduit.
• the proximal end of the flexible conduit may be incorporated into the conventional ECMO return cannula as a single built unit, such that the extension cannula including the flexible conduit and the ECMO return cannula may be advanced into the patient as a single unit, without the need for an existing ECMO return cannula disposed in the patient.
• the proximal end of the flexible conduit may be removably coupled to a conventional ECMO return cannula, e.g., via an expandable anchor as described in further detail below, such that the flexible conduit may be advanced through an ECMO return cannula disposed in the patient in a collapsed delivery state, and expanded within the patient.
• the extension cannula further may include a connection structure, e.g., one or more umbrella-like struts, that couples the flexible conduit to the distal region of the elongated shaft.
• the elongated shaft may be used to advance the flexible conduit to locate the distal end beyond the patient’s renal vessels, and the flexible conduit may have a length selected so that when the extension cannula is in the expanded deployed state, the proximal end is located within the outlet of the ECMO return cannula at a location proximal of the patient’s renal vessels, and the distal end extends beyond the outlet of the ECMO return cannula and the patient’s renal vessels.
• the elongated shaft may have a length selected so that the elongated shaft extends proximally from the tip through the internal lumen of the flexible conduit and beyond the proximal end of the flexible conduit.
• the elongated shaft may extend from the distal end of the flexible conduit proximally along a lateral side of the flexible conduit, or the elongated shaft may extend from the distal end of the flexible conduit proximally within the lumen along a longitudinal axis of the flexible conduit.
• at least a portion of the elongated shaft may be embedded within a membrane of the flexible conduit, such that the at least a portion of the elongated shaft may extend from the distal end of the flexible conduit proximally within the flexible conduit.
• the tip may have one or more holes extending therethrough, the one or more holes sized and shaped to permit blood flow therethrough to mitigate formation of clots adjacent to the tip within the flexible conduit.
• the lumen of the elongated shaft may be sized and shaped to receive a guidewire therethrough.
• the elongated shaft may be configured so that the blood flow path does not pass through the elongated shaft.
• the extension cannula may include an in-line connector coupled between the ECMO machine and the ECMO return cannula, and the in-line connector may include a side arm with a lumen in fluid communication with the lumen of the elongated shaft. Accordingly, the extension cannula may be advanced over a guidewire to the target location within the patient’s vasculature by advancing the elongated shaft over the guidewire until the proximal end of the guidewire extends out of the side arm.
• the in-line connector may be removably coupled to the conventional ECMO return cannula, or it may be incorporated into the conventional ECMO return cannula as a single unit.
• a stylet may be inserted into the lumens of the side arm of the in-line connector and the elongated shaft to prevent blood flow therethrough during operation of the ECMO machine.
• a cap may be configured to removably engage the side arm of the in-line connector to prevent blood flow through the lumen of the elongated shaft during operation of the ECMO machine.
• the proximal end of the flexible conduit may engage with the outlet of the ECMO return cannula by an anchoring stent.
• the anchoring stent may be self-expandable.
• a sheath may be removably disposed over the flexible conduit to retain the flexible conduit in the collapsed insertion state, such that upon retraction of the sheath, the flexible conduit is exposed within the patient’s vasculature.
• the proximal region of the flexible conduit may be fixedly coupled to the ECMO return cannula within the outlet of the ECMO return cannula.
• the proximal region of the flexible conduit may be configured to be fixedly coupled to the ECMO return cannula via at least one of heat sealing, 2- part polyurethane adhesive, or segmented polyurethane bonding.
• the extension cannula further may include an in-line connector separate from the ECMO return cannula.
• the in-line connector may have a first branch sized and shaped to be removably coupled to an outlet of an ECMO circuit, a second branch having a lumen sized and shaped to permit insertion of the extension cannula therethrough, and an outlet sized and shaped to be removably coupled to the ECMO return cannula, such that the first and second branches are in fluid communication with the outlet of the in-line connector.
• the second branch may be co-linear with the outlet of the in-line connector.
• the in-line connector may be removably coupled to the conventional ECMO return cannula, or it may be incorporated into the conventional ECMO return cannula as a single unit.
• a cannula for use with an ECMO machine may include a proximal region having an inlet sized and shaped to be coupled to an ECMO machine, and an outlet sized and shaped to be disposed at a location within a patient’s vasculature proximal of a patient’s renal vessels.
• the cannula may include a conduit formed by a flexible and collapsible tube having a proximal end, a distal end, a length extending therebetween, and a lumen in an expanded deployed state.
• the conduit may transition from a collapsed insertion state to the expanded deployed state when in communication with a blood flow from the ECMO machine.
• the cannula further may include an elongated shaft having a distal region coupled to the distal end of the conduit, such that the elongated shaft may be used to advance the conduit in the collapsed insertion state to locate the distal end beyond the patient’s renal vessels.
• the length of the conduit may be selected so that when the proximal end is located within the outlet at the location within the patient’s vasculature proximal of the patient’s renal vessels, the distal end extends beyond the patient’s renal vessels, and the conduit transitions to the expanded deployed state in the presence of blood flow from the ECMO machine so that the lumen forms a continuation of a blood flow path through the cannula.
• the flexible conduit may include a distal region having a multiplicity of pores sized and shaped to permit the blood flow to exit the lumen.
• the proximal end of the conduit may be affixed to the outlet by a stent.
• an extension cannula for use with a conventional ECMO return cannula.
• the extension cannula includes an elongated shaft having a proximal end and a distal region, and a conduit coupled to the distal region of the elongated shaft.
• the elongated shaft may be used to position a proximal end in fluid communication with the lumen of the conventional ECMO return cannula, so that a distal end of conduit extends beyond the renal arteries, e.g., within the thoracic or abdominal aorta.
• the shaft may include a proximal end that extends through a port near a proximal end of the ECMO return cannula, where it may be manipulated by the clinician.
• the conduit has an inlet, an outlet, an internal lumen extending therebetween, and a diameter configured to transition between a collapsed insertion state and an expanded deployed state.
• the internal diameter of the conduit may be sized and shaped to receive at least one of a catheter for coronary, peripheral vascular, cerebral intervention, or valve intervention, a catheter for antegrade limb perfusion, or a catheter for delivery of intra-aortic, trans-valvular pneumatic, or rotary flow pumps.
• the conduit has a length selected so that when the extension cannula is inserted through a lumen of the conventional ECMO return cannula, the inlet of the conduit is in fluid communication with the outlet of the conventional ECMO return cannula and the outlet of the conduit extends beyond the renal arteries, and may reside in a patient’s thoracic aorta, e.g., the descending aorta, the aortic arch, or the ascending aorta.
• thoracic aorta e.g., the descending aorta, the aortic arch, or the ascending aorta.
• the patient’s thoracic aorta may include the portion of the descending aorta above the level of the diaphragm such that the outlet of the conduit may reside in the descending aorta approaching the level of the diaphragm from beneath the patient’ s thoracic cavity.
• the conduit may include a support structure, such as a self-expanding mesh, weave or braid, encapsulated with a flexible biocompatible coating, e.g., ePTFE.
• the support structure may include a shapememory alloy, plastic or stainless steel spine or skeleton.
• the conduit may be take the form of a hollow sock-like structure having one or more pores coupled to a flexible spine or hypotube.
• the plurality of pores may be disposed in a lateral surface of the conduit.
• the sock-like structure expands when filled with blood being ejected from the ECMO circuit.
• the conduit may be formed of a soft, flexible material such that it may transition to the deployed state by blood pumped by the ECMO system through the internal lumen. The plurality of pores of the soft, flexible material allows blood to exit the lumen without jetting.
• the extension cannula of present invention is expected to provide improved delivery of oxygenated blood from the ECMO machine.
• the conduit may have a length selected, e.g., 20-80 cm, so that when the extension cannula is inserted through the lumen of the ECMO return cannula and transitioned to the expanded deployed state, e.g., in the presence of blood flow from the ECMO machine, the inlet of the conduit may be in fluid communication with the outlet of the ECMO return cannula, the outlet of the conduit may extend beyond the patient’s renal vessels, e.g., into the aortic arch, and the internal lumen may form a continuation of the blood flow path through the internal lumen to deliver blood flow from the ECMO machine beyond the patient’s renal vessels, e.g., to the patient’s aortic arch, to thereby reduce cardiac workload of the patient’s right and left ventricles.
• the reduction of cardiac workload may reduce left ventricular injury and reduce long-term effects
• the single built ECMO cannula may be configured to be positioned through a femoral vein, with the inlet of the extension cannula disposed within a patient’s pulmonary artery, thereby serving as a cannula that selectively enables blood to be withdrawn from the pulmonary artery into the ECMO circuit.
• the outlet of the single built extension cannula may be disposed in a patient’s aortic root or left ventricle, and may be dimensioned to receive at least one of a catheter for coronary, peripheral, cerebral vascular or valvular interventions, or for placement of additional pump technologies within the left ventricle, such as a pneumatic or rotary flow pump inside the aorta, e.g., an intra-aortic balloon pump (lABPs), or trans-valvular rotary flow pump, e.g., Impella® pumps (made available by AbioMed, Danvers, Massachusetts).
• a pneumatic or rotary flow pump inside the aorta e.g., an intra-aortic balloon pump (lABPs), or trans-valvular rotary flow pump, e.g., Impella® pumps (made available by AbioMed, Danvers, Massachusetts).
• a single built extension cannula for use with an ECMO inlet cannula having an inlet and an outlet.
• the extension cannula includes an elongated shaft having a proximal end and a distal region, and an expandable conduit coupled to the distal region of the elongated shaft.
• the conduit has an inlet, an outlet and an internal lumen, and has a diameter that transitions between a collapsed insertion state and an expanded deployed state.
• the conduit has a length selected so that when the extension cannula is inserted through a lumen of the ECMO inlet cannula, the outlet of the conduit is in fluid communication with the outlet of the ECMO inlet cannula and the inlet of the conduit resides in a patient’ s right ventricle.
• the integrally formed cannula and conduit may have a length between 80 to 100 cm, and the conduit may have a length between 40 to 70 cm.
• the extension cannula of the present invention may be used for reducing or preventing myocardial damage in a subject caused by acute myocardial infarction, heart failure, cardiac arrest, pulmonary embolism, myocarditis, or lung injury, e.g., by reducing left heart workload and improving function of mitochondrial CI.
• the extension cannula of the present invention may be used for reducing myocardial infarct size due to an obstruction of coronary blood flow and limiting the development of post-infarction heart failure.
• the extension cannula of the present invention may be used for increasing cardio-protective signaling pathways in the heart during acute myocardial infarction or heart failure to reduce myocardial injury and improve myocardial recovery, ameliorating the effects of compromised lung function and reducing the occurrence and severity of north- south syndrome, and enhancing antegrade blood flow to the patient’s descending aorta and adjoining arteries, thereby unloading the patient’s left ventricle, reducing cardiac output at a lower pressure, and decreasing left and right ventricular workload.
• kits for use with an ECMO machine may include a cannula comprising a proximal region having an inlet configured to be coupled to the ECMO machine, and an outlet configured to be disposed at a location within a patient’s vasculature proximal of a patient’s renal vessels, and an extension cannula.
• the extension cannula may include a flexible conduit having a proximal end, a distal end, a length extending therebetween, and a lumen in an expanded deployed state.
• the flexible conduit may transition from a collapsed insertion state to the expanded deployed state when in communication with a blood flow from the ECMO machine so that the lumen forms a continuation of a blood flow path through the cannula.
• the extension cannula further may include an elongated shaft having a distal region coupled to the distal end of the flexible conduit. The elongated shaft may be configured to advance the flexible conduit in the collapsed insertion state to locate the distal end beyond the patient’s renal vessels.
• the kit further may include a peel-away introducer disposed on at least a portion of the flexible conduit. The peel-away introducer may be retracted proximally relative to the flexible conduit and peeled off of the flexible conduit.
• the length of the flexible conduit may be selected so that when the proximal end is located within the outlet at the location within the patient’ s vasculature proximal of the patient’s renal vessels, the distal end extends beyond the patient’s renal vessels.
• the peel-away introducer may have a diameter that is at most equal to a diameter of the cannula. In some embodiments, the peel-away introducer may extend along an entire length of the flexible conduit.
• the elongated shaft may extend from the distal end of the flexible conduit proximally along a lateral side of the flexible conduit. For example, the elongated shaft may extend along the inner surface of the flexible conduit, along the outer surface of the flexible conduit, or may be embedded within the membrane of the flexible conduit. Alternatively, the elongated shaft may extend from the distal end of the flexible conduit proximally within the lumen along a longitudinal axis of the flexible conduit. For example, the elongated shaft may extend along a center portion of the lumen.
• the elongated shaft may be embedded within a membrane of the flexible conduit, such that the at least a portion of the elongated shaft may extend from the distal end of the flexible conduit proximally within the flexible conduit.
• the elongated shaft may be configured so that the blood flow path does not pass through the elongated shaft.
• the elongated shaft may contain a hypotube which provides a lumen configured to receive a guidewire therethrough.
• the extension cannula further may include a support coupled to a distal region of the flexible conduit.
• the support may extend circumferentially along the flexible conduit and may transition from a collapsed delivery state to an expanded deployed state.
• the extension cannula may include a plurality of connection structures extending between the distal end of the flexible conduit and the support. The plurality of connection structures may transition from a collapsed delivery state to an expanded deployed state.
• a distal end of the elongated shaft may include an atraumatic tip configured to be coupled to the support via the plurality of connection structures.
• the atraumatic tip may comprise one or more holes extending therethrough, the one or more holes sized and shaped to permit blood flow therethrough to mitigate formation of clots adjacent to the tip within the flexible conduit.
• the flexible conduit may include at least one of polyethylene, polyurethane, or nylon.
• an outlet of the flexible conduit may include one or more pores disposed at a distal region of the flexible conduit.
• a distal portion of the flexible conduit may comprises a tapered portion having a cross-sectional area that decreases towards the distal end of the flexible conduit, such that an outlet of the flexible conduit comprises one or more outflow vents disposed on at least the tapered portion of the flexible conduit.
• the one or more outflow vents may be arranged circumferentially around the tapered portion of the flexible conduit, and may extend longitudinally along the tapered portion.
• a width of the one or more outflow vents may increase in a proximal direction.
• the proximal end of the flexible conduit may be fixedly coupled to the cannula within the outlet of the cannula.
• the proximal end of the flexible conduit may be configured to be fixedly coupled to the cannula via at least one of heat sealing, 2-part polyurethane adhesive, or segmented polyurethane bonding.
• the proximal end of the flexible conduit may be integrally formed with the outlet of the cannula.
• the integrally formed cannula and flexible conduit may have a length between 80 to 100 cm, and the flexible conduit may have a length between 40 to 70 cm.
• the kit further may include one or more sensors disposed at a distal region of the extension cannula.
• the one or more sensors may be configured to measure at least one of pressure, flow, or oxygen saturation within the patient’s vasculature.
• the kit further may include a console operatively coupled to the one or more sensors, the console configured to display measurements of the one or more sensors.
• the elongated shaft may have a lumen sized and shaped to receive one or more electrical wires extending between the one or more sensors and the console.
• a method for improving systemic perfusion may include: advancing a distal end of a flexible extension cannula within a patient’s vasculature via an elongated shaft coupled to the distal end of the flexible extension cannula, a proximal region of the flexible extension cannula coupled to an outlet of an ECMO return cannula in fluid communication with an ECMO machine, at least a portion of the flexible extension cannula disposed within a peel-away introducer; positioning the peel-away introducer into the patient’s vasculature, such that a proximal end of the peel-away introducer remains external to the patient and the distal end of the flexible extension cannula is positioned within the patient’s vasculature; retracting the peel-away introducer relative to the flexible extension cannula and peeling the peel-away introducer off of the flexible extension cannula; advancing the ECMO return cann
• Transitioning the flexible extension cannula from the collapsed insertion state to the expanded deployed state may include transitioning a support extending circumferentially along a distal region of the flexible extension cannula from a collapsed delivery state to an expanded deployed state, and optionally, transitioning a plurality of connection structures extending from the distal end of the flexible extension cannula to the support from a collapsed delivery state to an expanded deployed state.
• FIG. 1A is a side view of an extension cannula for improving reperfusion during ECMO, constructed in accordance with the principles of the present invention, with the extension conduit in an expanded state and with the delivery sheath removed.
• FIG. IB is a side view of the extension cannula of FIG. 1A, with the extension conduit in a contracted state within the delivery sheath.
• FIG. 2 is a side view of an alternative embodiment of the extension cannula of FIG. 1A, with the extension conduit in an expanded state and the delivery sheath removed.
• FIG. 3A is a schematic view of an exemplary in-line connector configured for use with the extension cannulas of the present invention.
• FIG. 3B illustrates an end cap for use with the in-line connector of FIG. 3 A.
• FIGS. 4A-4C are schematic views illustrating use of an exemplary in-line connector with the extension cannula FIG. 1 A in an ECMO system.
• FIG. 4D is a schematic view illustrating use of an exemplary in-line connector with an alternative exemplary extension cannula in an ECMO system.
• FIG. 5 is a flow chart of exemplary steps for improving perfusion during ECMO in accordance with the principles of the present invention.
• FIGS. 6A-6E illustrate the exemplary steps for improving perfusion during ECMO using the extension cannula of FIG. 1 A.
• FIG. 7 A is a side view of an alternative exemplary extension cannula for improving reperfusion during ECMO, constructed in accordance with the principles of the present invention, with the extension conduit in a partially collapsed state.
• FIG. 7B is a side view of extension cannula of FIG. 7A in an expanded state.
• FIGS. 8A-8C are schematic views illustrating use of an exemplary in-line connector with the extension cannula of FIGS. 7A and 7B in an ECMO system.
• FIG. 8D is a schematic view illustrating use of the extension cannula of FIGS. 7A and 7B in an ECMO system.
• FIGS. 9A and 9B illustrate exemplary steps for improving perfusion during ECMO using the extension cannula of FIGS. 7A and 7B and an exemplary in-line connector.
• FIGS. 10A and 10B illustrate exemplary steps for improving perfusion during ECMO using the extension cannula of FIGS. 7A and 7B.
• FIG. 11 A is a schematic view illustrating use of an exemplary in-line connector with an alternative exemplary extension cannula in an ECMO system, constructed in accordance with the principles of the present invention, where a proximal end of the extension cannula is coupled to a conventional ECMO cannula.
• FIG. 1 IB is a schematic view illustrating use of the extension cannula of FIG. 11 A in an ECMO system without an in-line connector.
• FIG. 11C is a schematic view illustrating use of an exemplary connector having a side arm with the extension cannula of FIG. 11 A in an ECMO system.
• FIGS. 1 ID to 1 IF are cross-sectional views of the extension cannula of FIG. 1 IB.
• FIG. 12 is a flow chart of exemplary steps for improving perfusion during ECMO using the extension cannula of FIGS. 11 A to 11C in accordance with the principles of the present invention.
• FIGS. 13 A and 13B illustrate exemplary steps for improving perfusion during ECMO using the extension cannula of FIG. 11A.
• FIGS. 14A and 14B illustrate exemplary steps for improving perfusion during ECMO using the extension cannula of FIG. 1 IB.
• FIGS. 15A and 15B illustrate exemplary steps for improving perfusion during ECMO using the extension cannula of FIG. 11C.
• FIG. 16 illustrates an alternative exemplary extension cannula in an ECMO system having one or more sensors, constructed in accordance with the principles of the present invention, where a proximal end of the extension cannula is coupled to a conventional ECMO cannula.
• FIGS. 17A and 17B are schematic views illustrating the extension cannula of FIG.
• FIG. 17C is a schematic view illustrating the extension cannula of FIG. 11C with a peel away introducer constructed in accordance with the principles of the present invention.
• FIG. 20C is a cross-sectional view of the extension cannula of FIG. 20A.
• FIGS. 21 A and 2 IB illustrate alternative extension cannulas having a central hypotube constructed in accordance with the principles of the present invention.
• FIG. 21C is a cross-sectional view of the extension cannula of FIG. 21A.
• FIG. 22A to 22C illustrate various arrangements of the multiplicity of pores of the extension cannula in accordance with the principles of the present invention.
• FIG. 23A illustrates the distal end of an alternative extension cannula having a lateral hypotube constructed in accordance with the principles of the present invention.
• FIG. 23B illustrates the distal end of an alternative extension cannula having a central hypotube constructed in accordance with the principles of the present invention.
• FIG. 24 is a graph illustrating VA-ECMO stroke risk.
• FIG. 25 depicts north-south syndrome in a patient on ECMO.
• FIG. 26 is a series of graphs illustrating various parameters for standard conventional ECMO cannulation compared to those achieved using alternate cannulation (delivery of blood to the thoracic aorta) in accordance with the principles of the present invention.
• FIG. 27 is a series of graphs illustrating various parameters resulting from use of standaid conventional ECMO cannulation, an Impella pump, and an exemplary system of the present invention.
• FIG. 28 is a series of graphs representing renal arterial blood velocity obtained for standard conventional ECMO cannulation and an exemplary alternate (irrigation) cannulation system of the present invention.
• FIG. 29 are graphs illustrating renal arterial pulsatility and renal arterial microvascular resistance for standard conventional ECMO cannulation and an exemplary alternate cannulation system of the present invention.
• FIG. 30 is a graph showing urinary levels of kidney injury molecules associated with use of standard conventional ECMO cannulation and an exemplary alternate cannulation system of the present invention.
• FIG. 31A illustrates left ventricular and right ventricular response during conventional ECMO cannulation.
• FIG. 3 IB illustrates left ventricular and right ventricular response during ECMO using the extension cannula of the present invention.
• FIG. 32 are graphs illustrating pressure volume area (PVA), stroke work (SW), and end-diastolic pressure (EDP) associated with use of standard conventional ECMO cannulation and an exemplary alternate cannulation system of the present invention.
• PVA pressure volume area
• SW stroke work
• EDP end-diastolic pressure
• FIG. 33A illustrates infarct size associated with use of standard conventional ECMO cannulation and an exemplary alternate cannulation system of the present invention.
• FIG. 33B is a graph show infarct size associated with standard ischemia and reperfusion injury (IRI) and use of standard conventional ECMO cannulation and an exemplary alternate cannulation system of the present invention.
• IRI ischemia and reperfusion injury
• FIG. 34 are graphs illustrating oxygen consumption rate (OCR) associated with standard ischemia and reperfusion injury (IRI) and use of standard conventional ECMO cannulation, with and without an Impella, and an exemplary alternate cannulation system of the present invention.
• OCR oxygen consumption rate
• IRI standard ischemia and reperfusion injury
• FIG. 35 is a graph illustrating oxygen consumption rate (OCR) associated with standard ischemia and reperfusion injury (IRI) and use of standard conventional ECMO cannulation, with and without an Impella, and an exemplary alternate cannulation system of the present invention for mitochondrial complex I (CI) function.
• OCR oxygen consumption rate
• IRI standard ischemia and reperfusion injury
• CI mitochondrial complex I
• FIG. 36A illustrates an extension cannula in an ECMO system constructed in accordance with the principles of the present invention, where a distal end of the extension cannula is disposed within the pulmonary artery and a proximal end of the extension cannula is coupled to a conventional ECMO cannula via the femoral vein.
• FIG. 36B illustrates an extension cannula in an ECMO system constructed in accordance with the principles of the present invention, where a distal end of the extension cannula is disposed within the pulmonary artery and a proximal end of the extension cannula is coupled to a conventional ECMO cannula via the internal jugular vein.
• Systems and methods are provided for use with ECMO systems to enhance blood flow to the thoracic aorta, ascending aorta and aortic arch, thereby facilitating normal antegrade flow to the carotid and other downstream arteries, while reducing high blood flow rates and the potential for reperfusion injury to the kidneys.
• the systems and methods of the present invention also may ameliorate the occurrence of north- south syndrome in patients with impaired lung function, thereby ensuring adequate flow of oxygenated blood to the patient’s cerebral vasculature.
• extension cannula 10 suitable for use with a conventional VA- ECMO cannula is described.
• Extension cannula 10 may be constructed as described in U.S. Patent Nos. 11,331,421 and 11,547,786, the entire contents of each of which are incorporated herein by reference.
• extension cannula 10 may include shaft 17 extending between distal region 11 and proximal region 13 of extension cannula 10.
• Shaft 17 is formed of a material, e.g., stainless steel rod, having sufficient rigidity to permit cannula 10 to be advanced through a conventional ECMO reperfusion cannula so that distal region 11 of self-expanding conduit 12 may be disposed with its outlet extending beyond a patient’s renal arteries, and preferably extending in a patient’s ascending aorta or in the vicinity of the aortic arch.
• Selfexpanding conduit 12 optionally may include handle 15 coupled to shaft 17 at proximal region 13 of self-expanding conduit 12 for maneuvering extension cannula 10.
• Self-expanding conduit 12 has inlet 16 at its proximal end and outlet 14 at its distal end, and a lumen extending therethrough for permitting blood flow.
• Self-expanding conduit 12 has a length sufficient to extend from the outlet the conventional VA-ECMO cannula to a position above the patient’s renal arteries, and more preferably, into the thoracic aorta, e.g., 15- 120 cm or preferably 20-80 cm.
• self-expanding conduit 12 includes a self-expanding support structure, such as a mesh, weave or braid, covered by a flexible and biocompatible covering. Moreover, as shown in FIG.
• self-expanding conduit 12 may include one or more radiopaque markers 18 disposed along the distal end of self-expanding conduit 12 adjacent outlet 14 to permit its location to be determined fluoroscopically.
• the biocompatible covering in the vicinity of the distal end of self-expanding conduit 12 may be omitted to permit blood to exit laterally therethrough and perfuse the thoracic aorta.
• the support structure of self-expanding conduit 12 may be made of a wire mesh, weave or braid formed of a shape-memory metal or stainless steel, such that self-expanding conduit 12 may transition from a collapsed insertion state and an expanded deployed state.
• the support structure of the conduit may be formed of a stainless steel mesh, weave or braid having a preset expanded diameter that forms a central lumen, such that the conduit may be contracted when pulled within smaller diameter delivery sheath 40.
• the support structure may be a mesh, weave or braid formed of a shape-memory metal such as a nickel-titanium alloy (“Nitinol”), and having a predetermined expanded diameter that forms the internal lumen.
• Nitinol nickel-titanium alloy
• the conduit may be contracted to the collapsed insertion state when pulled within delivery sheath 40 as described in further detail below.
• the support structure preferably is encapsulated with a biocompatible polymer coating, such as expanded polytetrafluoroethylene (“ePTFE”).
• ePTFE expanded polytetrafluoroethylene
• self-expanding conduit 12 assumes a diameter substantially the same as, or even larger than, the internal lumen of a conventional VA-ECMO cannula, and thus docs not require a largcr-borc opening in the femoral vasculature.
• the width of self-expanding conduit 12 may range from 14 Fr to 40 Fr in the expanded state.
• self-expanding conduit 12 When inserted through a conventional ECMO cannula, self-expanding conduit 12 permits enhanced blood flow to the ascending aorta and aortic arch, while maintaining the diameter of the vascular opening in the femoral artery required to introduce the conventional VA-ECMO return cannula.
• the biocompatible polymer coating may include pores that permit blood to perfuse laterally through the material, thereby reducing jetting from outlet 14.
• inlet 16 at the proximal end of self-expanding conduit 12 may have a feature for facilitating recapture of self-expanding conduit 12 within the delivery sheath.
• self-expanding conduit 12 may have tapered geometry 19 that facilitates retrieval of self-expanding conduit 12.
• the support structure of self-expanding conduit 12 may include a laterally displaced wire hoop that resides along the edge of inlet 16, thereby forming tapered geometry 19.
• the distal end of shaft 17 may be coupled to support legs coupled to the proximal end of the support structure of self-expanding conduit 12, such that advancing a sheath over the support legs causes the support structure of self-expanding conduit 12 to collapse inwardly to the collapsed insertion state as described in further detail below.
• the distal end of selfexpanding conduit 12 may include an atraumatic region.
• conduit 12' is made of a soft flexible material, such as polyethylene, polyurethane, or nylon, and may include pores that permit some blood to perfuse laterally through the material while directing the bulk of the flow through conduit 12' to outlet 14'.
• Elongated shaft 17' serves as a spine to assist in passing extension conduit 12' through the lumen of a conventional ECMO cannula, and to position inlet 16' near the outlet of the ECMO cannula, and outlet 14' in distal region 11' above a patient’s renal arteries, and more preferably, extending into the patient’s thoracic aorta.
• Shaft 17' may be coupled to handle 15' for maneuvering device 10'.
• Conduit 12' preferably includes at its proximal end a self-expanding support hoop 19' that expands the opening 16' at proximal end of conduit 12' when released from a delivery sheath, as described above with respect to FIG. IB.
• Conduit 12' may include radiopaque markers 18' near outlet 14'.
• Support hoop 19' ensures that blood flowing through the conventional ECMO cannula is funnclcd into the proximal end of conduit 12' and causes the remainder of conduit 12' to fully open.
• conduit 12' may be collapsed at the conclusion of a reperfusion procedure by advancing sheath 40 distally over elongated shaft 17' and conduit 12'.
• in-line connector 20 suitable for use with the extension cannula of the present invention is described.
• In-line connector 20 has first branch inlet 22 configured to be coupled to an outlet of a conventional ECMO machine for receiving oxygenated blood from an ECMO circuit, second branch inlet 26 having a hemostatic valve welded therein, and outlet 24 configured to be coupled to a conventional ECMO cannula.
• First branch inlet 22 and second branch inlet 26 each are in fluid communication with outlet 24, and each may include an optional hemostatic valve 25, as described below with respect to FIG. 3B.
• the fluid pathway extending between first branch inlet 22 and outlet 24 thus permits oxygenated blood received from an ECMO circuit to flow to through the conventional ECMO cannula and self-expanding conduit 12.
• the fluid pathway extending between second branch inlet 26 and outlet 24 is sized and shaped to permit delivery therethrough of self-expanding conduit 12 in a collapsed insertion state, e.g., when disposed within delivery sheath 40.
• extension cannula 10 of FIGS. 1 A and IB or extension cannula 10' of FIG. 2 may be inserted through the hemostatic valve of second branch inlet 26 and advanced through the lumen of the conventional ECMO return cannula coupled to outlet 24.
• the fluid pathway extending between second branch 26 and outlet 24 may be sized and shaped to permit delivery of other interventional tools therethrough as well, including, e.g., a catheter for coronary, peripheral, or cerebral vascular or valvular interventions, and/or a pneumatic, rotary, or transvalvular flow pump. Delivery of extension cannula 10 or 10' and other large-bore interventional devices or small catheters is possible due to co-linearity of second branch inlet 26 with outlet 24. Unlike previously known Y-shaped connectors used in interventional procedures, the linear alignment of second branch inlet 26 and outlet 24 of in-line connector 20 permits a device to be inserted without bending.
• second branch inlet 26 and outlet 24 of in-line connector 20 accommodates delivery of large bore devices, e.g., a delivery catheter for a transcatheter aortic valve replacement (TAVR) valve, an Impella pump, or smaller catheters such as coronary, cerebral, or peripheral vascular interventional guide catheters.
• TAVR transcatheter aortic valve replacement
• Impella pump or smaller catheters such as coronary, cerebral, or peripheral vascular interventional guide catheters.
• In-line connector 20 may be removably coupled to the conventional ECMO return cannula when the extension cannula or other interventional devices are required to be delivered, e.g., by clamping the ECMO return cannula, decoupling the ECMO return cannula from the ECMO circuit, coupling in-line connector 20 to the ECMO circuit and the ECMO return cannula via first branch inlet 22 and outlet 24, respectively, and unclamping the ECMO return cannula.
• in-line connector 20 enables extension of existing short ECMO cannulas, adjustment of location of the extension cannula within the aorta, and removal of the extension cannula without disrupting ECMO flow.
• in-line connector 20 may be integrally constructed as part of the ECMO return cannula, e.g., a 15, 17, 19, 21, or 25 Fr conventional ECMO return cannula.
• in-line connector 20 may include an end cap coupled second branch inlet 26 when no device is delivered therethrough.
• second branch inlet 26 may include a hemostatic valve to prevent backflow of blood during delivery of the extension cannula or other interventional device, and the end cap may be coupled to second branch inlet 26 to prevent further exposure of the hemostatic valve.
• the single built cannula enables rapid delivery of flow above the renal vessels without the need for an inline connector and also enables positioning of the extension cannula along the length of the aorta.
• the single built cannulas described herein may have a length sufficient to extend from the outlet of the VA-ECMO circuit to a position above the patient’s renal arteries, and more preferably, into the thoracic aorta.
• the single built cannula may have an overall length between 80-100 cm, e.g., from the proximal end of the single built cannula to the distal tip of the expandable conduit.
• the single built cannula may have a length between 60-80 cm from the outlet of the ECMO return cannula to the distal tip of the expandable conduit, and the expandable conduit may have a length between 40-70 cm.
• side arm 27 coupled to, and in fluid communication with, second branch inlet 26.
• Side arm 27 may be used for flushing of in-line connector 20 or may be used to fluidly couple in-line connector 20 to an antegrade perfusion catheter to perfuse the patient’s lower extremities to protect against limb ischemia.
• an antegrade perfusion catheter may be inserted via side arm 27, through in-line connector 20 and the convention ECMO return cannula, and positioned within the patient such that oxygenated blood is delivered to the patient’s lower extremities.
• hemostatic valve 25 may have a diameter, e.g., a 3/8 inch, sized for selectively closing off second branch inlet 26 when not in use.
• an end cap may include a double hemostatic valve, as depicted in FIG. 3B, for preventing backflow of blood through second branch inlet 26 of in-line connector 20 when extension catheter is inserted therethrough.
• an end cap may have stopper portion having a length that extends substantially for the length of the lumen of second branch inlet 26, such that it prevents blood from pooling in the lumen of second branch inlet 26.
• end cap 34 includes adapter portion 35 that may be inserted into the outlet tubing of a conventional ECMO system.
• End cap 34 preferably includes internal lumen 36 having a diameter smaller than the lumen of second branch inlet 26, and suitable for, e.g., drug infusion or pressure/flow monitoring.
• end cap 34 may include a hemostatic valve positioned within lumen 36 to prevent backflow of blood therethrough.
• end cap 34 may include, e.g., a screw (aperture) valve, a balloon valve, a double membrane valve, etc.
• lumen 36 may have a diameter selected depending on which procedure is desired.
• End cap 34 may be coupled to a second arm of in-line connector 20 described above to permit delivery of interventional tools and/or removal of an existing ECMO cannula therethrough as described above.
• End cap 34 may be, e.g., a screw cap, that may be rotatably coupled to the in-line connector and/or existing ECMO cannula.
• end cap 34 may be incorporated directly into an existing ECMO cannula.
• end cap 34 may be coupled to the existing ECMO cannula directly, e.g., either as two separate components coupled together or an integral component, such that the existing ECMO cannula is in fluid communication with the ECMO circuit via end cap 34.
• end cap 34 may include one or more hemostatic valves to prevent backflow of blood therethrough.
• an existing ECMO cannula needs to be removed and/or replaced, e.g., to exchange an existing ECMO cannula for a larger diameter ECMO cannula, the existing ECMO cannula may be removed through the lumen of end cap 34.
• a clamp may be applied to the ECMO circuit so that the ECMO circuit may be decoupled from end cap 34.
• a guidewire then may be introduced through the lumen of end cap 34.
• the existing ECMO cannula may be removed over the guidewire, and a new, larger ECMO cannula, e.g., a 19 Fr cannula, may be advanced over the guidewire through the lumen of end cap 34, and positioned within the patient’s vasculature.
• the ECMO circuit may then be recoupled to end cap 34 and unclamped to permit blood to once again flow from the ECMO circuit through the new, larger ECMO cannula.
• the ECMO circuit may be decoupled from end cap 34 in the manner described above when interventional tool(s) need to be delivered to the patient, and recoupled when the interventional procedure is complete.
• FIGS. 4 A to 4C operation of the embodiment of the extension cannula of FIGS. 1A and IB is schematically depicted in conjunction with in-line connector 20 of FIG. 3 A.
• conventional ECMO cannula 60 is coupled to outlet 24 of in-line connector 20 and inserted into a patient’s arterial vasculature, e.g., via a cut down to the femoral artery, as shown in FIG. 4A.
• the outlet line from an ECMO machine is coupled to first branch inlet 22.
• FIG. 4A As shown in FIG.
• extension cannula 10 disposed with self-expanding conduit 12 in its collapsed insertion state within delivery sheath 40, is advanced through the hemostatic valve of second branch inlet 26 of in-line connector 20.
• Extension cannula 10 is positioned so that the distal end of self-expanding conduit 12 is disposed in the desired location, e.g., within the thoracic aorta, and the proximal end of self-expanding conduit 12 lies near the distal outlet of the conventional ECMO return catheter, e.g., as may be determined under fluoroscopy using, e.g., radiopaque marker bands disposed on sheath 40.
• the lumen of sheath 40 preferably is dimensioned to accept and retain self-expanding conduit 12 in its collapsed insertion state.
• the lumen of sheath 40 may have a diameter between 1.40 mm and 1.50 mm, and more preferably 1.45 mm.
• Sheath 40 has an outer diameter sized to it to be readily inserted through the lumen of a conventional VA-ECMO return cannula.
• Sheath 40 is slidably disposed over self-expanding conduit 12 so that it may be retracted relative to self-expanding conduit 12, thereby permitting self-expanding conduit 12 to self-expand from the collapsed insertion state to the expanded, deployed state.
• interventional tools e.g., vascular catheters, valve catheters, or intra-aortic or trans-valvular pumps, e.g., Impella® pump (made available by Abiomed, Danvers, Massachusetts)
• Impella® pump made available by Abiomed, Danvers, Massachusetts
• arterial repair tools may delivered to the patient’s vasculature through the inline connector to facilitate removal of, e.g., an arterial cannula.
• the in-line connector may be used to provide wire re-access to the native femoral vessel, thereby allowing for removal of the ECMO cannula and delivery of vascular closure devices at the time of ECMO decannulation, thereby avoiding the need for surgical repair of the vessel.
• self-expanding conduit 12 has a length between 20 to 80 cm or longer. In this manner, blood may be delivered in the vicinity of a patient’s thoracic aorta, above the patient’s renal artery ostia, to avoid high flow rates in the vicinity of the patient’s renal arteries and reduce the risk of perfusion injury.
• self-expanding conduit 12 can provide oxygenated blood to the cardiac arteries in the vicinity of the aortic root and also provide antegrade flow to the carotid arteries and downstream arteries.
• sheath 40 when the patient is to be removed from ECMO, sheath 40 may be re-inserted over elongated shaft 17 and advanced to collapse and retrieve self-expanding conduit 12. In this case, sheath 40 will first engage tapered proximal end 19 of self-expanding conduit 12, such that advancement of sheath 40 while retaining shaft 17 stationary will cause self-expanding conduit 12 to collapse inward and return to its reduced diameter, collapsed insertion state. Extension cannula 10 and sheath 40 may then be removed through the hemostatic valve within second branch inlet 26.
• Use and operation of the embodiment of FIG. 2 is substantially the same as described above.
• Self-expanding conduit 12" may be constructed similar to self-expanding conduit 12 of FIG. 4C.
• self-expanding conduit 12" has inlet 16", outlet 14", and one or more radiopaque marker bands 18", which correspond with inlet 16, outlet 14, and bands 18 of self-expanding conduit 12, respectively.
• Self-expanding conduit 12" differs from self-expanding conduit 12 in that, instead of tapered inlet geometry 19, self-expanding conduit 12" has plurality of angled legs 41 that couple self-expanding conduit 12" to elongated shaft 17" to facilitate resheathing for removal.
• angled legs 41 are flexible and of uniform length, so that when the distal end of sheath 40 is advanced over angled legs 41, the legs flex inward to cause the support structure of self-expanding conduit 12" to collapse inward.
• sheath 40 may have a rapid exchange configuration, with sheath 40 having a length suitable for covering the entire length of self-expanding conduit 12, 12" but is joined to a support shaft and a handle coupled to the end of the support shaft. In this manner, sheath 40 may be back-loaded over the proximal end of elongated shaft 17, 17" of the extension cannula and manipulated using the support shaft via the handle, without interfering with the ability to manipulate the proximal end of shaft 17, 17".
• FIG. 4D operation for the alternative embodiment of the extension cannula is similar to that of the embodiment of FIGS. 4A to 4C.
• selfexpanding conduit 12" and sheath 40 are advanced through in-line connector 20 (see FIG. 4B) and into the lumen of conventional ECMO return cannula 60 with self-expanding conduit 12" in the collapsed insertion state within sheath 40.
• Sheath 40 is withdrawn proximally while selfexpanding conduit 12" is retained stationary using elongated shaft 17", thereby permitting selfexpanding conduit 12" to self-expand to its predetermined diameter, as shown in FIG. 4D.
• FIG. 6A illustrates conventional ECMO cannula 60 inserted through the patient’s femoral artery FA coupled to ECMO machine 61 via outlet 24 and first inlet 22 of in-line connector 20 as described above.
• FIG. 6A illustrates conventional ECMO cannula 60 inserted through the patient’s femoral artery FA coupled to ECMO machine 61 via outlet 24 and first inlet 22 of in-line connector 20 as described above.
• guide wire 62 may be inserted through second branch inlet 26 and outlet 24 of in-line connector 20, and through ECMO cannula 60 until the distal end of guidewire 62 is advanced to the desired location within the patient’s vasculature, e.g., within the thoracic aorta TA such as within the ascending aorta or in the vicinity of the aortic arch.
• the distal end of sheath 40 having self-expanding conduit 12 disposed therein in a collapsed insertion state, is advanced through ECMO cannula 60, e.g., over guidewire 62, via in-line connector 20.
• sheath 40 is advanced until it is positioned at the desired central location within the patient’s vasculature at step 52 as shown in FIG. 6C.
• sheath 40 is retracted relative to self-expanding conduit 12 slidably disposed within the lumen of sheath 40, while self-expanding conduit 12 remains stationary, causing self-expanding conduit 12 to transition from the collapsed insertion state to an expanded deployed state as shown in FIGS. 6D and 6E.
• FIG. 6D illustrates self-expanding conduit 12 partially fully expanded within the patient’s vasculature
• FIG. 6D illustrates self-expanding conduit 12 partially fully expanded within the patient’s vasculature
• FIG. 6E illustrates self-expanding conduit 12 fully expanded within the patient’s vasculature, e.g., when self-expanding conduit 12 is fully exposed from sheath 40.
• oxygenated blood may be perfused from ECMO cannula 60 to the central location within the patient’s vasculature, e.g., within the ascending aorta or in the vicinity of the aortic arch.
• blood flow into the adjacent vessels e.g., the coronary arteries and/or the carotid arteries, will occur and with a more normal antegrade flow pattern.
• the outlet of self-expanding conduit 12 may be positioned within the descending aorta, e.g., the portion of the descending aorta approaching the level of the diaphragm from beneath the thoracic cavity or the portion of the descending aorta above the diaphragm.
• the ECMO pump may be programmed to generate a pulsatile flow to create pressure fluctuations at the outlet of selfexpanding conduit 12 that mimics the patient’s heartbeat.
• the patient may receive significant benefits such as retaining the elasticity of the arteries and reducing arterial stiffening, as opposed to with continuous flow.
• selfexpanding conduit 12 may be returned to the collapsed insertion state within the lumen of sheath 40 as described above, and at step 56, sheath 40 and self-expanding conduit 12 disposed therein may be removed from the patient.
• Extension cannula 70 may be constructed as described in U.S. Patent No. 11,547,786 and U.S. Patent Appl. No. 18/151,982, the entire contents of each of which arc incorporated herein by reference.
• extension cannula 70 may include elongated shaft 77, e.g., a hypotube, extending between distal region 71 and proximal region 73 of extension cannula 70.
• Hypotube 77 is formed of a material, e.g., stainless steel rod, having sufficient rigidity to permit extension cannula 70 to be advanced through a conventional ECMO reperfusion cannula so that distal region 71 of expandable conduit 72 may be disposed with its outlet extending beyond a patient’s renal arteries, and preferably extending in a patient’s ascending aorta or in the vicinity of the aortic arch.
• hypotube 77 may have a lumen sized and shaped to receive a guidewire therethrough, such that extension cannula 70 may be advanced through the conventional ECMO reperfusion cannula to the target location over a guidewire via the lumen of hypotube 77.
• hypotube 77 may include an anti-thrombolytic coating.
• Extension cannula 70 optionally may include handle 75 coupled to hypotube 77 at proximal region 73 of extension cannula 70 for maneuvering extension cannula 70.
• connection structure 79 may be self-expandable between a collapsed delivery state and an expanded deployed state, e.g., upon exposure from sheath 40. As shown in FIGS. 7A and 7B, connection structure 79 may have a curved shape in the expanded deployed state. Connection structure 79 may be embedded within the biocompatible material forming expanding conduit 72. Additionally or alternatively, connection structure 79 may be coupled to the inner surface of expandable conduit 72 or to the outer surface of expandable conduit 72, or both.
• connection structure 79 is not self-expandable, such that connection structure 79 transitions from the collapsed delivery state to the expanded deployed state when blood flows through the lumen of expandable conduit 72, thereby causing expandable conduit 72 to fill with blood.
• Expandable conduit 72 is made of a soft flexible material, such as polyethylene, polyurethane, or nylon, and may include pores 74 at its distal region that permit blood to perfuse through the material as the flow is directed through the lumen of expandable conduit 72.
• expandable conduit 72 has inlet 76 at its proximal end and an outlet, e.g., plurality of pores 74, at its distal region, and a lumen extending therethrough for permitting blood flow.
• Pores 74 may be sized and shaped such that, as blood flows from the ECMO machine and through the conventional ECMO reperfusion cannula and the lumen of expandable conduit 72, the blood flow exits expandable conduit 72 via pores 74, while causing expandable conduit 72 to fill with blood and transition from a collapsed delivery state, as shown in FIG. 7A, to the expanded deployed state, as shown in FIG. 7B.
• expandable conduit 72 has a length sufficient to extend from the outlet of the conventional ECMO reperfusion cannula to a position above the patient’s renal arteries, and more preferably, into the thoracic aorta, e.g., 15-120 cm, or preferably 20-80 cm or 30-50 cm.
• the lightweight sock-like structure provides advantages including, for example, ease of deployment through tortuous or diseased aortas, as well as no impingement on the spinal cord as most patients are lying flat such that use of a rigid cannula may impinge on the spinal cord.
• expandable conduit 72 may include a self-expanding support structure, e.g., anchoring stent 80, such as a mesh, weave or braid formed of a shape-memory metal or stainless steel, at its proximal end such that anchoring stent 80 may transition from a collapsed insertion state and an expanded deployed state within the lumen of the conventional ECMO reperfusion cannula to thereby anchor expandable conduit 72 within the conventional ECMO reperfusion cannula.
• anchoring stent 80 may be biased toward the expandable deployed state, such that anchoring stent 80 may self-expand upon exposure from sheath 40.
• Anchoring stent 80 may be covered by a flexible and biocompatible covering, or alternatively, anchoring stent 80 may be uncovered.
• Anchoring stent 80 may be formed of a stainless steel mesh, weave or braid having a preset expanded diameter that forms a central lumen, such that expandable conduit 72 may be contracted when pulled within smaller diameter delivery sheath 40.
• anchoring stent 80 may be a mesh, weave or braid formed of a shape-memory metal such as a nickel-titanium alloy (“Nitinol”), and having a predetermined expanded diameter that forms the internal lumen. In this way, expandable conduit 72 may be contracted to the collapsed insertion state when pulled within delivery sheath 40 as described in further detail below.
• anchoring stent 80 assumes a diameter substantially the same as, or even larger than, the internal lumen of a conventional VA-ECMO cannula.
• the lumen of anchoring stent 80 may be at least 15 Fr in the expanded state. Accordingly, when deployed within the lumen of the conventional ECMO cannula, anchoring stent 80 will expand to the diameter of the lumen of the conventional ECMO cannula, such that anchoring stent 80 will apply a radially outward force against the inner surface of the conventional ECMO cannula to thereby anchor anchoring stent 80 within the lumen of the conventional ECMO cannula.
• expandable conduit 72 When inserted through a conventional ECMO cannula and anchored to the conventional ECMO cannula via anchoring stent 80, expandable conduit 72 permits enhanced blood flow to the ascending aorta and aortic arch, while maintaining the diameter of the vascular opening in the femoral artery required to introduce the conventional VA-ECMO return cannula.
• the biocompatible polymer coating may include additional pores proximal to pores 74 that permit blood to perfuse laterally through the material, thereby reducing jetting from pores 74.
• expandable conduit 72 may include one or more radiopaque markers disposed along the distal end of expandable conduit 72 adjacent pores 74 to permit its location to be determined fluoroscopically.
• inlet 76 at the proximal end of expandable conduit 72 may have a feature for facilitating recapture of expandable conduit 72 within the delivery sheath.
• expandable conduit 72 may have a plurality of angled legs that couple anchoring stent 80 of expandable conduit 72 to shaft 77 to facilitate resheathing of expandable conduit 72 for removal.
• the angled legs are flexible and of uniform length, so that when the distal end of sheath 40 is advanced over the angled legs, the legs flex inward to cause anchoring stent 80 to collapse inward toward its collapsed delivery state.
• expandable conduit 72 when expandable conduit 72 does not have a feature for facilitating recapture of expandable conduit 72, expandable conduit 72 may be removed along with the conventional ECMO cannula by turning off the ECMO machine to stop blood flow into expandable conduit 72, thereby causing expandable conduit 72 to return to a semi-collapsed state. Accordingly, expandable conduit 72 and the conventional ECMO cannula may be removed together from the patient’ s vasculature.
• sheath 40 may have a rapid exchange configuration, with sheath 40 having a length suitable for covering the entire length of expandable conduit 72 but is joined to a support shaft and a handle coupled to the end of the support shaft. In this manner, sheath 40 may be back-loaded over the proximal end of shaft 77 of extension cannula 70 and manipulated using the support shaft via the handle, without interfering with the ability to manipulate the proximal end of shaft 77.
• FIGS. 8 A to 8C operation of the embodiment of the extension cannula of FIGS. 7 A and 7B is schematically depicted in conjunction with an optional in-line connector 20 of FIG. 3A.
• conventional ECMO cannula 60 may be coupled to outlet 24 of in-line connector 20 and inserted into a patient’s arterial vasculature, e.g., via a cut down to the femoral artery, as shown in FIG. 8A.
• the outlet line from an ECMO machine may be coupled to first branch inlet 22.
• extension cannula 70 disposed with expandable conduit 72 in its collapsed insertion state within delivery sheath 40, is advanced through the hemostatic valve of second branch inlet 26 of in-line connector 20.
• Extension cannula 70 is positioned so that the distal end of expandable conduit 72 is disposed in the desired location, c.g., within the thoracic aorta, and the proximal end of expandable conduit 72 lies near the distal outlet of the conventional ECMO reperfusion cannula, e.g., as may be determined under fluoroscopy using, e.g., radiopaque marker bands disposed on sheath 40.
• the lumen of sheath 40 preferably is dimensioned to accept and retain expandable conduit 72 in its collapsed insertion state.
• Sheath 40 is slidably disposed over expandable conduit 72, and accordingly anchoring stent 80 and connection structure 79, so that sheath 40 may be retracted relative to expandable conduit 72, thereby permitting connection structure 79 and/or anchoring stent 80 to transition from the collapsed delivery state to the expanded deployed state upon exposure from sheath 40.
• FIG. 8C when sheath 40 and expandable conduit 72 are positioned in the desired location as described above, sheath 40 is retracted while expandable conduit 72 is held in position by hypotube 77 and handle 75, thereby permitting connection structure 79 and/or anchoring stent 80 to transition to their expanded, deployed states. As shown in FIG. 8C, in its expanded deployed state, anchoring stent 80 abuts the inner surface of conventional ECMO reperfusion cannula 60 to thereby anchor expandable conduit 72 within conventional ECMO reperfusion cannula 60.
• expandable conduit 72 may fully transition to its expanded deployed state when in fluid communication with blood flow from the ECMO machine through conventional ECMO reperfusion cannula 60, as shown in FIG. 7B.
• expandable conduit 72 may have a diameter of 10-20 mm.
• expandable conduit 72 has a length between 15 to 120 cm or preferably, 20-80 cm or longer. In this manner, blood may be delivered in the vicinity of a patient’s thoracic aorta, above the patient’s renal artery ostia, to avoid high flow rates in the vicinity of the patient’s renal arteries and reduce the risk of perfusion injury.
• ECMO reperfusion cannula 60 may be shortened compared with conventional ECMO cannulas, e.g., 5- 15 cm, or preferably 8-10 cm.
• sheath 40 may be re-inserted over shaft 77 and advanced to collapse and retrieve expandable conduit 72.
• sheath 40 will first engage the plurality of angled legs that couple anchoring stent 80 of expandable conduit 72 to shaft 77, such that advancement of sheath 40 while retaining shaft 77 stationary will cause anchoring stent 80, and accordingly expandable conduit 72, to collapse inward and return to its reduced diameter, collapsed insertion state within sheath 40.
• FIG. 8D illustrates extension cannula 70 coupled to conventional ECMO reperfusion cannula 60 without in-line connector 20. As described above, in-line connector 20 is optional. Accordingly, the proximal end of conventional ECMO reperfusion cannula 60 may be coupled directly to the ECMO circuit.
• extension cannula 70 for improving perfusion during ECMO.
• method steps 51-56 of FIG. 5 described above may be used to deliver extension cannula 70 for improving perfusion during ECMO.
• the distal region of extension cannula 70 may be delivered to the target location within the thoracic aorta in a collapsed insertion state within sheath 40, as described above with regard to steps 51 and 52 of FIG. 5, and as illustrated by FIGS. 6A to 6C.
• conventional ECMO cannula 60 may be inserted through the patient’ s femoral artery FA coupled to ECMO machine 61 via outlet 24 and first inlet 22 of inline connector 20, and guidewire 62 may be inserted through second branch inlet 26 and outlet 24 of in-line connector 20, and through ECMO cannula 60 until the distal end of guidewire 62 is advanced to the desired location within the patient’s vasculature, e.g., within the thoracic aorta TA such as within the ascending aorta or in the vicinity of the aortic arch.
• the distal end of sheath 40 is advanced through ECMO cannula 60, e.g., over guidewire 62, via the lumen of hypotube 77 and in-line connector 20.
• the distal end of sheath 40 is advanced until it is positioned at the desired central location within the patient’s vasculature at step 52 as shown in FIG. 6C.
• FIG. 9A illustrates expandable conduit 72 in a semi-expanded state within the patient’s vasculature.
• FIG. 9B illustrates expandable conduit 72 fully expanded within the patient’s vasculature, e.g., when expandable conduit 72 is fully exposed from sheath 40 and blood flows from the ECMO machine through ECMO cannula 60 and into the lumen of expandable conduit 72.
• oxygenated blood may be perfused from ECMO cannula 60 to the central location within the patient’s vasculature, e.g., within the ascending aorta or in the vicinity of the aortic arch, via pores 74 at the distal region of expandable conduit 72.
• pores 74 of expandable conduit 72 may be positioned within the descending aorta, e.g., the portion of the descending aorta approaching the level of the diaphragm from beneath the thoracic cavity or the portion of the descending aorta above the diaphragm.
• expandable conduit 72 may be returned to the collapsed insertion state within the lumen of sheath 40 as described above, and at step 56, sheath 40 and expandable conduit 72 disposed therein may be removed from the patient.
• extension cannula 70 for improving perfusion during ECMO.
• method steps 51-56 of FIG. 5 described above may be used to deliver extension cannula 70 for improving perfusion during ECMO.
• the distal region of extension cannula 70 may be delivered to the target location within the thoracic aorta in a collapsed insertion state within sheath 40, as described above with regard to steps 51 and 52 of FIG. 5.
• conventional ECMO cannula 60 may be inserted through the patient’ s femoral artery FA.
• conventional ECMO cannula 60 is not yet coupled to ECMO machine 61 at this stage.
• guidewire 62 may be inserted through ECMO cannula 60 until the distal end of guidewire 62 is advanced to the desired location within the patient’s vasculature, e.g., within the thoracic aorta TA such as within the ascending aorta or in the vicinity of the aortic arch.
• the distal end of sheath 40 having expandable conduit 72 disposed therein in a collapsed insertion state, is advanced through ECMO cannula 60, e.g., over guidewire 62, via the lumen of hypotube 77.
• sheath 40 is advanced until it is positioned at the desired central location within the patient’s vasculature at step 52 as shown in FIG. 6C.
• Guidewire 62 may then be removed through the proximal end of hypotube 77.
• sheath 40 is retracted relative to expandable conduit 72 slidably disposed within the lumen of sheath 40, while expandable conduit 72 remains stationary, causing connection structure 79, and accordingly at least a portion of expandable conduit 72, to transition from the collapsed insertion state to an expanded deployed state upon exposure from sheath 40, as shown in FIG. 10A.
• FIG. 10A illustrates expandable conduit 72 in a semi-expanded state within the patient’s vasculature.
• Sheath 40 is further retracted relative to expandable conduit 72, causing anchoring stent 80 to transition from the collapsed insertion state to an expanded deployed state upon exposure from sheath 40 within ECMO cannula 60, thereby anchoring expandable conduit 72 to ECMO cannula 60.
• the proximal end of ECMO cannula 60 may then be coupled to ECMO machine 61, e.g., via tubing.
• FIG. 10B illustrates expandable conduit 72 fully expanded within the patient’s vasculature, c.g., when expandable conduit 72 is fully exposed from sheath 40 and blood flows from ECMO machine 61 through ECMO cannula 60 and into the lumen of expandable conduit 72.
• oxygenated blood may be perfused from ECMO cannula 60 to the central location within the patient’s vasculature, e.g., within the ascending aorta or in the vicinity of the aortic arch, via pores 74 at the distal region of expandable conduit 72.
• expandable conduit 72 may be returned to the collapsed insertion state within the lumen of sheath 40 as described above, and at step 56, sheath 40 and expandable conduit 72 disposed therein may be removed from the patient.
• Extension cannula 70' may be constructed similar to the extension cannula 70, except that the proximal end of expandable conduit 72' may be fixed to conventional ECMO reperfusion cannula 60' prior to insertion of extension cannula 70' into the patient. As shown in FIG. 11 A, the proximal end of expandable conduit 72' may be coupled to the inner surface of conventional ECMO reperfusion cannula 60' via coupling mechanism 81, e.g., an adhesive.
• coupling mechanism 81 e.g., an adhesive.
• the proximal end of expandable conduit 72' may be coupled to the inner surface of conventional ECMO reperfusion cannula 60' via heat sealing, 2-part polyurethane adhesive, and/or segmented polyurethane bonding.
• extension cannula 70', conventional ECMO reperfusion cannula 60', and in-line connector 20 arc advanced together into the patient, c.g., by guiding tip 78' of extension cannula 70' via hypotube I , to position pores 74' of expandable conduit 72' in the vicinity of the aortic root, as described in further detail below.
• FIG. 1 IB illustrates extension cannula 70' coupled to conventional ECMO reperfusion cannula 60' without in-line connector 20.
• in-line connector 20 is optional.
• the proximal end of conventional ECMO reperfusion cannula 60' may be coupled directly to the ECMO circuit.
• hypotube 77' may be positioned on a single side within the lumens of expandable conduit 72' and ECMO cannula 60'.
• FIG. 1 ID illustrates a cross-sectional view of extension cannula 70' along line D — D of FIG. 11B, FIG.
• FIG. 1 HE illustrates a cross-sectional view of extension cannula 70' along line E — E of FIG. 1 IB
• FIG. 1 IF illustrates a cross-sectional view of extension cannula 70' along line F — F of FIG. 1 IB.
• hypotube 77' may be positioned against an inner wall of ECMO cannula 60' within the proximal region of ECMO cannula 60'.
• FIG. 1 ID hypotube 77' may be positioned against an inner wall of ECMO cannula 60' within the proximal region of ECMO cannula 60'.
• hypotube 77' may be positioned against an inner wall of expandable conduit 72' within the distal region of ECMO cannula 60', e.g., adjacent to where expandable conduit 72' is coupled to ECMO cannula 60' via coupling mechanism 81. As shown in FIG. 1 ID, hypotube 77' may be positioned against an inner wall of expandable conduit 72' throughout the length of expandable conduit 72'. Accordingly, hypotube 77' may extend from tip 78', and along an inner surface of hypotube 77' toward ECMO cannula 60'.
• Connector 90 may have inlet 92 configured to be coupled to an outlet of a conventional ECMO machine for receiving oxygenated blood from an ECMO circuit, sidearm 93 extending at an angle from a side of connector 90, and outlet 91 configured to be coupled to a conventional ECMO cannula.
• Inlet 92 is in fluid communication with outlet 91, and may include an optional hemostatic valve 25, as described above with respect to FIG. 3B.
• the fluid pathway extending between inlet 92 and outlet 91 thus permits oxygenated blood received from an ECMO circuit to flow to through the conventional ECMO cannula and expandable conduit 72". As shown in FIG.
• inlet 92 may be co-linear with outlet 91.
• sidearm 93 is in fluid communication with the lumen of hypotube 77", and also may have an optional hemostatic valve welded therein. Accordingly, sidearm 93 may have a lumen sized and shaped to receive a guidewire therethrough.
• sidearm 93 and hypotubc 77" may be sized and shaped to receive a stylet therein, the stylet configured to be inserted through sidearm 93 and hypotube 77" to preserve the lumen of sidearm 93 and hypotube 77" during operation and prevent clotting therein.
• the proximal end of the stylet may be configured to releasably engage with sidearm 93 when the stylet is disposed therethrough, to thereby secure the stylet within sidearm 93, e.g., via a threaded engagement. Additionally, upon removal of the stylet, the guidewire may be reinserted through sidearm 93 and hypotube 77" for removal of extension cannula 70".
• FIG. 12 a flow chart of exemplary steps for improving perfusion during ECMO using any one of the extension cannulas of FIGS. 11 A to 11C is provided. Some of the steps of method 100 may be further elaborated by referring to FIGS. 13A and 13B, as well as FIGS. 14A to 15B, as described in further detail below.
• expandable conduit 72' is coupled to ECMO cannula 60' prior to insertion of extension cannula 70' and ECMO cannula 60' into the patient. Accordingly, referring to the extension cannula of FIG.
• hypotube 77' may extend from tip 78' proximally through the lumen of expandable conduit 72', the lumen of ECMO cannula 60', outlet 24 of in-line connector 20, and second branch inlet 26 of in-line connector 20.
• ECMO cannula 60' is coupled to ECMO machine 61 via outlet 24 and first inlet 22 of in-line connector 20.
• guidewire 62 may be inserted through hypotube 77' such that guidewire 62 passes through second branch inlet 26 and outlet 24 of in-line connector 20, through ECMO cannula 60', and through the lumen and tip 78' of expandable conduit 72'.
• Guidewire 62 may be advanced through an incision in the patient’s femoral artery FA until the distal end of guidewire 62 is advanced to the desired location within the patient’s vasculature, e.g., within the thoracic aorta TA such as within the ascending aorta or in the vicinity of the aortic arch.
• extension cannula 70' e.g., tip 78' of expandable conduit 72'
• extension cannula 70' is advanced over guidewire 62 via the lumen of hypotube 77', together with ECMO cannula 60' and in-line connector 20, as shown in FIG. 13A.
• Extension cannula 70', ECMO cannula 60', and in-line connector 20 are advanced until expandable conduit 72' is positioned at the desired central location within the patient’s vasculature at step 102, and ECMO cannula 60' is positioned within the patient’s femoral artery FA, as shown in FIG. 13B.
• oxygenated blood may be perfused from ECMO machine 61 through the lumen of expandable conduit 72' via in- line connector 20 and ECMO cannula 60', thereby causing expandable conduit 72' to fully expanded within the patient’s vasculature as shown in FIG. 13B, to the central location within the patient’s vasculature, e.g., within the ascending aorta or in the vicinity of the aortic arch, via pores 74' at the distal region of expandable conduit 72'.
• pores 74' of expandable conduit 72' may be positioned within the descending aorta, e.g., the portion of the descending aorta approaching the level of the diaphragm from beneath the thoracic cavity or the portion of the descending aorta above the diaphragm.
• the ECMO machine may be turned off, such that blood no longer flows through expandable conduit 72', thereby causing expandable conduit 72' to return to a semi-collapsed state, and at step 105, extension cannula 70' and ECMO cannula 60' may be removed from the patient.
• extension cannula 70' for improving perfusion during ECMO, without use of an in-line connector.
• distal end of extension cannula 70' e.g., tip 78' of expandable conduit 72'
• guidewire 62 is advanced over guidewire 62 via the lumen of hypotube 77', together with ECMO cannula 60, as shown in FIG. 14A.
• Extension cannula 70' and ECMO cannula 60' are advanced until expandable conduit 72' is positioned at the desired central location within the patient’s vasculature at step 102, and ECMO cannula 60' is positioned within the patient’s femoral artery FA, as shown in FIG. 14B.
• Guidewire 62 may then be removed through the proximal end of ECMO cannula 60', and the proximal end of ECMO cannula 60' may then be coupled to ECMO machine 61.
• oxygenated blood may be perfused from ECMO machine 61 through the lumen of expandable conduit 72' via ECMO cannula 60', thereby causing expandable conduit 72' to fully expanded within the patient’s vasculature as shown in FIG. 14B, to the central location within the patient’s vasculature, e.g., within the ascending aorta or in the vicinity of the aortic arch, via pores 74' at the distal region of expandable conduit 72'.
• the ECMO machine may be turned off, such that blood no longer flows through expandable conduit 72', thereby causing expandable conduit 72' to return to a semi-collapsed state, and at step 105, extension cannula 70' and ECMO cannula 60' may be removed from the patient.
• extension cannula 70" having connector 90 coupled thereto for improving perfusion during ECMO.
• the distal end of extension cannula 70 e.g., tip 78" of expandable conduit 72
• ECMO cannula 60" and connector 90 as shown in FIG. 15 A.
• Extension cannula 70" and ECMO cannula 60" are advanced until expandable conduit 72" is positioned at the desired central location within the patient’s vasculature at step 102, and ECMO cannula 60" is positioned within the patient’s femoral artery FA, such that guidewire 62 extends out of sidearm 93.
• Guidewire 62 may then be removed through sidearm 93.
• a stylet may then be inserted through sidearm 93 and hypotube 77", e.g., until the end of the stylet is adjacent to tip 78" of extension cannula 70", to thereby prevent blood from entering hypotube 77" and clotting therein during operation.
• the proximal end of the stylet may be releasably secured to sidearm 93 while the stylet is disposed therein, e.g., via a threaded engagement.
• an end cap may be coupled to sidearm 93.
• Inlet 92 of connector 90 may then be coupled to ECMO machine 61, as shown in FIG. 15B.
• oxygenated blood may be perfused from ECMO machine 61 through the lumen of expandable conduit 72" via connector 90 and ECMO cannula 60", thereby causing expandable conduit 72" to fully expanded within the patient’s vasculature as shown in FIG. 15B, to the central location within the patient’s vasculature, e.g., within the ascending aorta or in the vicinity of the aortic arch, via pores 74" at the distal region of expandable conduit 72".
• the ECMO machine may be turned off, such that blood no longer flows through expandable conduit 72", thereby causing expandable conduit 72" to return to a semi-collapsed state.
• the stylet may then be removed from sidearm 93 and hypotube 77", guidewire 62 may be reinserted through sidearm 93 and hypotube 77".
• extension cannula 70" and ECMO cannula 60" may be removed from the patient, e.g., over guidewire 62.
• existing long venous cannulas do not have a proximal side-connecting Fabric lock, and thus, if such long venous cannulas were to be used in the arterial position, it would not provide antegrade perfusion of the leg.
• existing arterial cannulas may include a proximal side-connecting Luer lock; however, such arterial cannulas are shorter than the existing long venous cannulas. Accordingly, the custom built extension cannulas described herein provide a proximal side connecting Luer lock on a long arterial cannula.
• Extension cannula 70"' may be constructed similar to the extension cannula 70, 70', 70" except that extension cannula 70"' may include one or more sensors 62 disposed on the distal region of expandable conduit 72'" for measuring one or more physiological parameters within the patient’s vasculature.
• sensors 62 may be a pressure sensor, flow sensor, and/or an oxygen saturation sensor.
• hypotube 77' may have another separate lumen extending therethrough, sized and shaped to receive electrical wires for coupling sensors 62 to console 63, e.g., via sidearm 93, for providing pressure and/or oxygen saturation readouts.
• a delivery system for delivering extension cannula 70' is provided.
• at least a portion of expandable conduit 72' may be disposed within peel-away introducer 85.
• introducer 85 may extend from tip 78' of expandable conduit 72' proximally toward the proximal region of expandable conduit 72'.
• introducer 85 extends along only a portion of expandable conduit 72'.
• introducer 85 may extend along the entire length of expandable conduit 72'.
• Introducer 85 preferably has a diameter that is equal to or slightly less than the diameter of ECMO cannula 60', such that when introducer 85 is inserted through the patient’s skin and into the artery, the arterial puncture is not larger than EMCO cannula 60' and insertion of ECMO cannula 60' into the arteriotomy after the peel-away introducer has been removed will be hemostatic without bleeding. Introducer 85 may be retracted proximally relative to expandable conduit 72' and peeled away from its proximal end as shown in FIG. 17B, external to the patient.
• peel-away introducer 85 also may be used to facilitate delivery of extension cannula 70" through the patient’s skin and into the artery.
• introducer 85 may extend from tip 78" of expandable conduit 72" proximally toward the proximal region of expandable conduit 72".
• introducer 85 extends along only a portion of expandable conduit 72".
• introducer 85 may extend along the entire length of expandable conduit 72".
• peel-away introducer may be used to facilitate delivery of the other extension cannulas described herein where the expandable conduit is prefixed to the ECMO cannula.
• introducer 85 may be used to deliver the extension cannulas described herein that are coupled to in-line connector 20.
• FIG. 18 a flow chart of exemplary steps for improving perfusion during ECMO using the delivery system of any one of FIGS. 17A to 17C is provided. Some of the steps of method 110 may be further elaborated by referring to FIGS. 19A to 19D, as described in further detail below.
• at least a portion of expandable conduit 72' is disposed within peel-away introducer 85, such that introducer 85 extends from tip 78' proximally towards the proximal region of expandable conduit 72'.
• guidewire 62 may be advanced through an incision in the patient’ s femoral artery FA until the distal end of guidewire 62 is advanced to the desired location within the patient’s vasculature, e.g., within the thoracic aorta TA such as within the ascending aorta or in the vicinity of the aortic arch.
• extension cannula 70' e.g., tip 78' of expandable conduit 72', disposed within introducer 85
• extension cannula 70', introducer 85, and ECMO cannula 60' are advanced until introducer 85 is positioned through the patient’s skin S and through femoral artery FA, such that the distal end of expandable conduit 72' is disposed within the artery.
• the proximal end of introducer 85 will remain external to the patient.
• introducer 85 may be disposed over only a portion of expandable conduit 72', and thus, when introducer 85 is inserted through the patient’s vasculature as far as it can be while its proximal end remains external to the patient, the distal end of expandable conduit 72' may not yet be disposed within the desired location within the patient’s vasculature, e.g., within the vicinity of the aortic arch. [0151] At step 113, introducer 85 may be retracted proximally relative to expandable conduit 72', while expandable conduit 72' remains stationary within the patient’s vasculature.
• introducer 85 As introducer 85 is retracted, it may simultaneously be peeled away from expandable conduit 72' along its proximal end, as shown in FIG. 19B, until introducer 85 is completely removed from expandable conduit 72', as shown in FIG. 19C.
• the extension cannula Once introducer 85 is completely removed from expandable conduit 72', at step 114, the extension cannula may be further inserted into the patient until the distal end of expandable conduit 72' is positioned at the desired central location within the patient’s vasculature, and ECMO cannula 60' is positioned within the patient’s femoral artery FA, as shown in FIG. 19D.
• Guidewire 62 may then be removed through the proximal end of ECMO cannula 60', and the proximal end of ECMO cannula 60' may then be coupled to ECMO machine 61.
• oxygenated blood may be perfused from ECMO machine 61 through the lumen of expandable conduit 72' via ECMO cannula 60', thereby causing expandable conduit 72' to fully expanded within the patient’s vasculature as shown in FIG. 19D, to the central location within the patient’s vasculature, e.g., within the ascending aorta or in the vicinity of the aortic arch, via pores 74' at the distal region of expandable conduit 72'.
• pores 74' of expandable conduit 72' may be positioned within the descending aorta, e.g., the portion of the descending aorta approaching the level of the diaphragm from beneath the thoracic cavity or the portion of the descending aorta above the diaphragm.
• the ECMO machine may be turned off, such that blood no longer flows through expandable conduit 72', thereby causing expandable conduit 72' to return to a semi-collapsed state, and at step 117, extension cannula 70' and ECMO cannula 60' may be removed from the patient.
• introducer 85 may extend along the entire length of expandable conduit 72'. Accordingly, when introducer 85 is inserted through the patient’s vasculature as far as it can be while its proximal end remains external to the patient, the distal end of expandable conduit 72' may be disposed within the desired location within the patient’s vasculature, e.g., within the vicinity of the aortic arch, such that upon removal of introducer 85 from expandable conduit 72', the extension cannula only needs to be further inserted into the patient until ECMO cannula 50' is positioned within the patient’s femoral artery FA.
• extension cannula 120 may include expandable conduit 122 and elongated shaft 123, e.g., a hypotube, extending from tip 121 at the distal end of extension cannula 120 towards the proximal end of extension cannula 120.
• Hypotube 123 is formed of a material, e.g., stainless steel rod, having sufficient rigidity to permit extension cannula 120 to be advanced through a conventional ECMO reperfusion cannula so that the distal region of expandable conduit 122 may be disposed with its outlet extending beyond a patient’s renal arteries, and preferably extending in a patient’s ascending aorta or in the vicinity of the aortic arch.
• hypotube 123 may have a lumen sized and shaped to receive a guidewire therethrough, such that extension cannula 120 may be advanced through the conventional ECMO reperfusion cannula to the target location over a guidewire via the lumen of hypotube 123. As shown in FIG.
• hypotube 123 may be positioned on a single, lateral side of expandable conduit 122.
• hypotube 123 may be positioned along an inner wall of expandable conduit 122. Accordingly, hypotube 123 may extend from tip 121, and along an inner surface of expandable conduit 122 toward the ECMO cannula. Moreover, hypotube 123 further may extend along an inner surface of the ECMO cannula. Accordingly, hypotube 123 is not in the blood flow path through the lumen of expandable conduit 122.
• hypotube 123 may extend from tip 121 along an outer surface of expandable conduit 122, and accordingly, along an outer surface of the ECMO cannula, or alternatively, hypotube 123 may be embedded within the biocompatible material forming expandable conduit 122, e.g., the membrane of expandable conduit 122, such that hypotube 123 extends from tip 121 and through the membrane of expandable conduit 122 towards the ECMO cannula, e.g., along an entire length of expandable conduit 122.
• the distal end of hypotube 123 may include atraumatic tip 121, which may be coupled to the distal region of expandable conduit 122.
• extension cannula 120 further may include circumferential support 124 positioned at the distal region of expandable conduit 122 to facilitate expansion of expandable conduit 122 within the patient’s vasculature.
• Support 124 may be self-expandable between a collapsed delivery state and an expanded deployed state, e.g., upon exposure from the delivery sheath. As shown in FIG. 20A, support 124 may have a circumferential profile in the expanded deployed state. Support 124 may be embedded within the biocompatible material forming expanding conduit 122.
• support 124 may be coupled to the inner surface of expandable conduit 122 or to the outer surface of expandable conduit 122, or both. Moreover, in some embodiments, support 124 may also be coupled to hypotube 123. In one embodiment, support 124 is not self-expandable, such that support 124 transitions from the collapsed delivery state to the expanded deployed state when blood flows through the lumen of expandable conduit 124, thereby causing expandable conduit 122 to fill with blood. In some embodiments, extension cannula 120 may not include support 124.
• Expandable conduit 122 is made of a soft flexible material, such as polyethylene, polyurethane, or nylon, and may include a plurality of pores 125 at its distal region that permit blood to perfuse through the material as the flow is directed through the lumen of expandable conduit 122. Pores 125 may be sized and shaped such that, as blood flows from the ECMO machine and through the conventional ECMO reperfusion cannula and the lumen of expandable conduit 122, the blood flow exits expandable conduit 122 via pores 125, while causing expandable conduit 122 to fill with blood and transition from a collapsed delivery state to the expanded deployed state.
• a soft flexible material such as polyethylene, polyurethane, or nylon
• the biocompatible polymer coating may include additional pores proximal to pores 125 that permit blood to perfuse laterally through the material, thereby reducing jetting from pores 125.
• expandable conduit 122 has a length sufficient to extend from the outlet of the conventional ECMO reperfusion cannula to a position above the patient’s renal arteries, and more preferably, into the thoracic aorta, e.g., 15- 120 cm, or preferably 20-80 cm or 30-50 cm.
• the lightweight sock-like structure provides advantages including, for example, ease of deployment through tortuous or diseased aortas, as well as no impingement on the spinal cord as most patients are lying flat such that use of a rigid cannula may impinge on the spinal cord.
• the expandable conduit may include one or more longitudinally extending vents disposed along the tapered portion of the expandable conduit extending proximally from the tip and/or one or more vents disposed on the tip.
• Extension cannula 120' may be constructed similar to extension cannula 120, except that extension cannula 120' further may include connection structure 126, e.g., one or more umbrellalike struts, extending between tip 121' and support 124' to thereby provide reinforcement support at the distal region of extension cannula 120'.
• Connection structure 126 may be self-expandable between a collapsed delivery state and an expanded deployed state, e.g., upon exposure from the delivery sheath. As shown in FIG. 20B, connection structure 126 may have a linear shape in the expanded deployed state. Connection structure 126 may be embedded within the biocompatible material forming expanding conduit 122'.
• connection structure 126 may be coupled to the inner surface of expandable conduit 122' or to the outer surface of expandable conduit 122', or both.
• connection structure 126 is not selfexpandable, such that connection structure 126 transitions from the collapsed delivery state to the expanded deployed state when blood flows through the lumen of expandable conduit 122', thereby causing expandable conduit 122' to fill with blood.
• extension cannula 130 may include expandable conduit 132 and elongated shaft 133, e.g., a hypotube, extending from atraumatic tip 131 at the distal end of extension cannula 130 towards the proximal end of extension cannula 130.
• Hypotube 133 is formed of a material, e.g., stainless steel rod, having sufficient rigidity to permit extension cannula 130 to be advanced through a conventional ECMO reperfusion cannula so that the distal region of expandable conduit 132 may be disposed with its outlet extending beyond a patient’s renal arteries, and preferably extending in a patient’s ascending aorta or in the vicinity of the aortic arch.
• hypotube 133 may have a lumen sized and shaped to receive a guidewire therethrough, such that extension cannula 130 may be advanced through the conventional ECMO reperfusion cannula to the target location over a guidewire via the lumen of hypotube 133. As shown in FIG.
• hypotube 133 may be positioned at a central position within the lumen of expandable conduit 132. Specifically, as shown in FIG. 21A, hypotube 133 may extend along the longitudinal axis of extension cannula 130, while centered within the lumen of expandable conduit 132 to provide more stability in terms of cannula movement in the aorta. Accordingly, hypotubc 133 may extend from tip 131, and through the lumen of expandable conduit 133 toward the ECMO cannula. Moreover, hypotube 133 further may extend through the lumen of the ECMO cannula. Hypotube 133 does not form part of the blood flow path through the lumen of expandable conduit 132.
• Expandable conduit 132 is made of a soft flexible material, such as polyethylene, polyurethane, or nylon, and may include a plurality of pores 135 at its distal region that permit blood to perfuse through the material as the flow is directed through the lumen of expandable conduit 132. Pores 135 may be sized and shaped such that, as blood flows from the ECMO machine and through the conventional ECMO reperfusion cannula and the lumen of expandable conduit 132, the blood flow exits expandable conduit 132 via pores 135, while causing expandable conduit 132 to fill with blood and transition from a collapsed delivery state to the expanded deployed state.
• a soft flexible material such as polyethylene, polyurethane, or nylon
• the biocompatible polymer coating may include additional pores proximal to pores 135 that permit blood to perfuse laterally through the material, thereby reducing jetting from pores 135.
• expandable conduit 132 has a length sufficient to extend from the outlet of the conventional ECMO reperfusion cannula to a position above the patient’s renal arteries, and more preferably, into the thoracic aorta, e.g., 15- 120 cm, or preferably 20-80 cm or 30-50 cm.
• the lightweight sock-like structure provides advantages including, for example, ease of deployment through tortuous or diseased aortas, as well as no impingement on the spinal cord as most patients are lying flat such that use of a rigid cannula may impinge on the spinal cord.
• the expandable conduit may include one or more longitudinally extending vents disposed along the tapered portion of the expandable conduit extending proximally from the tip and/or one or more vents disposed on the tip.
• Extension cannula 130' may be constructed similar to extension cannula 130, except that extension cannula 130' further may include circumferential support 134 and connection structure 136, e.g., one or more umbrella-like struts, extending between tip 131' and support 134 to thereby provide reinforcement support at the distal region of extension cannula 130'.
• connection structure 136 e.g., one or more umbrella-like struts
• support 134 may be positioned at the distal region of expandable conduit 132' to facilitate expansion of expandable conduit 132' within the patient’s vasculature.
• Support 134 may be self-expandable between a collapsed delivery state and an expanded deployed state, e.g., upon exposure from the delivery sheath. As shown in FIG. 2 IB, support 134 may have a circumferential profile in the expanded deployed state. Support 134 may be embedded within the biocompatible material forming expanding conduit 132'. Additionally or alternatively, support 134 may be coupled to the inner surface of expandable conduit 132' or to the outer surface of expandable conduit 132', or both. In one embodiment, support 134 is not selfexpandable, such that support 134 transitions from the collapsed delivery state to the expanded deployed state when blood flows through the lumen of expandable conduit 134, thereby causing expandable conduit 132' to fill with blood. In some embodiments, extension cannula 130 of FIG. 21A also may include a circumferential support.
• Connection structure 136 may be self-expandable between a collapsed delivery state and an expanded deployed state, e.g., upon exposure from the delivery sheath. As shown in FIG. 21B, connection structure 136 may have a linear shape in the expanded deployed state, alternatively, connection structure 136 may have a curved shape in the expanded deployed state. Connection structure 136 may be embedded within the biocompatible material forming expanding conduit 132'. Additionally or alternatively, connection structure 136 may be coupled to the inner surface of expandable conduit 132' or to the outer surface of expandable conduit 132', or both.
• connection structure 136 is not self-expandable, such that connection structure 136 transitions from the collapsed delivery state to the expanded deployed state when blood flows through the lumen of expandable conduit 132', thereby causing expandable conduit 132' to fill with blood.
• the extension cannulas described herein may include various arrangements and configurations of pores disposed on at least the distal region of the expandable conduit, the pores sized and shaped to permit blood flow therethrough to thereby avoid blood stasis or clotting along the length of the cannula and to more evenly distribute flow in the aorta, thereby also avoiding loading of the left ventricle.
• the plurality of pores may include first plurality of pores 74a and second plurality of pores 74b, which may have a longitudinally extending shape, e.g., oval shape.
• pores 74a and pores 74b may be arranged laterally along the length of at least the distal region of the expandable conduit, e.g., expandable conduit 72, such that pores 74b are proximal to pores 74a.
• pores 74a may be disposed spatially apart from each other along the expandable conduit by a distance that is less than the distance pores 74b are spatially disposed apart by along the expandable conduit.
• the plurality of pores may include pores 74c, which may have a longitudinally extending shape, e.g., oval shape, and may be equally spatially disposed from each other along the length of at least the distal region of the expandable conduit, e.g., expandable conduit 72.
• the plurality of pores may include first plurality of pores 74d and second plurality of pores 74e.
• Pores 74d may have a circular shape, and may be disposed circumferentially about at least the distal region of the expandable conduit, e.g., expandable conduit 72.
• plurality of pores 74d may include multiple rows of circumferentially disposed pores.
• FIG. 22C illustrates four rows of circumferentially disposed pores 74d, as will be understood by a person having ordinary skill in the art, pores 74d may include less or more than four rows of circumferentially disposed pores.
• pores 74e may include multiple pores arranged laterally along the length of at least the distal region of the expandable conduit. As shown in FIG. 22C, pores 74e may be proximal to pores 74d. As will be understood by a person having ordinary skill in the art, the plurality of pores described herein may have any combination of the arrangements and configurations described above. For example, the laterally disposed pores may have a circular shape, and the circumferentially disposed pores may have a longitudinally extending shape, or any combination thereof.
• Extension cannula 120" may be constructed similar to extension cannula 120, 120'.
• extension cannula 120" may include expandable conduit 122" coupled to and extending proximally from tip 121", and hypotube 123" coupling to and extending proximally from tip 121" along a lateral side of expandable conduit 122".
• hypotube 123" may extend along an inner surface of expandable conduit 122", along an outer surface of expandable conduit 122", or may embedded within the membrane of expandable conduit 122" such that hypotube 123" extends within expandable conduit 122", e.g., along an entire length of expandable conduit 122".
• expandable conduit 122" may include a plurality of pores (not shown) disposed on at least the distal region of expandable conduit 122", the pores sized and shaped to permit blood flow therethrough to thereby avoid blood stasis or clotting along the length of the cannula and to more evenly distribute flow in the aorta, thereby also avoiding loading of the left ventricle.
• the pores may be disposed on the distal region of expandable conduit 122" proximal to support 124", if any, and/or on the tapered portion distal to support 124", e.g., between adjacent outflow vents 127.
• Extension cannula 120" differs from extension cannula 120, 120' in that extension cannula 120" further may include one or more outflow vents 127 disposed on at least the tapered portion of expandable conduit 122", e.g., the portion of expandable conduit 122" where its cross- sectional area decreases in the distal direction towards tip 121", and sized and shaped to permit blood flow therethrough, e.g., from within the lumen of expandable conduit 122" and into the patient’s vasculature. As shown in FIG. 23 A, outflow vents 127 may be arranged circumferentially around the tapered portion of expandable conduit 122", and extend longitudinally along the tapered portion having a slit-like geometry.
• outflow vents 127 may have other longitudinally extending shapes, e.g., ovals, rectangles, trapezoidal, etc.
• the width of outflow vents 127 increases in the proximal direction from tip 121" to improve flow therethrough.
• extension cannula 120" may include one or more holes 128 extending through tip 121", and sized and shaped to permit blood flow therethrough, e.g., from within the lumen of expandable conduit 122" and into the patient’s vasculature.
• holes 128 may be formed by drilling through tip 121". By permitting blood flow through holes 128, flow may be maintained and stasis removed from that region, thereby preventing and/or reducing clot formation within the distal end of expandable conduit 122", e.g., between the distal end of outflow vents 127 and the interior surface of tip 111".
• extension cannulas 70, 70', 70", 70"' may be incorporated into other extension cannulas described herein, e.g., extension cannulas 70, 70', 70", 70"'.
• Extension cannula 130" may be constructed similar to extension cannula 130, 130'.
• extension cannula 130" may include expandable conduit 132" coupled to and extending proximally from tip 131", and hypotube 133" coupling to and extending proximally from tip 131" along a central longitudinal axis of expandable conduit 122".
• expandable conduit 132" may include a plurality of pores (not shown) disposed on at least the distal region of expandable conduit 132", the pores sized and shaped to permit blood flow therethrough to thereby avoid blood stasis or clotting along the length of the cannula and to more evenly distribute flow in the aorta, thereby also avoiding loading of the left ventricle.
• the pores may be disposed on the distal region of expandable conduit 132" proximal to outflow vents 137 and/or on the tapered portion, e.g., between adjacent outflow vents 137.
• Extension cannula 130" differs from extension cannula 130, 130' in that extension cannula 130" further may include one or more outflow vents 137 disposed on at least the tapered portion of expandable conduit 132", c.g., the portion of expandable conduit 132" where its cross- sectional area decreases in the distal direction towards tip 131", and sized and shaped to permit blood flow therethrough, e.g., from within the lumen of expandable conduit 132" and into the patient’s vasculature. As shown in FIG. 23B, outflow vents 137 may be arranged circumferentially around the tapered portion of expandable conduit 132", and extend longitudinally along the tapered portion having a slit-like geometry.
• outflow vents 137 may have other longitudinally extending shapes, e.g., ovals, rectangles, triangles, etc.
• the width of outflow vents 137 increases in the proximal direction from tip 131" to improve flow therethrough.
• extension cannula 130" may include one or more holes 138 extending through tip 131", and sized and shaped to permit blood flow therethrough, e.g., from within the lumen of expandable conduit 132" and into the patient’s vasculature.
• holes 138 may be formed by drilling through tip 131".
• FIG. 24 is a graph illustrating stroke risk for patient’s undergoing various therapies include VA-ECMO.
• a patient undergoing VA-ECMO generally has the highest risk of total stroke, e.g., acute ischemic stroke and hemorrhagic stroke.
• the systems and methods described herein are expected to provide oxygenated blood to the cerebral vasculature and provide antegrade flow from the outlet of the self-expanding conduit. This in turn is expected to reduce the risk of ischemic stroke and reduce blood flow rates and pressures that could induce kidney injury.
• FIG. 25 illustrates a situation referred to as “north-south syndrome” that may arise in a patient on ECMO, particularly patients having compromised lung function.
• the blood returned to circulation by the left ventricle may be poorly oxygenated.
• oxygenated blood reperfused into the patient mixes with the antegrade flow of deoxygenated blood from the lungs, resulting in differential hypoxia.
• the extension cannula of the present invention is designed to deliver blood into the ascending aorta, the system and methods of the present invention are expected to significantly ameliorate the effect of compromised lung function and reduce the occurrence and severity of north-south syndrome.
• FIG. 26 is a series of graphs comparing various parameters measured during standard VA-ECMO cannulation and with use of the extension cannula of the present invention (defined as “Alternate Cannulation” in FIG. 26).
• the alternate cannulation of the present invention results in reduced pulmonary artery mean arterial pressure (MAP), reduced right arterial pressure, reduced pulmonary capillary wedge pressure, reduced renal arterial flow velocity, and reduced renal interstitial pressure (organ pressure), compared to standard VA-ECMO cannulation.
• MAP mean arterial pressure
• organ pressure reduced renal interstitial pressure
• an extension cannula may reduce cardiac, lung, and kidney injury when compared to standard VA-ECMO alone.
• this data shows reduced heart pressures (right atrial pressure and pulmonary capillary wedge pressure), normal renal artery velocity, and normal renal interstitial (organ) pressures with alternate cannulation as opposed to standard cannulation (delivery of blood to the femoral artery).
• the alternate cannulation of the present invention provides increased pulsatile arterial flow in the renal artery and the femoral artery compared to standard VA-ECMO cannulation.
• standard femoral cannulation ECMO reduces renal and femoral artery pulse pressure, e.g., pulsatility.
• alternative cannulation delivery of blood to the thoracic aorta
• renal and femoral artery pulse pressure e.g., pulsatility.
• Improved physiologic pulsatility is further associated with less injury.
• FIGS. 28 and 29 provide further comparisons of use of the alternate cannulation of the present invention compared to standard ECMO cannulation, demonstrating improved renal arty pulsatility and reduced microvascular resistance in the kidney.
• alternate (irrigation) cannulation preserves pulsatility in the renal artery after three hours of pumping.
• FIG. 29 compared to standard cannulation, alternate (irrigation) cannulation preserves pulsatility (renal resistance index) and reduces renal arterial microvascular resistance in the renal artery after two and six hours of pumping.
• FIG. 28 and 29 provide further comparisons of use of the alternate cannulation of the present invention compared to standard ECMO cannulation, demonstrating improved renal arty pulsatility and reduced microvascular resistance in the kidney.
• ALT ECMO alternate cannulation of the present invention
• KIM-1 kidney injury molecule 1
• ALT ECMO is associated with lower (normal) levels of kidney injury marker in the urine.
• FIGS. 31A and 3 IB provide a further comparison of use of the alternate cannulation of the present invention compared to standard ECMO cannulation, demonstrating significant and unexpected reduction in both left and right ventricular workload.
• FIG. 31 A is a graph of measured Pressure versus Volume that includes traces for the left and right ventricles at 60- minutes post-infarct, immediately after commencement of arterial ECMO cannulation within the femoral artery at a standard sub-renal outlet location, and after ten minutes of standard arterial ECMO cannulation.
• the area within the respective Pressure versus Volume loops, referred to as “PVA”, is a measure of the work performed by the heart during the cardiac cycle.
• FIG. 31 A show that the pressure/volume loops for the left ventricle (LV) are substantially unchanged by ECMO reperfusion.
• the right ventricle (RV) also does not experience a significant reduction in workload after standard arterial ECMO cannulation.
• the left and right ventricular workload is substantially unchanged because introduction of continuous high flow below the renal arteries causes the blood column in the descending aorta to stagnate, which in turn causes the LV pressures to remain high.
• the heart must continue working to overcome the resistance to antegrade flow created by the ECMO-infused blood. Accordingly, during standard ECMO cannulation, femoral delivery of arterial blood pressurizes the entire aorta, thereby increasing the load against which the native heart must pump.
• both the left ventricle (LV) and the right ventricle (RV) experience a significant reduction in workload after commencement of ECMO activation, and thereafter, compared to standard arterial ECMO cannulation in FIG. 31A.
• the pressure/volume loops for the left ventricle (LV) significantly decrease, and the pressure/volume loops for the right ventricle (RV) decreases even more, thus illustrating the effectiveness of the extension cannula of the present invention in reducing cardiac workload during ECMO reperfusion.
• the significant decrease in left and right ventricular workload is due to the delivery of blood into the aortic arch, which enhances antegrade blood flow to the descending aorta as well as the arteries adjoining the aortic arch.
• the resulting forward flow which fully develops during the 10 minutes after commencement of ECMO reperfusion, unloads the LV, thereby causing lesser cardiac output, but at much lower pressure.
• the reduced load in the LV may assist blood transiting the lungs, further reducing RV workload.
• the arterial tree is not pressurized, thereby avoiding increased pressure load that the heart might otherwise have to work against, which allows for more effective venous drainage of the heart, and thus reduced RV and LV volumes, without the cost of increasing ventricular pressure.
• FIG. 32 are graphs illustrating pressure volume area (PVA), stroke work (SW), and end-diastolic pressure (EDP) associated with use of standard conventional VA-ECMO cannulation and the alternate extension cannulation of the present invention.
• PVA pressure volume area
• SW stroke work
• EDP end-diastolic pressure
• FIG. 32 illustrates infarct size associated with use of standard conventional ECMO cannulation and the alternate cannulation of the present invention.
• infarct size associated with use of the alternate extension cannulation of the present invention is much lower than the infarct sizes associated with standard ischemia and reperfusion injury (IRI) and with use of standard conventional ECMO cannulation.
• IRI infarct sizes associated with standard ischemia and reperfusion injury
• FIG. 34 are graphs illustrating oxygen consumption rate (OCR) associated with standard ischemia and reperfusion injury (IRI) and use of standard conventional ECMO cannulation, with and without an Impella device, and the alternate extension cannulation of the present invention, which is indicative of the function of the mitochondria.
• OCR oxygen consumption rate
• IRI standard ischemia and reperfusion injury
• Impella device the alternate extension cannulation of the present invention, which is indicative of the function of the mitochondria.
• Mitochondria are known as the “powerhouse” of the cell, generating ATP via oxidative phosphorylation (OXPHOS) complexes, which are present in the inner membrane of mitochondria.
• NADH ubiquinone oxidorcductasc
• complex I succinate dehydrogenase
• complex II succinate dehydrogenase
• complex III ubiquinol-cytochrome c oxidoreductase
• complex IV cytochrome c oxidase
• complex V ATP synthase
• VA-ECMO used during a heart attack fails to reduce left heart workload and increases myocardial damage, and significantly reduces mitochondrial CI function. This effect of VA- ECMO cannot be rescued by placing an unloading pump after VA-ECMO has been initiated.
• use of the alternate extension cannulation of the present invention with VA-ECMO preserves function of mitochondrial CI, as measured by oxygen consumption rate (OCR), which when impaired, contributes to myocardial damage and infarct size.
• OCR oxygen consumption rate
• mitochondrial CI function is significantly reduced in the infarct zone after IRI alone, standard conventional VA-ECMO alone, and standard conventional VA-ECMO with an Impella device.
• mitochondrial CI function is significantly higher in the infarct zone after treatment using the alternate extension cannulation of the present invention with VA- ECMO.
• VV-ECMO venous-venous ECMO
• extension cannulas and in-line connectors described herein may be used in conjunction with a conventional ECMO drainage catheter such that the extension cannula extends from the drainage catheter at the femoral vein to within the pulmonary artery or right ventricle of the patient, thereby permitting blood to be pumped directly out of the heart, effectively functioning as a ventricular assist device.
• a conventional ECMO drainage catheter such that the extension cannula extends from the drainage catheter at the femoral vein to within the pulmonary artery or right ventricle of the patient, thereby permitting blood to be pumped directly out of the heart, effectively functioning as a ventricular assist device.
• any of the extension cannulas described herein e.g., extension cannula 10, 10', 10", 10", 70, 70', 70", 110, 100', 120, 120', may be used in conjunction with conventional ECMO drainage catheter 200 in fluid communication with ECMO drainage machine 201, such that the pores of the expandable conduit, e.g., pores 74 of expandable conduit 72, arc disposed within the pulmonary artery PA.
• the pores of the expandable conduit e.g., pores 74 of expandable conduit 72, arc disposed within the pulmonary artery PA.
• the extension cannula may be inserted via a femoral vein approach and have a length such that expandable conduit 72 extends through the femoral vein, inferior vena cava IVC, right atrium RA, and right ventricle RV, and pores 74 are disposed within pulmonary artery PA. Accordingly, the extension cannula may provide right heart support by draining blood from or delivering blood to the pulmonary artery PA via pores 74 through expandable conduit 72. In some embodiments, the extension cannula may have a length such that pores 74 are disposed within right ventricle RV, to thereby drain blood from or deliver blood to the right ventricle RV.
• the extension cannula may have a length such that the distal end of the extension cannula is disposed within pulmonary artery PA, and pores 74 are arranged at the distal region of the extension cannula such that pores 74 are disposed within both pulmonary artery PA and right ventricle RV, to thereby drain blood from or deliver blood to both pulmonary artery PA and right ventricle RV.
• the extension cannula may be inserted via an internal jugular vein approach and have a length such that expandable conduit 72 extends through the internal jugular vein, superior vena cava SVC, right atrium RA, and right ventricle RV, and pores 74 are disposed within pulmonary artery PA. Accordingly, the extension cannula may provide right heart support by draining blood from or delivering blood to the pulmonary artery PA via pores 74 through expandable conduit 72. In some embodiments, the extension cannula may have a length such that pores 74 are disposed within right ventricle RV, to thereby drain blood from or deliver blood to the right ventricle RV.
• the extension cannula may have a length such that the distal end of the extension cannula is disposed within pulmonary artery PA, and pores 74 are arranged at the distal region of the extension cannula such that pores 74 are disposed within both pulmonary artery PA and right ventricle RV, to thereby drain blood from or deliver blood to both pulmonary artery PA and right ventricle RV.
• the extension cannulas described above for use with a conventional ECMO cannula for delivering oxygenated blood directly to a location above the patient’s renal veins also may have a length such that the distal end region of the extension cannula, and accordingly the pores of the expandable conduit, are disposed within the pulmonary artery and/or the right ventricle, such that oxygenated blood may be delivered directly to the pulmonary artery and/or the right ventricle, respectively.

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• 2023
  • 2023-05-12 EP EP23732312.6A patent/EP4522242A1/de active Pending
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