Expandable Cannula System for ECMO

Abstract

An extension cannula and in-line connector for use with a conventional ECMO return cannula is provided. The extension cannula includes a flexible conduit that is transitionable between a collapsed, inserted state and an expanded, deployed state when in communication with blood flow from the ECMO machine via the ECMO return cannula. The extension cannula may be positioned through the conventional ECMO return cannula such that a proximal end of the flexible conduit is positioned within and proximal to the end of the ECMO return cannula while a distal end of the flexible conduit is positioned within the patient's thoracic aorta and delivers oxygenated blood directly to the patient's thoracic aorta via one or more pores in a distal region of the flexible conduit to improve cerebral oxygenation, maintain systemic arterial pulsatility, and reduce the potential for end-organ damage.

Description

[Technical field]

[0001] (CROSS REFERENCE TO RELATED APPLICATIONS) This application claims the benefit of priority to U.S. Patent Application No. 18 / 151,982, filed January 9, 2023, which claims the benefit of priority to U.S. Patent Application No. 17 / 663,205, filed May 12, 2022, now U.S. Patent No. 11,547,786, the entire contents of each of which are incorporated herein by reference. This application also claims the benefit of priority to U.S. Patent Application No. PCT / US2021 / 025461, filed April 1, 2021, which claims the benefit of priority to U.S. Patent Application No. 16 / 840,284, filed April 3, 2020, now U.S. Patent No. 11,331,421, the entire contents of each of which are incorporated herein by reference.

[0002] (Technical field) The present application relates generally to systems and methods for improving systemic perfusion and reducing complications during veno-arterial extracorporeal membrane oxygenation (VA-ECMO), and more specifically to systems and methods for improving perfusion that deliver oxygenated blood directly to the thoracic aorta using an in-line connector and extension cannula. [Background technology]

[0003] Approximately 23 million people worldwide suffer from heart failure (HF), which affects approximately 7 million individuals in the United States, with health care expenditures reaching approximately $40 billion per year. Acute myocardial infarction (AMI) is the leading cause of HF, occurring in more than 650,000 individuals per year in the United States. Despite early revascularization of AMI, there is a 20% increase in 1-year mortality and hospitalization for HF for every 5% increase in infarct size. Paradoxically, coronary reperfusion may hasten myocardial injury and myocardial cell death in AMI. Despite improvements in reperfusion times, subsequent HF remains a significant problem, and new approaches are needed to reduce myocardial damage in AMI.

[0004] Arterial perfusion to all major organ systems, including the heart, kidneys, and brain, is determined by arterial pressure, blood flow, vascular tone, and intraorgan vascular resistance. When patients suffer from low arterial perfusion due to heart failure, cardiopulmonary failure, and cardiogenic or septic shock, venoarterial extracorporeal membrane oxygenation (VA-ECMO) systems can be used to provide both circulatory and gas exchange support by enhancing the flow of oxygenated blood. See, for example, Pavlushkov E, Berman M, Valchanov K. Cannulation techniques for extracorporeal life support. Ann Transl Med 2017;5(4):70. doi: 10.21037 / atm.2016.11.47. Specifically, VA-ECMO drains blood from the venous system, oxygenates the blood outside the patient, and then returns the oxygenated blood to the arterial system, for example, 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. Large bore ECMO cannulas for use in adult humans generally range in diameter from 15 French (5.0 mm) to 25 French (8.3 mm) and are used to deliver life-sustaining blood flows of 3 to 8 liters per minute.

[0005] Despite the increased utilization of VA-ECMO (approximately 5,000 extracorporeal membrane oxygenation devices are used annually in the United States alone), in-hospital mortality remains at approximately 60%. One explanation for these poor outcomes is that peripherally cannulated VA-ECMO can cause kidney failure, increase the risk of stroke, and promote cerebral ischemia, hemorrhage, and vascular injury. In addition, two or more large-bore cannulas may be required to achieve the high flow rates required for systemic perfusion with VA-ECMO. Cannula number and size are directly associated with increased risk of hemorrhage, vascular trauma, and acute limb ischemia. Finally, peripherally cannulated VA-ECMO can pressurize the entire aorta and increase pressure inside the heart, which increases ventricular wall stress and myocardial oxygen consumption, thereby expanding infarct size in the setting of myocardial injury or heart attack, and increasing fluid in the lungs, thereby causing acute lung injury. Recent data also indicate that VA-ECMO may cause damage to mitochondria located in the heart, which may limit myocardial recovery. To mitigate cardiac or pulmonary injury, concomitant devices such as intra-aortic balloon pumps and Impella® pumps (marketed by Abiomed, Danvers, Massachusetts) may be used concomitantly with VA-ECMO and require additional vascular puncture. All of these complications are associated with increased mortality, long-term morbidity, length of stay in hospital, and health care costs. New approaches to limit the complications associated with VA-ECMO are required.

[0006] Studies have shown that VA-ECMO support can decrease renal function and even cause acute kidney injury due to increased arterial pressure and loss of pulsatile flow to the kidney resulting from high blood flow limited to the exit area of ​​the arterial outlet return cannula with conventional VA-ECMO. Such injury can then activate the kidney's autoregulatory mechanisms. For example, it has been observed that the high non-pulsatile flow encountered with conventional VA-ECMO cannula increases vascular resistance, which in turn increases renal work and worsens oxygen consumption. Up to 70% of patients undergoing VA-ECMO develop acute kidney injury, which is directly associated with mortality. Studies have further shown that the use of VA-ECMO leads to a significant increase in arterial flow and can promote an increase in pressure within the organ itself, which in turn reduces flow in the renal vein. Thus, the net effect of using VA-ECMO with conventional return cannula is an increase in pressure inside the organ such that flow through the kidney is reduced. These physiological findings correlate with increases in biomarkers of kidney damage, suggesting that one mechanism involved in kidney damage may be related to increased pressure inside the kidney and a net decrease in blood flow through the kidney.

[0007] Previous efforts to reduce perfusion impairment are known in the art. For example, U.S. Patent No. 6,083,198 to Afzal describes a perfusion catheter with divided flow regions in which the arterial return catheter includes a series of openings along its length to distribute blood more evenly within the aorta, including the aortic arch. However, one disadvantage of the system described in that patent is that the inner catheter includes a reduced diameter than the outer catheter, thereby reducing flow rate to the most distal portion of the catheter.

[0008] Recent studies have also shown that VA-ECMO use results in an increased risk of stroke, e.g., acute ischemic stroke and hemorrhagic stroke. Because VA-ECMO induces retrograde blood flow in the femoral artery toward the aorta, the brain is the last vital organ to receive oxygenated blood delivered via a conventional femoral artery cannula. Furthermore, in patients exhibiting North-South syndrome, for example, when impaired pulmonary function results in ejection of deoxygenated blood from the left ventricle into the ascending aorta, differential hypoxia can result as a result of VA-ECMO patients' reliance on retrograde flow to deliver oxygenated blood to the upper body. To mitigate this effect, physicians currently perform additional vascular punctures in arteries or veins and place additional large-bore cannulas that increase the risk of complications.

[0009] Central VA-ECMO, in which oxygenated blood is delivered directly to a central location, for example, via a surgical incision to the aortic arch, has been hypothesized to provide more oxygenated blood flow to the brain and therefore reduce the risk of stroke. However, such cannulation requires invasive surgery and carries additional potential complications, as described, for example, in U.S. Patent No. 6,210,365 to Afzal. Another theorized solution would be to deliver oxygenated blood directly to the patient's venous side via an ECMO cannula. However, that would require an additional large-bore puncture to be created in the patient's vasculature, which may be further complicated by the already existing cannula in the venous circulation from the original VA-ECMO configuration. In addition, placement of a rigid cannula from a peripheral artery into a central location within the thoracic aorta may be limited by the inability to navigate a large bore cannula through the iliac-femoral bifurcation, a tortuous aorta, or across a calcified aorta with atheromatous material affixed to the aorta.

[0010] In light of the foregoing, it would be desirable to provide systems and methods for delivering oxygenated blood via VA-ECMO from an entry point in the femoral artery to a more central location in the patient, such as the thoracic aorta, to supply the oxygenated blood to the brain and induce antegrade flow to the lower portion of the descending aorta. Such systems and methods may therefore improve blood flow to the brain, preserve brain function, reduce the risk of ischemic stroke, and reduce blood flow and pressure that may induce kidney damage.

[0011] U.S. Patent No. 8,996,095 to Anderson describes a coronary guide extension catheter having a push member and a distal tubular member 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 the coronary guide catheter during an interventional procedure and prevent migration away from the patient's ostium due to the beating of the heart. Similarly, U.S. Patent No. 10,485,956 to O'Donovan describes a guide extension catheter having grooves in the push member and a distal shaft for guiding an interventional coronary device. Such coronary guide extension catheters are unsuitable for use as perfusion cannulas in VA-ECMO due to the small lumen diameter and the resulting low blood flow that can be achieved. Guide extension catheters typically have a fixed diameter of 6 French (2 mm) to 8 French (2.7 mm). These coronary guide extension catheters are not intended to redirect blood flow, but rather to facilitate the delivery of coronary devices into distal portions of the coronary vasculature.

[0012] US Patent No. 6,632,236 to Hogendijk describes a self-expanding catheter for use in stent delivery, in which the catheter is transluminally inserted in a collapsed delivery state and self-expands to an expanded deployed state upon removal of the delivery sheath. The patent describes a self-expanding anchor formed from a self-expanding wire fabric having an elastomeric polymer coating and configured to protect against embolism during vascular intervention. The concept described in Hogendijk is intended to filter elements in the bloodstream rather than redirecting the bloodstream. Similarly, US Patent No. 6,183,443 to Kratoska describes an expandable introducer sheath for percutaneously introducing an endovascular angioplasty catheter. Such self-expanding catheters have not been contemplated for use with VA-ECMO systems for perfusing oxygenated blood.

[0013] In light of the disadvantages of known ECMO perfusion catheters, it would be desirable to provide a device for use with ECMO systems that could increase blood flow to the thoracic aorta and aortic arch, improve cerebral oxygenation, maintain systemic arterial pulsatility, and reduce the potential for perfusion compromise to the kidneys, using a single access port, thereby avoiding the bleeding and vascular compromise associated with contemporary VA-ECMO.

[0014] Additionally, it would be desirable to provide a device for use with ECMO systems that avoids the small flow lumen size of previously known reperfusion catheters, thereby allowing increased blood flow to the ascending aorta and aortic arch, while maintaining or reducing the diameter of the vascular opening into the femoral artery required for introduction of a return cannula.

[0015] In modern practice, VA-ECMO is also used to support commonly performed life-saving procedures such as coronary angioplasty, aortic valvuloplasty, or aortic valve replacement. However, the main limitation of these approaches is the need for additional vascular access to place vascular sheaths and / or catheters for the required interventional devices in addition to the existing VA-ECMO circuit. This can be prohibitive for patients with peripheral vascular disease, concomitant vascular disorders, or vasculature occupied by other life-saving devices. Moreover, under emergency conditions, placing additional vascular access can be difficult and increase the risk of failure.

[0016] US Patent Nos. 5,125,903, 5,195,980, 5,269,764, and 7,938,809 describe percutaneous catheter introducers / connectors with hemostatic valves to allow passage of elongated interventional devices into the patient's vasculature and side ports for connection to external sources, e.g., irrigation, suction, contrast, drugs, etc. These systems are not designed for use with VA-ECMO. Furthermore, none of the existing approaches allow simple and effective access to the VA-ECMO circuit for delivery of additional interventional equipment. Current Y-connectors used to provide access to the ECMO circuit suffer from a number of disadvantages, including a reduction in the effective lumen of the ECMO return cannula creating undesirable pressure gradients, and difficult angulation requirements that prevent the introduction of additional catheters without risk of kinking or catheter blockage. Such known connectors require the introducer sheath to be inserted approximately 25-30 cm distally from normal due to the intervening connecting tubing, thereby limiting access to the thoracic aorta, aortic root, aortic valve, or coronary vasculature for therapeutic intervention. Such connectors also pose a risk of bleeding during ECMO disconnection and reconnection, and there is an increased risk of air embolism and contamination due to disconnection from the ECMO circuit. See, e.g., Dmitriy S. Sulimov, MD et al., “Rescue Peripheral Intervention Using a Peripheral ECMO-Cannula as Vascular Access,” J Am Coll Cardiol Intv. 2020 Jan 9. Epublished DOI:10.1016 / j.jcin.2019.11.038.

[0017] It would therefore be desirable to provide a connector to provide simple and effective access to the ECMO circuit for delivery of interventional devices. [Prior art documents] [Patent documents]

[0018] [Patent Document 1] U.S. Pat. No. 8,996,095 [Patent Document 2] U.S. Patent No. 6,632,236 [Patent Document 3] U.S. Patent No. 5,125,903 [Non-patent literature]

[0019] [Non-Patent Document 1] Pavlushkov E,Berman M,Valchanov K. Cannulation techniques for extracorporeal life support. Ann Transl Med 2017;5(4):70. doi: 10.21037 / atm.2016.11.47 Summary of the Invention [Means for solving the problem]

[0020] In accordance with the principles of the present invention, devices and methods are provided for use with ECMO systems that overcome the disadvantages of previously known ECMO reperfusion catheters. Specifically, devices constructed in accordance with the present invention use a single access port to increase blood flow to the thoracic aorta, improve cerebral oxygenation, maintain systemic arterial pulsatility, and reduce the potential for end-organ damage.

[0021] According to one aspect of the present invention, an extension cannula is provided for use with an ECMO return cannula that defines a blood flow pathway. The extension cannula may include an ECMO return cannula, an elongated shaft, e.g., a hypotube, and a flexible sock-like conduit coupled to a distal region of the elongated shaft. The flexible conduit may be formed from at least one of a biocompatible fabric, e.g., polyethylene, polyurethane, or nylon, and the distal region of the flexible conduit may include a plurality of pores to allow blood flow to exit. In addition, the distal portion of the flexible conduit may include a tapered portion having a cross-sectional area that decreases toward the distal end of the flexible conduit such that an outlet of the flexible conduit may include one or more outflow holes disposed on at least the tapered portion of the flexible conduit. The one or more outflow holes may be disposed circumferentially around the tapered portion of the flexible conduit and may extend longitudinally along the tapered portion. For example, the width of the one or more outflow holes may increase in a proximal direction.

[0022] The proximal end of the flexible conduit may engage with the outlet of the ECMO return cannula to transition between a collapsed insertion state and an expanded deployed state when the flexible conduit communicates with blood flow from the ECMO machine through the internal lumen of the flexible conduit, forming a continuation of the blood flow path through the lumen of the ECMO return cannula. Preferably, the proximal end of the flexible conduit may be incorporated into a conventional ECMO return cannula as a single construction unit, whereby 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 to be positioned within the patient. Alternatively, in some embodiments, the proximal end of the flexible conduit may be removably coupled to a conventional ECMO return cannula, for example, via an expandable anchor, as described in more detail below, whereby the flexible conduit may be advanced through an ECMO return cannula positioned within the patient and expanded within the patient in the collapsed delivery state.

[0023] The extension cannula may further include a connecting structure, e.g., one or more umbrella struts, coupling the flexible conduit to a distal region of the elongate shaft. The elongate shaft may be used to advance the flexible conduit to position a distal end beyond the patient's renal vasculature, and the flexible conduit may have a length selected such that when the extension cannula is in an expanded, deployed state, the proximal end is located within the outlet of the ECMO return cannula at a location proximal to the patient's renal vasculature and the distal end extends beyond the outlet of the ECMO return cannula and beyond the patient's renal vasculature.

[0024] The elongate shaft may have a length selected such that the elongate shaft extends proximally from the tip, through the interior lumen of the flexible conduit, and beyond the proximal end of the flexible conduit. For example, the elongate shaft may extend proximally from the distal end of the flexible conduit along the side of the flexible conduit, or the elongate shaft may extend proximally within the lumen along the longitudinal axis of the flexible conduit from the distal end of the flexible conduit. Alternatively, at least a portion of the elongate shaft may be embedded within the membrane of the flexible conduit such that at least a portion of the elongate shaft may extend proximally within the flexible conduit from the distal end of the flexible conduit. Additionally, the tip may have one or more holes extending therethrough, the one or more holes sized and shaped to allow blood flow therethrough to mitigate formation of blood clots adjacent the tip within the flexible conduit.

[0025] In addition, the lumen of the elongated shaft may be sized and shaped to receive a guidewire therethrough. The elongated shaft may be configured such that the blood flow path does not pass through the elongated shaft. Furthermore, the extension cannula may include an in-line connector coupled between the ECMO machine and the ECMO return cannula, which may include a side arm with a lumen in fluid communication with the lumen of the elongated shaft. Thus, the extension cannula may be advanced over the guidewire to a 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 a conventional ECMO return cannula or may be incorporated into the conventional ECMO return cannula as a single unit. A stylet may be inserted into the lumen of the side arm of the in-line connector and into the elongated shaft to prevent blood flow therethrough during operation of the ECMO machine. Alternatively, a cap may be configured to removably engage a side arm of the in-line connector and prevent blood flow through the lumen of the elongate shaft during operation of the ECMO machine.

[0026] The proximal end of the flexible conduit may be engaged with the outlet of the ECMO return cannula by an anchoring stent. For example, the anchoring stent may be self-expanding. Thus, a sheath may be removably positioned over the flexible conduit to hold the flexible conduit in a collapsed, inserted state such that upon retraction of the sheath, the flexible conduit is exposed within the patient's vasculature. In some embodiments, the proximal region of the flexible conduit may be fixedly coupled to the ECMO return cannula within the outlet of the ECMO return cannula. For example, the proximal region of the flexible conduit may be configured to be fixedly coupled to the ECMO return cannula via at least one of a heat seal, a two-part polyurethane adhesive, or a segmented polyurethane bond.

[0027] In some embodiments, the extension cannula may further 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 the ECMO circuit such that the first and second branches are in fluid communication with the outlet of the in-line connector, a second branch having a lumen sized and shaped to allow insertion of the extension cannula therethrough, and an outlet sized and shaped to be removably coupled to the ECMO return cannula. In addition, the second branch may be collinear with the outlet of the in-line connector. The in-line connector may be removably coupled to a conventional ECMO return cannula or may be incorporated into the conventional ECMO return cannula as a single unit.

[0028] According to another aspect of the invention, a cannula for use with an ECMO machine is provided. The cannula may include a proximal region having an inlet sized and shaped to be coupled to the ECMO machine, and an outlet sized and shaped to be positioned at a location within the patient's vasculature proximal to the patient's renal vasculature. For example, the cannula may include a conduit formed by a flexible, 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 an expanded, deployed state upon communication with blood flow from the ECMO machine. The cannula may further include an elongated shaft having a distal region coupled to a distal end of the conduit such that the elongated shaft may be used to advance the conduit in the collapsed, insertion state and position the distal end beyond the patient's renal vasculature. Additionally, the length of the conduit may be selected such that when the proximal end is located within the outlet at a location within the patient's vasculature proximal to the patient's renal vasculature, the distal end extends beyond the patient's renal vasculature, and the conduit transitions to an expanded, deployed state in the presence of blood flow from the ECMO machine such that the lumen forms a continuation of the blood flow pathway through the cannula. The flexible conduit may include a distal region having a number of pores sized and shaped to allow blood flow to exit the lumen. Additionally, the proximal end of the conduit may be attached to the outlet by a stent.

[0029] According to yet another aspect of the invention, a cannula extension for use with a conventional ECMO return cannula is provided. The cannula extension includes an elongate shaft having a proximal end and a distal region, and a conduit coupled to the distal region of the elongate shaft. The elongate shaft can be used to position the proximal end in fluid communication with a lumen of the conventional ECMO return cannula such that the distal end of the conduit extends beyond the renal arteries, for example, into the thoracic or abdominal aorta. The shaft can include a proximal end extending through a port near the proximal end of the ECMO return cannula, which can be manipulated by a clinician. The conduit has an inlet, an outlet, an interior lumen extending therebetween, and a diameter configured to transition between a collapsed insertion state and an expanded deployed state. The inner diameter of the conduit may be sized and shaped to receive at least one of a catheter for coronary, peripheral, cerebral, or valvular intervention, a catheter for antegrade limb perfusion, or a catheter for intra-aortic, transvalvular pneumatic, or rotary flow pump delivery.

[0030] In a preferred embodiment, the conduit has a length selected such that when the extension cannula is inserted through the lumen of a 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 within the patient's thoracic aorta, e.g., the descending aorta, the aortic arch, or the ascending aorta. In accordance with the principles of the present invention, as used herein, the patient's thoracic aorta may include a portion of the descending aorta above the level of the diaphragm such that the outlet of the conduit may reside within the descending aorta just below the patient's thoracic cavity approaching the level of the diaphragm. The conduit may include a support structure such as a self-expanding mesh, woven fabric, or braid encapsulated with a flexible biocompatible coating, e.g., ePTFE. Alternatively, the support structure may include a spine or framework made of shape memory alloy, plastic, or stainless steel. As a further alternative, the conduit may take the form of a hollow sock-like structure having one or more pores coupled to a flexible spine or hypotube. For example, multiple pores may be disposed within the lateral surface of the conduit. In this latter embodiment, the sock-like structure expands when filled with blood pumped from the ECMO circuit. For example, the conduit may be formed from a soft, flexible material such that it may transition to the deployed state by blood pumped through the internal lumen by the ECMO system. Multiple pores in the soft, flexible material allow blood to exit the lumen without jetting.

[0031] The extension cannula of the present invention is expected to provide improved delivery of oxygenated blood from the ECMO machine. For example, the conduit may have a length (e.g., 20-80 cm) selected such that when the extension cannula is inserted through the lumen of the ECMO return cannula and, for example, transitioned to an expanded deployed state 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 renal vasculature of the patient, for example, into the aortic arch, and the internal lumen forms a continuation of the blood flow pathway through the internal lumen, delivering blood flow from the ECMO machine beyond the renal vasculature of the patient, for example, to the aortic arch of the patient, thereby reducing cardiac work of the right and left ventricles of the patient. Furthermore, the reduction in cardiac work may reduce left ventricular dysfunction and reduce the long-term effects of cardiac infarction.

[0032] According to yet another aspect of the invention, a single constructed ECMO cannula may be configured to be positioned through the femoral vein, with the inlet of the extension cannula being placed into the patient's pulmonary artery, thereby serving as a cannula that selectively allows blood to be drawn from the pulmonary artery into the ECMO circuit. Using this approach, it may be possible to reduce left ventricular wall stress and distension by reducing flow across the lungs, thereby reducing preload to the left ventricle.

[0033] As yet a further alternative, the outlet of a single constructed extension cannula may be placed in the aortic root or left ventricle of the patient and sized to receive at least one of a catheter for coronary, peripheral, cerebrovascular, or valvular intervention, or a catheter for placement of additional pump technology within the left ventricle, such as a pneumatic or rotary flow pump inside the aorta, e.g., an intra-aortic balloon pump (IABP), or a transvalvular rotary flow pump, e.g., an Impella® pump (marketed by AbioMed, Danvers, Massachusetts).

[0034] According to yet another aspect of the present invention, a single constructed extension cannula for use with an ECMO inlet cannula having an inlet and an outlet is provided. The extension cannula includes an elongate shaft having a proximal end and a distal region, and an expandable conduit coupled to the distal region of the elongate shaft. The conduit has an inlet, an outlet, and an internal lumen and has a diameter that transitions between a collapsed, inserted state and an expanded, deployed state. The conduit has a length selected such that when the extension cannula is inserted through the 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 is within the right ventricle of the patient. For example, the integrally formed cannula and conduit may have a length of 80-100 cm, and the conduit may have a length of 40-70 cm.

[0035] Methods for using the extension cannula of the present invention are also provided. For example, the extension cannula of the present invention can be used to reduce or prevent myocardial damage in a subject caused by acute myocardial infarction, heart failure, cardiac arrest, pulmonary embolism, myocarditis, or pulmonary injury, for example, by reducing left heart load and improving mitochondrial CI function. In addition, the extension cannula of the present invention can be used to reduce myocardial infarction size caused by obstruction of coronary blood flow and limit the development of post-infarction heart failure. Furthermore, the extension cannula of the present invention can be used to increase cardioprotective signaling pathways in the heart during acute myocardial infarction or heart failure, reduce myocardial injury, improve myocardial recovery, enhance the effect of impaired pulmonary function, reduce the incidence and severity of North-South syndrome, and increase antegrade blood flow to the descending aorta and adjacent arteries of a patient, thereby reducing the load of the left ventricle of a patient, reducing cardiac output at lower pressures, and reducing left and right ventricular load.

[0036] According to one aspect of the invention, a kit for use with an ECMO machine is provided. The kit may include a cannula having a proximal region having an inlet configured to be coupled to an ECMO machine and an outlet configured to be positioned at a location within the patient's vasculature proximal to the patient's renal vasculature, and a cannula extension. The cannula extension 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 an expanded, deployed state when the lumen is in communication with blood flow from the ECMO machine such that the lumen forms a continuation of the blood flow pathway through the cannula. The cannula extension may further include an elongate shaft having a distal region coupled to a distal end of the flexible conduit. The elongate shaft may be configured to advance the flexible conduit in the collapsed, insertion state to position the distal end beyond the patient's renal vasculature. The kit may further include a peelable introducer disposed over at least a portion of the flexible conduit. The peelable introducer may be retracted proximally relative to the flexible conduit and peeled away from the flexible conduit. Further, the length of the flexible conduit may be selected such that the distal end extends beyond the patient's renal vasculature when the proximal end is located within the outlet at a location within the patient's vasculature proximal to the patient's renal vasculature.

[0037] The peelable introducer may have a diameter equal to a diameter of the cannula at most. In some embodiments, the peelable introducer may extend along the entire length of the flexible conduit. The elongate shaft may extend proximally from the distal end of the flexible conduit along a side of the flexible conduit. For example, the elongate shaft may extend along an inner surface of the flexible conduit, along an outer surface of the flexible conduit, or may be embedded within the membrane of the flexible conduit. Alternatively, the elongate shaft may extend proximally within the lumen from the distal end of the flexible conduit along the longitudinal axis of the flexible conduit. For example, the elongate shaft may extend along a central portion of the lumen. Alternatively, at least a portion of the elongate shaft may be embedded within the membrane of the flexible conduit such that at least a portion of the elongate shaft may extend proximally within the flexible conduit from the distal end of the flexible conduit. The elongate shaft may be configured such that a blood flow pathway does not pass through the elongate shaft. Additionally, the elongate shaft may include a hypotube providing a lumen configured to receive a guidewire therethrough.

[0038] The cannula extension may further include a support coupled to a distal region of the flexible conduit. The support may extend circumferentially along the flexible conduit and transition from a collapsed delivery state to an expanded deployed state. In addition, the cannula extension may include a plurality of connecting structures extending between a distal end of the flexible conduit and the support. The plurality of connecting structures may transition from a collapsed delivery state to an expanded deployed state. The distal end of the elongate shaft may include an atraumatic tip configured to be coupled to the support via a plurality of connecting structures. In some embodiments, the atraumatic tip may include one or more holes extending therethrough, the one or more holes sized and shaped to allow blood flow therethrough to mitigate formation of blood clots adjacent the tip within the flexible conduit. The flexible conduit may include at least one of polyethylene, polyurethane, or nylon.

[0039] Additionally, the outlet of the flexible conduit may include one or more pores disposed at a distal region of the flexible conduit. Additionally, the distal portion of the flexible conduit may include a tapered portion having a cross-sectional area that decreases toward the distal end of the flexible conduit such that the outlet of the flexible conduit includes one or more effluent holes disposed at least on the tapered portion of the flexible conduit. The one or more effluent holes may be disposed circumferentially around the tapered portion of the flexible conduit and may extend longitudinally along the tapered portion. Additionally, the width of the one or more effluent holes 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. For example, the proximal end of the flexible conduit may be configured to be fixedly coupled to the cannula via at least one of a heat seal, a two-part polyurethane adhesive, or a sectioned polyurethane bond. In some embodiments, 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 of 80-100cm, and the flexible conduit may have a length of 40-70cm.

[0040] The kit may further 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. Thus, the kit may further include a console operably coupled to the one or more sensors, the console configured to display measurements of the one or more sensors. Additionally, the elongate 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.

[0041] According to another aspect of the present invention, a method of improving systemic perfusion is provided, comprising: advancing a distal end of a flexible extension cannula within a patient's vascular system via an elongate shaft coupled to a distal end of the flexible extension cannula, a proximal region of the flexible extension cannula being 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 being disposed within a peelable introducer; positioning the peelable introducer within the patient's vascular system such that the proximal end of the peelable introducer remains external to the patient and the distal end of the flexible extension cannula is positioned within the patient's vascular system; retracting the peelable introducer relative to the flexible extension cannula to remove the peelable introducer. and advancing the ECMO return cannula into the patient's vascular system such that the flexible extension cannula extends from a location proximal to the patient's renal vasculature to a location beyond the patient's renal vasculature; transitioning the flexible extension cannula from a collapsed insertion state to an expanded deployed state upon communication with blood flow from the ECMO machine, the flexible extension cannula having a lumen in the expanded state; and delivering blood flow through the lumen of the flexible extension cannula via a plurality of pores disposed in a distal region of the flexible extension cannula to a location beyond the patient's renal vasculature, thereby improving systemic perfusion. 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 the collapsed delivery state to the expanded deployed state, and optionally transitioning a plurality of connecting structures extending from a distal end of the flexible extension cannula to the support from the collapsed delivery state to the expanded deployed state. [Brief description of the drawings]

[0042] [Figure 1A] 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 the delivery sheath removed.

[0043] [Figure 1B] FIG. 1B is a side view of the cannula extension of FIG. 1A, with the extension conduit in a retracted state within the delivery sheath.

[0044] [Diagram 2] 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.

[0045] [Figure 3A] FIG. 3A is a schematic diagram of an exemplary in-line connector configured for use with the cannula extension of the present invention.

[0046] [Figure 3B] FIG. 3B illustrates an end cap for use with the in-line connector of FIG. 3A.

[0047] [Figure 4-1] 4A-4C are schematic diagrams illustrating the use of an exemplary in-line connector with the extension cannula of FIG. 1A in an ECMO system.

[0048] [Figure 4-2] FIG. 4D is a schematic diagram illustrating the use of an exemplary in-line connector with an alternative exemplary extension cannula in an ECMO system.

[0049] [Diagram 5] FIG. 5 is a flow chart of illustrative steps for improving perfusion during ECMO in accordance with the principles of the present invention.

[0050] [Figure 6-1] 6A-6E illustrate exemplary steps for improving perfusion during ECMO using the extension cannula of the present invention. [Figure 6-2] 6A-6E illustrate exemplary steps for improving perfusion during ECMO using the extension cannula of the present invention. [Figure 6-3]6A-6E illustrate exemplary steps for improving perfusion during ECMO using the extension cannula of the present invention.

[0051] [Figure 7A] FIG. 7A 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.

[0052] [Figure 7B] FIG. 7B is a side view of the cannula extension of FIG. 7A in an expanded state.

[0053] [Figure 8-1] 8A-8C are schematic diagrams illustrating the use of an exemplary in-line connector with the extension cannula of FIGS. 7A and 7B in an ECMO system.

[0054] [Figure 8-2] FIG. 8D is a schematic diagram illustrating the use of the extension cannula of FIGS. 7A and 7B in an ECMO system.

[0055] [Figure 9] 9A and 9B illustrate exemplary steps for improving perfusion during ECMO using the extension cannula and exemplary in-line connector of FIGS. 7A and 7B.

[0056] [Figure 10] 10A and 10B illustrate exemplary steps for improving perfusion during ECMO using the extension cannula of FIGS. 7A and 7B.

[0057] [Figure 11-1] FIG. 11A is a schematic diagram illustrating the 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 the proximal end of the extension cannula is coupled to a conventional ECMO cannula.

[0058] [Figure 11-2] FIG. 11B is a schematic diagram illustrating the use of the extension cannula of FIG. 11A in an ECMO system without an in-line connector.

[0059] [Figure 11-3] FIG. 11C is a schematic diagram illustrating the use of an exemplary connector having a side arm with an extension cannula of FIG. 11A in an ECMO system.

[0060] [Figure 11-4] 11D-11F are cross-sectional views of the cannula extension of FIG. 11B.

[0061] [Figure 12] FIG. 12 is a flow chart of illustrative steps for improving perfusion during ECMO using the extension cannula of FIGS. 11A-11C in accordance with the principles of the present invention.

[0062] [Figure 13] 13A and 13B illustrate exemplary steps for improving perfusion during ECMO using the extension cannula of FIG. 11A.

[0063] [Figure 14] 14A and 14B illustrate exemplary steps for improving perfusion during ECMO using the extension cannula of FIG. 11B.

[0064] [Figure 15] 15A and 15B illustrate exemplary steps for improving perfusion during ECMO using the extension cannula of FIG. 11C.

[0065] [Figure 16] FIG. 16 illustrates an alternative exemplary cannula extension in an ECMO system having one or more sensors constructed in accordance with the principles of the present invention, where the proximal end of the cannula extension is coupled to a conventional ECMO cannula.

[0066] [Figure 17-1] 17A and 17B are schematic diagrams illustrating the cannula extension of FIG. 11B with a peelable introducer constructed in accordance with the principles of the present invention.

[0067] [Figure 17-2] FIG. 17C is a schematic diagram illustrating the cannula extension of FIG. 11C with a peelable introducer constructed in accordance with the principles of the present invention.

[0068] [Figure 18] FIG. 18 is a flow chart of illustrative steps for improving perfusion during ECMO using the extension cannula of FIGS. 17A-17C in accordance with the principles of the present invention.

[0069] [Figure 19-1] 19A-19D illustrate exemplary steps for improving perfusion during ECMO using the extension cannula of FIG. 11B. [Figure 19-2] 19A-19D illustrate exemplary steps for improving perfusion during ECMO using the extension cannula of FIG. 11B.

[0070] [Figure 20-1] 20A and 20B illustrate an alternative cannula extension having a lateral hypotube constructed in accordance with the principles of the present invention.

[0071] [Figure 20-2] FIG. 20C is a cross-sectional view of the cannula extension of FIG. 20A.

[0072] [Figure 21-1] 21A and 21B illustrate an alternative cannula extension having a central hypotube constructed in accordance with the principles of the present invention.

[0073] [Figure 21-2] FIG. 21C is a cross-sectional view of the cannula extension of FIG. 21A.

[0074] [Figure 22] 22A-22C illustrate various configurations of multiple pores in a cannula extension in accordance with the principles of the present invention.

[0075] [Figure 23A] FIG. 23A illustrates the distal end of an alternative cannula extension having a lateral hypotube constructed in accordance with the principles of the present invention.

[0076] [Figure 23B] FIG. 23B illustrates the distal end of an alternative cannula extension having a central hypotube constructed in accordance with the principles of the present invention.

[0077] [Figure 24] FIG. 24 is a graph illustrating VA-ECMO stroke risk.

[0078] [Diagram 25] FIG. 25 depicts North-South syndrome in a patient on ECMO.

[0079] [Figure 26] FIG. 26 is a series of graphs illustrating various parameters for standard conventional ECMO cannulation compared to that achieved using an alternative cannulation in accordance with the principles of the present invention (delivery of blood to the thoracic aorta).

[0080] [Figure 27] FIG. 27 is a series of graphs illustrating various parameters resulting from standard conventional ECMO cannulation, an Impella pump, and the use of an exemplary system of the present invention.

[0081] [Figure 28] FIG. 28 is a series of graphs depicting renal artery blood velocities obtained for standard conventional ECMO cannulation and an exemplary alternative (irrigation) cannulation system of the present invention.

[0082] [Figure 29] FIG. 29 is a graph illustrating renal artery pulsatility and renal artery microvascular resistance for standard conventional ECMO cannulation and an exemplary alternative cannulation system of the present invention.

[0083] [Diagram 30] FIG. 30 is a graph showing urinary levels of kidney-damaging molecules associated with standard conventional ECMO cannulation and the use of an exemplary alternative cannulation system of the present invention.

[0084] [Figure 31A] FIG. 31A illustrates left and right ventricular responses during conventional ECMO cannulation.

[0085] [Figure 31B] FIG. 31B illustrates left and right ventricular response during ECMO using the extension cannula of the present invention.

[0086] [Diagram 32] FIG. 32 is a graph illustrating pressure volume area (PVA), stroke work (SW), and end diastolic pressure (EDP) associated with standard conventional ECMO cannulation and the use of an exemplary alternative cannulation system of the present invention.

[0087] [Figure 33A] FIG. 33A illustrates infarct size associated with standard conventional ECMO cannulation and the use of an exemplary alternative cannulation system of the present invention.

[0088] [Figure 33B] FIG. 33B is a graph showing standard ischemia-reperfusion injury (IRI) and infarct size associated with standard conventional ECMO cannulation and with the use of an exemplary alternative cannulation system of the present invention.

[0089] [Diagram 34] FIG. 34 is a graph illustrating standard ischemia reperfusion injury (IRI) and oxygen consumption rate (OCR) associated with standard conventional ECMO cannulation with and without an impeller and with the use of an exemplary alternative cannulation system of the present invention.

[0090] [Diagram 35] FIG. 35 is a graph illustrating standard ischemia-reperfusion injury (IRI) on mitochondrial complex I (CI) function and oxygen consumption rate (OCR) associated with standard conventional ECMO cannulation with and without an impeller and with the use of an exemplary alternative cannulation system of the present invention.

[0091] [Figure 36A] FIG. 36A illustrates an extension cannula in an ECMO system constructed in accordance with the principles of the present invention, where the distal end of the extension cannula is positioned in the pulmonary artery and the proximal end of the extension cannula is coupled to a conventional ECMO cannula via the femoral vein.

[0092] [Figure 36B] FIG. 36B illustrates an extension cannula in an ECMO system constructed in accordance with the principles of the present invention, where the distal end of the extension cannula is positioned in the pulmonary artery and the proximal end of the extension cannula is coupled to a conventional ECMO cannula via the internal jugular vein. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0093] Systems and methods are provided for use with ECMO systems to increase blood flow to the thoracic aorta, ascending aorta, and aortic arch, thereby promoting normal antegrade flow to the carotid arteries 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 may also improve the incidence of North-South syndrome in patients with compromised pulmonary function, thereby ensuring proper flow of oxygenated blood to the patient's cerebral vasculature.

[0094] 1A, a cannula extension 10 suitable for use with a conventional VA-ECMO cannula is described. The cannula extension 10 may be constructed as described in U.S. Pat. Nos. 11,331,421 and 11,547,786, the entire contents of each of which are incorporated herein by reference. For example, the cannula extension 10 may include a shaft 17 extending between a distal region 11 and a proximal region 13 of the cannula extension 10. The shaft 17 is formed from a material (e.g., a stainless steel rod) having sufficient rigidity to allow the cannula 10 to be advanced through a conventional ECMO reperfusion cannula, such that the distal region 11 of the self-expanding conduit 12 may be positioned with its outlet extending beyond the patient's renal arteries (preferably extending into the patient's ascending aorta or proximal to the aortic arch). The self-expanding conduit 12 may optionally include a handle 15 coupled to a shaft 17 at the proximal region 13 of the self-expanding conduit 12 for steering the cannula extension 10 .

[0095] The self-expanding conduit 12 has an inlet 16 at its proximal end, an outlet 14 at its distal end, and a lumen extending therethrough to permit blood flow. The self-expanding conduit 12 has a length sufficient to extend, for example, 15-120 cm, or preferably 20-80 cm, from the outlet of a conventional VA-ECMO cannula to a location above the patient's renal arteries, and more preferably into the thoracic aorta. As described more fully below, the self-expanding conduit 12 includes a self-expanding support structure, such as a mesh, fabric, or braid, covered by a flexible and biocompatible covering. Additionally, as shown in FIG. 1A, the self-expanding conduit 12 may include one or more radiopaque markers 18, which are positioned along the distal end of the self-expanding conduit 12 adjacent the outlet 14 to allow its location to be determined fluoroscopically. Additionally, the biocompatible covering proximate the distal end of the self-expanding conduit 12 may be omitted, allowing blood to exit laterally therethrough and perfuse into the thoracic aorta.

[0096] The support structure of the self-expanding conduit 12 may be made from a wire mesh, weave, or braid formed from a shape memory metal or stainless steel such that the self-expanding conduit 12 may transition from a collapsed insertion state to an expanded deployed state. As depicted in FIG. 1B, the support structure of the conduit may be formed from a stainless steel mesh, weave, or braid having a pre-set expanded diameter that forms a central lumen, whereby the conduit may be contracted when pulled into a smaller diameter delivery sheath 40. Alternatively, the support structure may be a mesh, weave, or braid formed from a shape memory metal such as a nickel titanium alloy ("nitinol"), having a pre-set expanded diameter that forms an internal lumen. In this manner, the conduit may be contracted to a collapsed insertion state when pulled into a delivery sheath 40, as described in more detail below.

[0097] The support structure is preferably encapsulated with a biocompatible polymer coating, such as expanded polytetrafluoroethylene ("ePTFE"). In the expanded deployed state, the self-expanding conduit 12 assumes a diameter that is substantially the same as, or even larger than, the inner lumen of a conventional VA-ECMO cannula, and thus does not require a larger caliber opening in the femoral vasculature. For example, the width of the self-expanding conduit 12 may range from 14 French to 40 French in the expanded state. When inserted through a conventional ECMO cannula, the self-expanding conduit 12 allows increased blood flow to the ascending aorta and aortic arch while maintaining the diameter of the vascular opening in the femoral artery required to introduce a conventional VA-ECMO return cannula. In some embodiments, the biocompatible polymer coating may include pores that allow blood to perfuse laterally through the material, thereby reducing spraying from the outlet 14.

[0098] Still referring to FIG. 1A, in one preferred embodiment, the inlet 16 at the proximal end of the self-expanding conduit 12 may have features to facilitate recapture of the self-expanding conduit 12 into the delivery sheath. For example, as shown in FIG. 1A, the self-expanding conduit 12 may have a tapered geometry 19 that facilitates retrieval of the self-expanding conduit 12. For example, the support structure of the self-expanding conduit 12 may include a laterally displaced wire hoop that resides along the edge of the inlet 16, thereby forming the tapered geometry 19. Alternatively, the distal end of the shaft 17 may be coupled to a support leg that is coupled to the proximal end of the support structure of the self-expanding conduit 12, such that advancing the sheath over the support leg causes the support structure of the self-expanding conduit 12 to fold inwardly into a folded insertion state, as described in more detail below. Additionally, the distal end of the self-expanding conduit 12 may include an atraumatic region.

[0099] 2, an alternative embodiment of the extension cannula 10' of the present invention is described. In this embodiment, the conduit 12' is made of a soft, flexible material such as polyethylene, polyurethane, or nylon, and the conduit 12' may include pores that allow some blood to perfuse laterally through the material while directing the majority of the flow through the conduit 12' to the outlet 14'. The elongated shaft 17' serves as a spine to aid in threading the extension conduit 12' into the lumen of a conventional ECMO cannula, positioning the inlet 16' near the outlet of the ECMO cannula and the outlet 14' above the patient's renal arteries, and more preferably in the distal region 11' that extends into the patient's thoracic aorta. The shaft 17' may be coupled to a handle 15' for steering the device 10'. The conduit 12' preferably includes a self-expanding assist hoop 19' at its proximal end that expands the opening 16' at the proximal end of the conduit 12' upon release from the delivery sheath, as described above with respect to FIG. 1B. The conduit 12' may include a radiopaque marker 18' near the outlet 14'. The assist hoop 19' ensures that blood flow through a conventional ECMO cannula is funneled into the proximal end of the conduit 12', causing the remainder of the conduit 12' to be fully open. With respect to the embodiment of FIG. 1A, the conduit 12' may be collapsed upon completion of the reperfusion procedure by advancing the sheath 40 distally over the elongate shaft 17' and the conduit 12'.

[0100] With reference to Figure 3A, an in-line connector 20 suitable for use with the extension cannula of the present invention is described. The in-line connector 20 has a first branch inlet 22 configured to be coupled to an outlet of a conventional ECMO machine to receive oxygenated blood from an ECMO circuit, a second branch inlet 26 having a hemostasis valve welded therein, and an outlet 24 configured to be coupled to a conventional ECMO cannula. The first branch inlet 22 and the second branch inlet 26 are each in fluid communication with the outlet 24, and each may include an optional hemostasis valve 25, as described below with reference to Figure 3B. The flow path extending between the first branch inlet 22 and the outlet 24 thus allows oxygenated blood received from the ECMO circuit to flow through the conventional ECMO cannula and the self-expanding conduit 12. Additionally, the flow passage extending between the second branch inlet 26 and the outlet 24 is sized and shaped to permit delivery therethrough of the self-expanding conduit 12 in a collapsed insertion state (e.g., when disposed within the delivery sheath 40). Thus, the extension cannula 10 of FIGS. 1A and 1B or the extension cannula 10' of FIG. 2 may be inserted through the hemostatic valve of the second branch inlet 26 and advanced through the lumen of a conventional ECMO return cannula coupled to the outlet 24.

[0101] As will be appreciated by those skilled in the art, the flow path extending between the second branch 26 and the outlet 24 may be sized and shaped to allow for the delivery of other interventional tools therethrough as well, including, for example, catheters for coronary, peripheral, or cerebrovascular or valvular interventions, and / or pneumatic, rotary, or transvalvular flow pumps. The delivery of the extension cannula 10 or 10' and other large-bore interventional devices or small catheters is also possible due to the collinearity of the second branch inlet 26 with the outlet 24. Unlike previously known Y-shaped connectors used in interventional procedures, the linear alignment of the second branch inlet 26 and the outlet 24 of the in-line connector 20 allows the device to be inserted without bending. Thus, the linear alignment of the second branch inlet 26 and the outlet 24 of the in-line connector 20 accommodates the delivery of larger-bore devices, for example, delivery catheters for transcatheter aortic valve replacement (TAVR) valves, Impella pumps, or smaller catheters, such as coronary, cerebral, or peripheral vascular intervention guide catheters.

[0102] The in-line connector 20 may be removably coupled to a conventional ECMO return cannula, for example, by clamping the ECMO return cannula, uncoupling the ECMO return cannula from the ECMO circuit, and coupling the in-line connector 20 to the ECMO circuit and ECMO return cannula via the first branch inlet 22 and outlet 24, respectively, and unclamping the ECMO return cannula, when required for an extension cannula or other interventional device to be delivered. Advantageously, the in-line connector 20 allows for the extension of an existing short ECMO cannula without interrupting ECMO flow, adjustment of the location of the extension cannula within the aorta, and removal of the extension cannula. Alternatively, the in-line connector 20 may be integrally constructed as part of the ECMO return cannula, for example, a 15, 17, 19, 21, or 25 French conventional ECMO return cannula. Thus, the in-line connector 20 may include an end cap coupled to the second branch inlet 26 when no device is delivered therethrough. As described above, the 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 an end cap may be coupled to the second branch inlet 26 to prevent further exposure of the hemostatic valve. Advantageously, the single-construction cannula allows for high velocity delivery of fluid above the renal vasculature without the need for an in-line connector, and also allows for positioning of the extension cannula along the length of the aorta.

[0103] The single-assembly cannula described herein may have a length sufficient to extend from the outlet of the VA-ECMO circuit to a position above the renal arteries of the patient, and more preferably into the thoracic aorta. For example, the single-assembly cannula may have a total length of, for example, 80-100 cm from the proximal end of the single-assembly cannula to the distal tip of the expandable conduit. Further, the single-assembly cannula may have a length of 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 of 40-70 cm.

[0104] An optional side arm 27 coupled to and in fluid communication with the second branch inlet 26 is also shown in FIG. 3A. The side arm 27 may be used for flushing the in-line connector 20 or may be used to fluidly couple the in-line connector 20 to an antegrade perfusion catheter to perfuse the patient's lower extremities and protect against limb ischemia. For example, an antegrade perfusion catheter may be inserted via the side arm 27 through the in-line connector 20 and a conventional ECMO return cannula and positioned within the patient such that oxygenated blood is delivered to the patient's lower extremities.

[0105] In accordance with another aspect of the invention, a variety of end caps and tubing adapters may be provided for use with the second branch inlet 26 of the in-line connector 20. For example, the hemostatic valve 25 may have a diameter, e.g., 3 / 8 inch, sized to selectively close the second branch inlet 26 when not in use. Alternatively, the end cap may include a dual hemostatic valve to prevent backflow of blood through the second branch inlet 26 of the in-line connector 20 when an extension catheter is inserted therethrough, as depicted in FIG. 3B. As a further alternative, the end cap may have a stopper portion having a length extending substantially the length of the lumen of the second branch inlet 26 to prevent blood from pooling within the lumen of the second branch inlet 26.

[0106] 3B, the end cap 34 includes an adapter portion 35 that can be inserted into the outlet tubing of a conventional ECMO system. The end cap 34 preferably includes an internal lumen 36 having a smaller diameter than the lumen of the second branch inlet 26 and suitable for, for example, drug infusion or pressure / flow monitoring. Additionally, the end cap 34 may include a hemostatic valve positioned within the lumen 36 to prevent backflow of blood therethrough. As will be appreciated by those skilled in the art, as an alternative to or in addition to a hemostatic valve, the end cap 34 may include, for example, a screw (opening) valve, a balloon valve, a double membrane valve, etc. Alternatively, the lumen 36 may have a diameter selected depending on the desired procedure. The end cap 34 may be coupled to a second arm of the in-line connector 20 described above, as described above, through which it may allow for delivery of interventional tools and / or removal of an existing ECMO cannula. End cap 34 may be, for example, an in-line connector and / or a screw cap that may be rotatably coupled to an existing ECMO cannula.

[0107] According to another aspect of the invention, the end cap 34 may be incorporated directly into an existing ECMO cannula. For example, instead of using an in-line connector to couple an existing ECMO cannula to an ECMO circuit, the end cap 34 may be coupled directly to the existing ECMO cannula, either as two separate components coupled together or as an integral component, such that the existing ECMO cannula is in fluid communication with the ECMO circuit via the end cap 34. As explained above, the end cap 34 may include one or more hemostatic valves to prevent backflow of blood therethrough. If an existing ECMO cannula needs to be removed and / or replaced, e.g., to replace the existing ECMO cannula for a larger diameter ECMO cannula, the existing ECMO cannula may be removed through the lumen of the end cap 34.

[0108] For example, at the point where an ECMO cannula needs to be removed, clamping may be applied to the ECMO circuit such that it may be decoupled from the end cap 34. A guidewire may then be introduced through the lumen of the end cap 34. The existing ECMO cannula may be removed over the guidewire and a new, larger ECMO cannula, for example a 19 French cannula, may be advanced over the guidewire through the lumen of the end cap 34 and positioned within the patient's vasculature. The ECMO circuit may then be recoupled to the end cap 34 and unclamped, allowing blood to again flow from the ECMO circuit through the new, larger ECMO cannula. Similarly, the ECMO circuit may be decoupled from the end cap 34 in the manner described above when an interventional tool needs to be delivered to the patient, and recoupled once the interventional procedure is completed.

[0109] 4A-4C, the operation of the embodiment of the extension cannula of FIGS. 1A and 1B is depicted diagrammatically in conjunction with the in-line connector 20 of FIG. 3A. First, a conventional ECMO cannula 60 is coupled to the outlet 24 of the in-line connector 20 as shown in FIG. 4A and inserted into the patient's arterial vasculature, for example, via an incision to the femoral artery. An outlet line from the ECMO machine is coupled to the first branch inlet 22. As shown in FIG. 4B, the extension cannula 10 is positioned with the self-expanding conduit 12 in its collapsed, inserted state within the delivery sheath 40 and advanced through the hemostatic valve of the second branch inlet 26 of the in-line connector 20. The extension cannula 10 is positioned such that the distal end of the self-expanding conduit 12 is located in the desired location, e.g., within the thoracic aorta, and the proximal end of the self-expanding conduit 12 is near the distal exit of a conventional ECMO return catheter, as can be determined, e.g., under fluoroscopy, using, e.g., a radiopaque marker band placed on the sheath 40.

[0110] The lumen of the sheath 40 is preferably sized to receive and hold the self-expanding conduit 12 in its collapsed, inserted state. For example, the lumen of the sheath 40 may have a diameter of 1.40 mm to 1.50 mm, more preferably 1.45 mm. The sheath 40 has an outer diameter sized for easy insertion through the lumen of a conventional VA-ECMO return cannula. The sheath 40 is slidably disposed over the self-expanding conduit 12 such that the sheath 40 may be retracted relative to the self-expanding conduit 12, thereby allowing the self-expanding conduit 12 to self-expand from the collapsed, inserted state to the expanded, deployed state.

[0111] 4C, once the sheath 40 and self-expanding conduit 12 are positioned within the desired location as described above, the sheath 40 is retracted while the self-expanding conduit 12 is held in place by the elongated shaft 17 and handle 15, thereby allowing the conduit 12 to transition to its expanded, deployed state. Because the majority of the length of the self-expanding conduit 12 extends beyond the distal end of the conventional ECMO return cannula 60, oxygenated blood from the ECMO machine can be delivered to areas beyond those accessible with the conventional ECMO return cannula. In accordance with one aspect of the present invention, other interventional tools, such as vascular catheters, valve catheters, or intra-aortic or transvalvular pumps, such as the Impella® pump (commercially available from AbioMed, Danvers, Massachusetts), may also be inserted through the ECMO cannula via the second branch inlet 26 of the in-line connector 20 to perform additional interventional procedures simultaneously with VA-ECMO. Additionally, arterial repair tools may be delivered through the in-line connector into the patient's vasculature, for example, to facilitate removal of the arterial cannula. For example, the in-line connector may be used to provide wire re-access to the native femoral vessels, thereby allowing removal of the ECMO cannula and delivery of a vascular closure device upon ECMO decannulation, thereby avoiding the need for surgical repair of the vessels.

[0112] In one preferred embodiment of the extension cannula 10, the self-expanding conduit 12 has a length of 20-80 cm or longer. In this manner, blood can be delivered proximate the patient's thoracic aorta above the ostium of the patient's renal arteries to avoid high flow proximate the patient's renal arteries and reduce the risk of perfusion failure. In addition, when the distal end of the self-expanding conduit 12 is positioned within the ascending aorta, as can be determined under fluoroscopy using the radiopaque marker band 18, the outflow from the self-expanding conduit 12 can also provide oxygenated blood to the cardiac arteries proximate the aortic root and provide antegrade flow to the carotid and downstream arteries.

[0113] Still referring to FIG. 4C, when the patient is to be removed from ECMO, the sheath 40 may be reinserted over the elongated shaft 17 and advanced to collapse and retrieve the self-expanding conduit 12. In this case, the sheath 40 will initially engage the tapered proximal end 19 of the self-expanding conduit 12 such that advancement of the sheath 40 while holding the shaft 17 stationary will cause the self-expanding conduit 12 to collapse inwardly and return to its reduced diameter, collapsed, inserted state. The extension cannula 10 and sheath 40 may then be removed through the hemostatic valve in the second branch inlet 26. The use and operation of the embodiment of FIG. 2 is substantially the same as described above.

[0114] 4D, a further alternative embodiment of an extension cannula and sheath constructed in accordance with the principles of the present invention is described. The self-expanding conduit 12'' may be constructed similarly to the self-expanding conduit 12 of FIG. 4C. For example, the self-expanding conduit 12'' has an inlet 16'', an outlet 14'', and one or more radiopaque marker bands 18'' that correspond to the inlet 16, outlet 14, and bands 18, respectively, of the self-expanding conduit 12. The self-expanding conduit 12'' differs from the self-expanding conduit 12 in that instead of a tapered inlet geometry 19, the self-expanding conduit 12'' has a plurality of angled legs 41 that couple the self-expanding conduit 12'' to an elongated shaft 17'' and facilitate re-sheathment for removal. Preferably, the angled legs 41 are flexible and of uniform length such that when the distal end of the sheath 40 is advanced over the angled legs 41, the legs bend inwardly and the support structure of the self-expanding conduit 12'' folds inwardly.

[0115] Additionally, the sheath 40 may have a rapid exchange configuration, where the sheath 40 has a length appropriate to cover the entire length of the self-expanding conduit 12, 12'', but is joined to a support shaft and a handle is coupled to the end of the support shaft. In this manner, the sheath 40 may be back-loaded over the proximal end of the elongate shaft 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 the shaft 17.

[0116] Still referring to FIG. 4D, the operation of the alternative embodiment of the extension cannula is similar to that of the embodiment of FIGS. 4A-4C. As shown in FIG. 4D, the self-expanding conduit 12″ and sheath 40 are advanced through the in-line connector 20 (see FIG. 4B) and into the lumen of the conventional ECMO return cannula 60, with the self-expanding conduit 12″ in a collapsed, inserted state within the sheath 40. The sheath 40 is withdrawn proximally, as shown in FIG. 4D, while the self-expanding conduit 12″ is held stationary using the elongated shaft 17″, thereby allowing the self-expanding conduit 12″ to self-expand to its predetermined diameter. When the sheath 40 is fully withdrawn, blood flow through the conventional ECMO return catheter 60 is directed through the angled legs 41 to the outlet of the self-expanding conduit 12″, which flexes outward as the support structure of the self-expanding conduit 12″ self-expands. Once the ECMO procedure is completed, blood flow from the ECMO machine is halted. The sheath 40 is then backloaded over the elongated shaft 17'' of the extension cannula as described above and advanced distally using the support shaft of the sheath 40. When the distal end of the sheath 40 contacts the angled legs 41, it flexes the legs inwardly, transitioning the proximal end of the support structure of the self-expanding conduit 12'' to its insertion diameter. Further distal advancement of the sheath 40 thus transitions the remaining length of the self-expanding conduit 12'' to its collapsed insertion state, thereby facilitating removal of the extension cannula.

[0117] Referring now to FIG. 5, a flow chart of exemplary steps for improving perfusion during ECMO according to the principles of the present invention is provided. Some of the steps of the method 50 may be further detailed by reference to FIGS. 6A-6E. For example, FIG. 6A illustrates a conventional ECMO cannula 60 inserted through a patient's femoral artery FA coupled to an ECMO machine 61 via the outlet 24 and first inlet 22 of the in-line connector 20, as described above. As shown in FIG. 6B, a guidewire 62 may be inserted through the second branch inlet 26 and outlet 24 of the in-line connector 20 and through the ECMO cannula 60 until the distal end of the guidewire 62 is advanced to a desired location within the patient's vasculature, e.g., the thoracic aorta TA, such as within the ascending aorta or adjacent the aortic arch.

[0118] In step 51, the distal end of the sheath 40 (having the self-expanding conduit 12 disposed therein in a collapsed, inserted state) is advanced through the ECMO cannula 60, e.g., over a guidewire 62 and via the in-line connector 20. The distal end of the sheath 40 is advanced until positioned at a desired central location within the patient's vasculature, in step 52, as shown in FIG. 6C. In step 53, the sheath 40 is retracted relative to the self-expanding conduit 12 slidably disposed within the lumen of the sheath 40, while the self-expanding conduit 12 remains stationary, transitioning the self-expanding conduit 12 from the collapsed, inserted state to an expanded, deployed state, as shown in FIGS. FIG. 6D illustrates the self-expanding conduit 12 partially and completely expanded within the patient's vasculature, and FIG. 6E illustrates the self-expanding conduit 12 fully expanded within the patient's vasculature, for example, when the self-expanding conduit 12 is fully exposed from the sheath 40. Thus, in step 54, oxygenated blood can be perfused from the ECMO cannula 60 into the patient's vasculature, for example, into the ascending aorta or into a central location proximate the aortic arch. As a result, blood flow into adjacent vessels, for example, the coronary and / or carotid arteries, will occur with a more normal antegrade flow pattern. As will be understood by one skilled in the art, the outlet of the self-expanding conduit 12 can be located within the descending aorta, for example, the portion of the descending aorta approaching the level of the diaphragm from just below the thoracic cavity or the portion of the descending aorta above the diaphragm.

[0119] In accordance with one aspect of the present invention, the ECMO pump may be programmed to generate pulsatile flow, creating pressure fluctuations at the outlet of the self-expanding conduit 12 that mimic the patient's heartbeat. As a result, the patient may receive significant benefits, such as maintaining arterial elasticity and reducing arteriosclerosis, as opposed to continuous flow. Once ECMO therapy is complete, in step 55, the self-expanding conduit 12 may be returned to its collapsed, inserted state within the lumen of the sheath 40, as described above, and in step 56, the sheath 40 and the self-expanding conduit 12 disposed therein may be removed from the patient.

[0120] 7A and 7B, an alternative exemplary extension cannula suitable for use with a conventional VA-ECMO cannula is described. The extension cannula 70 may be constructed as described in U.S. Pat. No. 11,547,786 and U.S. Patent Application No. 18 / 151,982, the entire contents of each of which are incorporated herein by reference. For example, the extension cannula 70 may include an elongated shaft 77, e.g., a hypotube, extending between a distal region 71 and a proximal region 73 of the extension cannula 70. The hypotube 77 is formed from a material, e.g., a stainless steel rod, having sufficient rigidity to allow the extension cannula 70 to be advanced through a conventional ECMO reperfusion cannula, such that the distal region 71 of the expandable conduit 72 may be positioned with its outlet extending beyond the patient's renal arteries, preferably within the patient's ascending aorta or proximal to the aortic arch. For example, the hypotube 77 may have a lumen sized and shaped to receive a guidewire therethrough, such that the cannula extension 70 may be advanced through a conventional ECMO reperfusion cannula, over the guidewire, and through the lumen of the hypotube 77 to the target location. In some embodiments, the hypotube 77 may include an anti-thrombolytic coating. The cannula extension 70 may optionally include a handle 75 for steering the cannula extension 70 coupled to the hypotube 77 at the proximal region 73 of the cannula extension 70.

[0121] The distal end of the hypotube 77 may include an atraumatic tip 78, which may be coupled to a distal region of the expandable conduit 72 via a connecting structure 79 (e.g., one or more umbrella struts). The connecting structure 79 may be self-expandable, for example, between a collapsed delivery state and an expanded deployed state upon exposure from the sheath 40. As shown in FIGS. 7A and 7B, the connecting structure 79 may have a curved shape in the expanded deployed state. The connecting structure 79 may be embedded within a biocompatible material forming the expansion conduit 72. Additionally or alternatively, the connecting structure 79 may be coupled to an inner surface of the expandable conduit 72, an outer surface of the expandable conduit 72, or both. The hypotube 77 does not form part of a blood flow path through the lumen of the expandable conduit 72. In one embodiment, the connecting structure 79 is not self-expandable such that when blood flows through the lumen of the expandable conduit 72, the connecting structure 79 transitions from a collapsed delivery state to an expanded deployed state, thereby causing the expandable conduit 72 to fill with blood.

[0122] The expandable conduit 72 is made from a soft, flexible material such as polyethylene, polyurethane, or nylon, and may include pores 74 at its distal region that allow blood to perfuse through the material when flow is directed through the lumen of the expandable conduit 72. For example, the expandable conduit 72 has an inlet 76 at its proximal end and an outlet (e.g., multiple pores 74) at its distal region to allow blood flow, and a lumen extending through the expandable conduit 72. The pores 74 may be sized and shaped to cause the expandable conduit 72 to fill with blood and transition from a collapsed delivery state as shown in FIG. 7A to an expanded deployed state as shown in FIG. 7B, while blood flow exits the expandable conduit 72 through the pores 74 as blood flows from the ECMO machine, through a conventional ECMO reperfusion cannula, and through the lumen of the expandable conduit 72. Additionally, the expandable conduit 72 has a sufficient length, e.g., 15-120 cm, or preferably 20-80 cm, or 30-50 cm, to extend from the exit of a conventional ECMO reperfusion cannula to a location above the patient's renal arteries, and more preferably into the thoracic aorta. Notably, the lightweight sock-like structure provides advantages including ease of deployment, for example, through a tortuous or diseased aorta, as well as the absence of any impingement on the spinal cord, as the use of a stiff cannula may impinge on the spinal cord when most patients are lying flat.

[0123] In addition, the expandable conduit 72 may include a self-expanding support structure, such as an anchoring stent 80, such as a mesh, fabric, or braid formed from a shape memory metal or stainless steel at its proximal end, such that the anchoring stent 80 may transition from a collapsed insertion state within the lumen of a conventional ECMO reperfusion cannula to an expanded deployed state, thereby anchoring the expandable conduit 72 within the conventional ECMO reperfusion cannula. For example, the anchoring stent 80 may be biased toward an expandable deployed state such that the anchoring stent 80 may self-expand upon exposure from the sheath 40. The anchoring stent 80 may be covered by a flexible and biocompatible covering, or alternatively, the anchoring stent 80 may be uncovered. The anchoring stent 80 may be formed from a stainless steel mesh, fabric, or braid having a preset expanded diameter that forms a central lumen such that the expandable conduit 72 may be contracted as it is pulled within the smaller diameter delivery sheath 40. Alternatively, the anchoring stent 80 may be a mesh, weave, or braid formed from a shape memory metal, such as a nickel-titanium alloy ("Nitinol"), and has a predetermined expanded diameter that defines an internal lumen. In this manner, the expandable conduit 72 may be contracted to a collapsed, insertion state when pulled within the delivery sheath 40, as described in more detail below.

[0124] In a fully expanded deployed state, the anchoring stent 80 assumes a diameter that is substantially the same as, or even larger than, the inner lumen of a conventional VA-ECMO cannula. For example, the lumen of the anchoring stent 80 may be at least 15 French in the expanded state. Thus, when deployed within the lumen of a conventional ECMO cannula, the anchoring stent 80 will expand to the diameter of the lumen of the conventional ECMO cannula such that the anchoring stent 80 will exert a radially outward force against the inner surface of the conventional ECMO cannula, thereby anchoring the anchoring stent 80 within the lumen of the conventional ECMO cannula. When inserted through a conventional ECMO cannula and anchored to the conventional ECMO cannula via the anchoring stent 80, the expandable conduit 72 allows increased blood flow to the ascending aorta and aortic arch while maintaining the diameter of the vascular opening required for introducing a conventional VA-ECMO return cannula into the femoral artery. In some embodiments, the biocompatible polymer coating may include additional pores proximal to pores 74 that allow blood to perfuse laterally through the material, thereby reducing spraying from pores 74. Like self-expanding conduit 12, expandable conduit 72 may include one or more radiopaque markers disposed along a distal end of expandable conduit 72 adjacent pores 74 that allow the location of the one or more radiopaque markers to be determined fluoroscopically.

[0125] In some embodiments, such as the self-expanding conduit 12'' of FIG. 4D, the inlet 76 at the proximal end of the expandable conduit 72 may have features to facilitate recapture of the expandable conduit 72 within a delivery sheath. For example, the expandable conduit 72 may have multiple angled legs that couple the anchoring stent 80 of the expandable conduit 72 to the shaft 77 and facilitate retraction of the expandable conduit 72 into the sheath for removal. Preferably, the angled legs are flexible and of uniform length, so that when the distal end of the sheath 40 is advanced over the angled legs, the legs bend inwardly, causing the anchoring stent 80 to fold inwardly toward its collapsed delivery state. Alternatively, when the expandable conduit 72 does not have features to facilitate recapture of the expandable conduit 72, the expandable conduit 72 may be removed along with the conventional ECMO cannula by turning off the ECMO machine and stopping blood flow into the expandable conduit 72, thereby causing the expandable conduit 72 to return to a semi-collapsed state. Thus, the expandable conduit 72 and the conventional ECMO cannula may be removed together from the patient's vasculature.

[0126] As explained above, the sheath 40 may have a rapid exchange configuration, where the sheath 40 has a length appropriate to cover the entire length of the expandable conduit 72, but is joined to a support shaft and a handle coupled to the end of the support shaft. In this manner, the sheath 40 may be back-loaded over the proximal end of the shaft 77 of the cannula extension 70 and manipulated using the support shaft via the handle without interfering with the ability to manipulate the proximal end of the shaft 77.

[0127] 8A-8C, the operation of the embodiment of the extension cannula of FIGS. 7A and 7B is depicted diagrammatically in conjunction with the optional in-line connector 20 of FIG. 3A. As described above with respect to FIGS. 4A and 4B, a conventional ECMO cannula 60 may be coupled to the outlet 24 of the in-line connector 20 and inserted into the patient's arterial vasculature, for example, via a cutdown into the femoral artery, as shown in FIG. 8A. An outlet line from the ECMO machine may be coupled to the first branch inlet 22. As shown in FIG. 8B, the extension cannula 70, positioned with the expandable conduit 72 in its collapsed insertion state within the delivery sheath 40, is advanced through the hemostatic valve of the second branch inlet 26 of the in-line connector 20. The extension cannula 70 is positioned such that the distal end of the expandable conduit 72 is disposed within the desired location, e.g., within the thoracic aorta, and the proximal end of the expandable conduit 72 is near the distal exit of a conventional ECMO reperfusion cannula (e.g., as the proximal end of the expandable conduit 72 can be determined, e.g., under fluoroscopy, using a radiopaque marker band disposed on the sheath 40).

[0128] The lumen of the sheath 40 is preferably sized to receive and retain the expandable conduit 72 in its collapsed, inserted state. The sheath 40 is slidably disposed over the expandable conduit 72, and thus the anchoring stent 80 and connecting structure 79, such that the sheath 40 can be retracted relative to the expandable conduit 72, thereby allowing the connecting structure 79 and / or the anchoring stent 80 to transition from a collapsed, delivery state to an expanded, deployed state upon exposure from the sheath 40.

[0129] 8C, once the sheath 40 and expandable conduit 72 are positioned in the desired location, as described above, the sheath 40 is retracted while the expandable conduit 72 is held in place by the hypotube 77 and handle 75, thereby allowing the connecting structure 79 and / or the anchoring stent 80 to transition to their expanded, deployed state. As shown in FIG. 8C, in its expanded, deployed state, the anchoring stent 80 abuts the inner surface of the conventional ECMO reperfusion cannula 60, thereby anchoring the expandable conduit 72 within the conventional ECMO reperfusion cannula 60. Initially, upon retraction of the sheath 40 and expansion of the connecting structure 79 and / or the anchoring stent 80, the portion of the expandable conduit 72 between the connecting structure 79 and the anchoring stent 80 may still be in a semi-collapsed delivery state, as shown in FIG. 7A. The expandable conduit 72 may transition fully to its expanded, deployed state upon fluid communication with blood flow from the ECMO machine through a conventional ECMO reperfusion cannula 60, as shown in Figure 7B. For example, in a fully expanded state, the expandable conduit 72 may have a diameter of 10-20 mm.

[0130] 8C, the majority of the length of expandable conduit 72 extends beyond the distal end of conventional ECMO reperfusion cannula 60 so that oxygenated blood from the ECMO machine may be delivered, for example, via aperture 74, to areas beyond those accessible with conventional ECMO return cannulas. In one preferred embodiment of extension cannula 70, expandable conduit 72 has a length of 15-120 cm, or preferably 20-80 cm, or more. In this manner, blood may be delivered proximate to the patient's thoracic aorta above the ostium of the patient's renal arteries, avoiding high flow proximate to the patient's renal arteries and reducing the risk of perfusion injury. In addition, when the distal end of the expandable conduit 72 is positioned within the ascending aorta, as can be determined under fluoroscopy using radiopaque marker bands placed on the expandable conduit 72, the outflow from the pores 74 of the expandable conduit 72 can provide oxygenated blood to the cardiac arteries proximate the aortic root and can also provide antegrade flow to the carotid and downstream arteries. Thus, the ECMO reperfusion cannula 60 can be shortened, for example, by 5-15 cm, or preferably, 8-10 cm, compared to a conventional ECMO cannula.

[0131] As explained above, when the patient is to be removed from ECMO, the sheath 40 may be reinserted and advanced over the shaft 77 to collapse and retrieve the expandable conduit 72. In this case, the sheath 40 will initially engage the multiple angled legs that connect the anchoring stent 80 of the expandable conduit 72 to the shaft 77, such that advancement of the sheath 40 while holding the shaft 77 stationary will cause the anchoring stent 80, and thus the expandable conduit 72, to collapse inwardly and return to its reduced diameter, i.e., collapsed, insertion state, within the sheath 40. As the sheath 40 is further advanced distally over the expandable conduit 72, it will engage the connecting structure 79 such that the expandable conduit 72 is disposed within the sheath 40, causing it to collapse inwardly and return to its collapsed, insertion state. The cannula extension 70 and sheath 40 may then be removed through the hemostasis valve in the second branch inlet 26 .

[0132] 8D illustrates an extension cannula 70 coupled to a conventional ECMO reperfusion cannula 60 without an in-line connector 20. As explained above, the in-line connector 20 is optional. Thus, the proximal end of the conventional ECMO reperfusion cannula 60 may be directly coupled to the ECMO circuit.

[0133] 9A and 9B, exemplary steps for improving perfusion during ECMO using the cannula extension of FIGs. 7A and 7B are provided. Specifically, method steps 51-56 of FIG. 5 described above may be used to deliver the cannula extension 70 to improve perfusion during ECMO. First, a distal region of the cannula extension 70 may be delivered to a target location within the thoracic aorta in a collapsed insertion state within the sheath 40, as described above with respect to steps 51 and 52 of FIG. 5, and illustrated by FIGs. 6A-6C. For example, a conventional ECMO cannula 60 may be inserted through a patient's femoral artery FA coupled to an ECMO machine 61 via the outlet 24 and first inlet 22 of the in-line connector 20, and a guidewire 62 may be inserted through the second branch inlet 26 and outlet 24 of the in-line connector 20 and through the ECMO cannula 60 until the distal end of the guidewire 62 is advanced to a desired location within the patient's vasculature, e.g., the thoracic aorta TA, such as within the ascending aorta or adjacent the aortic arch. In step 51, the distal end of the sheath 40 (having the expanded conduit 72 in a collapsed, inserted state disposed therein) is advanced through the ECMO cannula 60 (e.g., over the guidewire 62 via the lumen of the hypotube 77) and the in-line connector 20. The distal end of the sheath 40 is advanced in step 52 until it is positioned at a desired central location within the patient's vasculature, as shown in FIG.

[0134] In step 53, the sheath 40 is retracted relative to the expandable conduit 72 slidably disposed within the lumen of the sheath 40, as shown in FIG. 9A, while the expandable conduit 72 remains stationary, transitioning the connecting structure 79, and thus at least a portion of the expandable conduit 72, from a collapsed insertion state to an expanded deployed state upon exposure from the sheath 40. FIG. 9A illustrates the expandable conduit 72 in a semi-expanded state within the patient's vasculature. The sheath 40 is further retracted relative to the expandable conduit 72, transitioning the anchoring stent 80 from a collapsed insertion state to an expanded deployed state upon exposure from the sheath 40 within the ECMO cannula 60, thereby anchoring the expandable conduit 72 to the ECMO cannula 60. FIG. 9B, for example, illustrates the expandable conduit 72 fully expanded within the patient's vasculature when the expandable conduit 72 is fully exposed from the sheath 40 and blood flows from the ECMO machine, through the ECMO cannula 60, and into the lumen of the expandable conduit 72.

[0135] Once the expandable conduit 72 is fully deployed within the patient's vasculature, at step 54, oxygenated blood may be perfused from the ECMO cannula 60 through the pores 74 in the distal region of the expandable conduit 72 to the patient's vasculature, for example, in the ascending aorta or to a central location proximate the aortic arch. As would be understood by one skilled in the art, the pores 74 of the expandable conduit 72 may be positioned within the descending aorta, for example, the portion of the descending aorta approaching the level of the diaphragm from just below the thoracic cavity or the portion of the descending aorta above the diaphragm. Once ECMO therapy is completed, at step 55, the expandable conduit 72 may be returned to a collapsed, inserted state within the lumen of the sheath 40, as described above, and at step 56, the sheath 40 and the expandable conduit 72 disposed therein may be removed from the patient.

[0136] 10A and 10B, exemplary steps for improving perfusion during ECMO using the extension cannula of FIG. 8D are provided. Specifically, method steps 51-56 of FIG. 5 described above may be used to deliver the extension cannula 70 to improve perfusion during ECMO. First, a distal region of the extension cannula 70 may be delivered to a target location within the thoracic aorta in an insertion state folded within the sheath 40, as described above with respect to steps 51 and 52 of FIG. 5. For example, a conventional ECMO cannula 60 may be inserted through the patient's femoral artery FA. Preferably, the conventional ECMO cannula 60 is not yet coupled to the ECMO machine 61 at this stage. Next, a guidewire 62 may be inserted through the ECMO cannula 60 until a distal end of the guidewire 62 is advanced into the patient's vasculature, for example, into the thoracic aorta TA, to a desired location (such as in the ascending aorta or adjacent to the aortic arch). In step 51, the distal end of the sheath 40 having the expandable conduit 72 disposed therein in a collapsed insertion state is advanced through the ECMO cannula 60, for example, over the guidewire 62 and through the lumen of the hypotube 77. The distal end of the sheath 40 is advanced until it is positioned at a desired central location within the patient's vasculature, in step 52, as shown in FIG. 6C. The guidewire 62 may then be removed through the proximal end of the hypotube 77.

[0137] In step 53, the sheath 40 is retracted relative to the expandable conduit 72 slidably disposed within the lumen of the sheath 40, as shown in FIG. 10A, while the expandable conduit 72 remains stationary, transitioning the connecting structure 79, and thus at least a portion of the expandable conduit 72, from a collapsed insertion state to an expanded deployed state upon exposure from the sheath 40. FIG. 10A illustrates the expandable conduit 72 in a semi-expanded state within the patient's vasculature. The sheath 40 is further retracted relative to the expandable conduit 72, transitioning the anchoring stent 80, upon exposure from the sheath 40 within the ECMO cannula 60, from a collapsed insertion state to an expanded deployed state, thereby anchoring the expandable conduit 72 to the ECMO cannula 60. The proximal end of the ECMO cannula 60 may then be coupled to the ECMO machine 61, for example, via tubing.

[0138] 10B illustrates the expandable conduit 72 fully expanded within the patient's vasculature as, for example, the expandable conduit 72 is fully exposed from the sheath 40 and blood flows from the ECMO machine 61, through the ECMO cannula 60, and into the lumen of the expandable conduit 72. As described above, once the expandable conduit 72 is fully deployed within the patient's vasculature, at step 54, oxygenated blood may be perfused from the ECMO cannula 60 through pores 74 in the distal region of the expandable conduit 72 into the patient's vasculature, for example, into the ascending aorta or to a central location proximate the aortic arch. Once ECMO therapy is completed, at step 55, the expandable conduit 72 may be returned to a collapsed, inserted state within the lumen of the sheath 40, as described above, and at step 56, the sheath 40 and the expandable conduit 72 disposed therein may be removed from the patient.

[0139] 11A, another alternative exemplary extension cannula is provided. The extension cannula 70' may be constructed similarly to the extension cannula 70, except that the proximal end of the expandable conduit 72' may be secured to the conventional ECMO reperfusion cannula 60' prior to insertion of the extension cannula 70' into the patient. As shown in FIG. 11A, the proximal end of the expandable conduit 72' may be coupled to the inner surface of the conventional ECMO reperfusion cannula 60' via a coupling mechanism 81, e.g., adhesive. For example, the proximal end of the expandable conduit 72' may be coupled to the inner surface of the conventional ECMO reperfusion cannula 60' via a heat seal, a two-part polyurethane adhesive, and / or a segmented polyurethane bond. Thus, the extension cannula 70', conventional ECMO reperfusion cannula 60', and in-line connector 20 are advanced together into the patient, for example, by guiding the tip 78' of the extension cannula 70' through the hypotube 77' to position the bore 74' of the expandable conduit 72' adjacent to the aortic root, as described in further detail below.

[0140] FIG. 11B illustrates an extension cannula 70' coupled to a conventional ECMO reperfusion cannula 60' without an in-line connector 20. As explained above, the in-line connector 20 is optional. Thus, the proximal end of the conventional ECMO reperfusion cannula 60' may be directly coupled to the ECMO circuit. As shown in FIGS. 11D-11F, the hypotube 77' may be positioned on a single side within the lumen of the expandable conduit 72' and the ECMO cannula 60'. Specifically, FIG. 11D illustrates a cross-sectional view of the extension cannula 70' along line DD in FIG. 11B, FIG. 11E illustrates a cross-sectional view of the extension cannula 70' along line EE in FIG. 11B, and FIG. 11F illustrates a cross-sectional view of the extension cannula 70' along line FF in FIG. 11B. 11D, the hypotube 77' can be positioned against the inner wall of the ECMO cannula 60' in a proximal region of the ECMO cannula 60'. As shown in FIG. 11E, the hypotube 77' can be positioned against the inner wall of the expandable conduit 72' in a distal region of the ECMO cannula 60', for example, adjacent where the expandable conduit 72' is coupled to the ECMO cannula 60' via coupling mechanism 81. As shown in FIG. 11D, the hypotube 77' can be positioned against the inner wall of the expandable conduit 72' throughout the entire length of the expandable conduit 72'. Thus, the hypotube 77' can extend from the tip 78' along the inner surface of the hypotube 77' toward the ECMO cannula 60'.

[0141] 11C, another exemplary connector for use with the extension cannula described herein is provided. Connector 90 may have an inlet 92 configured to be coupled to an outlet of a conventional ECMO machine to receive oxygenated blood from the ECMO circuit, a side arm 93 extending at an angle from the side of connector 90, and an 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. A flow path extending between inlet 92 and outlet 91 thus allows oxygenated blood received from the ECMO circuit to flow through the conventional ECMO cannula and expandable conduit 72''. As shown in FIG. 11C, inlet 92 may be collinear with outlet 91. Additionally, side arm 93 is in fluid communication with the lumen of hypotube 77'', and side arm 93 may also have an optional hemostatic valve welded therein. Thus, the side arm 93 may have a lumen sized and shaped to receive a guidewire therethrough. Additionally, the side arm 93 and hypotube 77'' may be sized and shaped to receive a stylet therein, which may be configured to be inserted through the side arm 93 and hypotube 77'' to preserve and prevent clogging of the lumen of the side arm 93 and hypotube 77'' during operation. Thus, the proximal end of the stylet may be configured to releasably engage the side arm 93 once the stylet is positioned therethrough, thereby securing the stylet within the side arm 93, for example, via a threaded engagement. Additionally, upon removal of the stylet, a guidewire may be reinserted through the side arm 93 and hypotube 77'' for removal of the extension cannula 70''.

[0142] 12, a flow chart of exemplary steps for improving perfusion during ECMO using any one of the extension cannulas of FIGS. 11A-11C is provided. Some of the steps of the method 100 may be further detailed by reference to FIGS. 13A and 13B, and FIGS. 14A-15B, as described in more detail below. As described above, the expandable conduit 72' is coupled to the ECMO cannula 60' prior to insertion of the extension cannula 70' and the ECMO cannula 60' into the patient. Thus, referring to the extension cannula of FIG. 11A, the hypotube 77' may extend proximally from the tip 78' through the lumen of the expandable conduit 72', the lumen of the ECMO cannula 60', the outlet 24 of the in-line connector 20, and the second branch inlet 26 of the in-line connector 20. Additionally, the ECMO cannula 60' is coupled to the ECMO machine 61 via the outlet 24 and the first inlet 22 of the in-line connector 20. First, a guidewire 62 may be inserted through the hypotube 77' such that the guidewire 62 passes through the second branch inlet 26 and outlet 24 of the in-line connector 20, through the ECMO cannula 60', and through the lumen and tip 78' of the expandable conduit 72'. The guidewire 62 may be advanced through an incision in the patient's femoral artery FA until a distal end of the guidewire 62 is advanced to a desired location within the patient's vasculature, for example, the thoracic aorta TA, such as within the ascending aorta or adjacent the aortic arch.

[0143] In step 101, the distal end of the extension cannula 70', e.g., tip 78' of the expandable conduit 72', is advanced over the guidewire 62 through the lumen of the hypotube 77', along with the ECMO cannula 60' and in-line connector 20, as shown in Figure 13A. The extension cannula 70', ECMO cannula 60', and in-line connector 20 are advanced until the expandable conduit 72' is positioned at a desired central location within the patient's vasculature in step 102 and the ECMO cannula 60' is positioned within the patient's femoral artery FA, ​​as shown in Figure 13B. In step 103, oxygenated blood may be perfused from the ECMO machine 61 through the lumen of the expandable conduit 72' via the in-line connector 20 and the ECMO cannula 60', thereby causing the expandable conduit 72' to be fully expanded within the patient's vasculature, for example, into the ascending aorta or to a central location proximate the aortic arch, via pores 74' in a distal region of the expandable conduit 72', as shown in Figure 13B. As will be appreciated by one skilled in the art, the pores 74' of the expandable conduit 72' may be positioned within the descending aorta, for example, the portion of the descending aorta approaching the level of the diaphragm from just below the thoracic cavity or the portion of the descending aorta above the diaphragm. Once ECMO therapy is completed, in step 104, the ECMO machine may be turned off so that blood no longer flows through the expandable conduit 72', thereby causing the expandable conduit 72' to return to its semi-collapsed state, and in step 105, the extension cannula 70' and ECMO cannula 60' may be removed from the patient.

[0144] 14A and 14B, exemplary steps for improving perfusion during ECMO using the extension cannula of FIG. 11B are provided. Specifically, the method steps 101-105 of FIG. 12 described above may be used to deliver the extension cannula 70' to improve perfusion during ECMO without the use of an in-line connector. For example, in step 101, the distal end of the extension cannula 70', e.g., the tip 78' of the expandable conduit 72', is advanced over the guidewire 62 through the lumen of the hypotube 77' along with the ECMO cannula 60, as shown in FIG. 14A. The extension cannula 70' and ECMO cannula 60' are advanced until the expandable conduit 72' is positioned at a desired central location within the patient's vasculature in step 102, and the 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 ′, which may then be coupled to ECMO machine 61 .

[0145] As explained above, in step 103, oxygenated blood may be perfused from the ECMO machine 61 through the lumen of the expandable conduit 72' via the ECMO cannula 60', causing the expandable conduit 72' to be fully expanded within the patient's vasculature, for example, into the ascending aorta or to a central location proximate the aortic arch, via pores 74' in a distal region of the expandable conduit 72', as shown in FIG. 14B. Once ECMO therapy is completed, in step 104, the ECMO machine may be turned off such that blood no longer flows through the expandable conduit 72', thereby causing the expandable conduit 72' to return to a semi-collapsed state, and in step 105, the extension cannula 70' and ECMO cannula 60' may be removed from the patient.

[0146] 15A and 15B, exemplary steps for improving perfusion during ECMO using the extension cannula of FIG. 11C are provided. Specifically, the method steps 101-105 of FIG. 12 described above may be used to deliver an extension cannula 70″ having a connector 90 coupled thereto to improve perfusion during ECMO. For example, in step 101, the distal end of the extension cannula 70″, e.g., the tip 78″ of the expandable conduit 72″, along with the ECMO cannula 60″ and connector 90, are advanced over the guidewire 62 through the lumen of the hypotube 77″, as shown in FIG. The extension cannula 70″ and ECMO cannula 60″ are advanced until the expandable conduit 72″ is positioned at a desired central location within the patient's vasculature in step 102, with the ECMO cannula 60″ positioned within the patient's femoral artery FA such that the guidewire 62 extends out of the side arm 93. The guidewire 62 may then be removed through the side arm 93. A stylet may then be inserted through the side arm 93 and hypotube 77'', for example, until the end of the stylet is adjacent the tip 78'' of the extension cannula 70'', thereby preventing blood from entering and clogging the hypotube 77'' during operation. As explained above, the proximal end of the stylet may be releasably secured to the side arm 93, for example, via a threaded engagement, while the stylet is disposed therein. Alternatively, an end cap may be coupled to the side arm 93. The inlet 92 of the connector 90 may then be coupled to the ECMO machine 61, as shown in FIG. 15B.

[0147] As explained above, in step 103, oxygenated blood may be perfused from the ECMO machine 61 through the lumen of the expandable conduit 72″ via the connector 90 and the ECMO cannula 60″, causing the expandable conduit 72″ to be fully expanded within the patient's vasculature, for example, into the ascending aorta or to a central location proximate the aortic arch, via the pores 74″ in the distal region of the expandable conduit 72″, as shown in FIG. 15B. Once ECMO therapy is completed, in step 104, the ECMO machine may be turned off such that blood no longer flows through the expandable conduit 72″, thereby causing the expandable conduit 72″ to return to a semi-collapsed state. The stylet may then be removed from the side arm 93 and the hypotube 77″, and the guidewire 62 may be reinserted through the side arm 93 and the hypotube 77″. In step 105, the extension cannula 70'' and ECMO cannula 60'' may be removed from the patient, for example, over the guidewire 62. The existing long venous cannula does not have a proximal connection Luer lock, and therefore, if such a long venous cannula were used in an arterial position, it would not provide antegrade perfusion of the leg. In contrast, the existing arterial cannula may include a proximal connection Luer lock, however, such an arterial cannula is shorter than the existing long venous cannula. Thus, the custom constructed extension cannula described herein provides a proximal connection Luer lock on the long arterial cannula.

[0148] 16, another alternative exemplary cannula extension is provided. The cannula extension 70''' may be constructed similarly to the cannula extensions 70, 70', 70'', except that the cannula extension 70''' may include one or more sensors 62 disposed on a distal region of the expandable conduit 72''' for measuring one or more physiological parameters within the patient's vasculature. For example, the sensors 62 may be pressure sensors, flow sensors, and / or oxygen saturation sensors. Thus, in addition to the guidewire / stylet lumen, the hypotube 77''' may have another separate lumen extending therethrough, the other separate lumen sized and shaped to receive electrical wires for coupling the sensor 62 to the console 63, for example, via the side arm 93, to provide pressure and / or oxygen saturation readings.

[0149] 17A and 17B, a delivery system for delivering the extension cannula 70' is provided. As shown in FIGs. 17A and 17B, at least a portion of the expandable conduit 72' may be disposed within a peelable introducer 85. For example, the introducer 85 may extend proximally from the tip 78' of the expandable conduit 72' toward the proximal region of the expandable conduit 72'. Preferably, the introducer 85 extends along only a portion of the expandable conduit 72'. Alternatively, the introducer 85 may extend along the entire length of the expandable conduit 72'. The introducer 85 preferably has a diameter equal to or slightly smaller than that of the ECMO cannula 60' so that when the introducer 85 is inserted through the patient's skin and into the artery, the arterial puncture will be no larger than the ECMO cannula 60' and insertion of the ECMO cannula 60' into the arteriotomy after the peelable introducer is removed will be hemostatic without bleeding. The introducer 85 can be retracted proximally relative to the expandable conduit 72' and peeled away from its proximal end to the exterior of the patient, as shown in FIG. 17B.

[0150] As shown in FIG. 17C, the peelable introducer 85 may also be used to facilitate delivery of the extension cannula 70'' through the patient's skin and into the artery. For example, as shown in FIG. 17C, the introducer 85 may extend proximally from the tip 78'' of the expandable conduit 72'' toward the proximal region of the expandable conduit 72''. Preferably, the introducer 85 extends along only a portion of the expandable conduit 72''. Alternatively, the introducer 85 may extend along the entire length of the expandable conduit 72''. As will be appreciated by one of ordinary skill in the art, the peelable introducer may be used to facilitate delivery of other extension cannulas described herein where the expandable conduit is pre-secured to an ECMO cannula. For example, the introducer 85 may be used to deliver the extension cannulas described herein coupled to an in-line connector 20.

[0151] 18, a flow chart of exemplary steps for improving perfusion during ECMO using the delivery system of any one of FIGS. 17A-17C is provided. Some of the steps of the method 110 may be further detailed by reference to FIGS. 19A-19D, as described in more detail below. As described above, at least a portion of the expandable conduit 72' is disposed within a peelable introducer 85 such that the introducer 85 extends proximally from the tip 78' toward a proximal region of the expandable conduit 72'. First, a guidewire 62 may be advanced through an incision in the patient's femoral artery FA until a distal end of the guidewire 62 is advanced to a desired location within the patient's vasculature, e.g., the thoracic aorta TA, such as within the ascending aorta or adjacent the aortic arch.

[0152] In step 111, the distal end of the extension cannula 70', e.g., the tip 78' of the expandable conduit 72' disposed within the introducer 85, is advanced over the guidewire 62 through the lumen of the hypotube 77' along with the ECMO cannula 60', as shown in FIG. 19A. In step 112, the extension cannula 70', introducer 85, and ECMO cannula 60' are advanced through the patient's skin S and through the femoral artery FA until the introducer 85 is positioned such that the distal end of the expandable conduit 72' is disposed within the artery. The proximal end of the introducer 85 will remain external to the patient. As explained above, the introducer 85 may be positioned over only a portion of the expandable conduit 72', such that when the introducer 85 is inserted as far as possible through the patient's vasculature while its proximal end remains outside the patient, the distal end of the expandable conduit 72' may not yet be positioned within the patient's vasculature at a desired location, e.g., proximate the aortic arch.

[0153] In step 113, the introducer 85 may be retracted proximally relative to the expandable conduit 72' while the expandable conduit 72' remains stationary within the patient's vasculature. As the introducer 85 is retracted, it may simultaneously be peeled away from the expandable conduit 72' along its proximal end, as shown in FIG. 19B, until the introducer 85 is completely removed from the expandable conduit 72' as shown in FIG. 19C. Once the introducer 85 is completely removed from the expandable conduit 72', in step 114, the extension cannula may be inserted further into the patient until the distal end of the expandable conduit 72' is positioned at a desired central location within the patient's vasculature and the 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 ′, which may then be coupled to ECMO machine 61 .

[0154] In step 115, oxygenated blood is perfused from ECMO machine 61, via ECMO cannula 60', through the lumen of expandable conduit 72', thereby expanding expandable conduit 72' completely within the patient's vasculature, for example, into the ascending aorta or to a central location proximate the aortic arch, as shown in Figure 19D, through pores 74' in a distal region of expandable conduit 72'. As will be appreciated by one skilled in the art, pores 74' of expandable conduit 72' may be positioned within the descending aorta, for example, the portion of the descending aorta approaching the level of the diaphragm from just below the thoracic cavity or the portion of the descending aorta above the diaphragm. Once ECMO therapy is completed, in step 116, the ECMO machine may be turned off so that blood no longer flows through the expandable conduit 72', thereby causing the expandable conduit 72' to return to its semi-collapsed state, and in step 117, the extension cannula 70' and ECMO cannula 60' may be removed from the patient.

[0155] As explained above, in some embodiments, the introducer 85 can extend along the entire length of the expandable conduit 72'. Thus, once the introducer 85 has been inserted as far as possible through the patient's vasculature while its proximal end remains external to the patient, the distal end of the expandable conduit 72' can be positioned within the patient's vasculature at a desired location, for example, within a location proximate the aortic arch, such that upon removal of the introducer 85 from the expandable conduit 72', the extension cannula only needs to be inserted further into the patient until the ECMO cannula 50' is positioned within the patient's femoral artery FA.

[0156] 20A, an additional alternative cannula extension is provided. As shown in FIG. 20A, the cannula extension 120 may include an expandable conduit 122 and an elongated shaft 123, e.g., a hypotube, extending from a tip 121 at the distal end of the cannula extension 120 toward the proximal end of the cannula extension 120. The hypotube 123 is formed from a material, e.g., a stainless steel rod, having sufficient rigidity to allow the cannula extension 120 to be advanced through a conventional ECMO reperfusion cannula such that a distal region of the expandable conduit 122 may be positioned with its outlet extending beyond the renal arteries of the patient, preferably within the patient's ascending aorta or proximate to the aortic arch. For example, the hypotube 123 may have a lumen sized and shaped to receive a guidewire such that the extension cannula 120 may be advanced over the guidewire through a conventional ECMO reperfusion cannula and through the lumen of the hypotube 123 to the target location. As shown in FIG. 20C, which is a cross-sectional view of the extension cannula 120 along line CC in FIG. 20A, the hypotube 123 may be positioned on a single side of the expandable conduit 122. For example, as shown in FIG. 20C, the hypotube 123 may be positioned along an inner wall of the expandable conduit 122. Thus, the hypotube 123 may extend from the tip 121, along the inner surface of the expandable conduit 122, toward the ECMO cannula. Additionally, the hypotube 123 may extend along the inner surface of the ECMO cannula. Thus, the hypotube 123 is not in the blood flow path through the lumen of the expandable conduit 122. In some embodiments, instead of extending from the tip 121 along the inner surface of the expandable conduit 122, the hypotube 123 may extend from the tip 121 along the outer surface of the expandable conduit 122, and thus along the outer surface of the ECMO cannula, or, alternatively, the hypotube 123 may be embedded within the biocompatible material that forms the expandable conduit 122, e.g., the membrane of the expandable conduit 122, such that the hypotube 123 extends from the tip 121, through the membrane of the expandable conduit 122, toward the ECMO cannula, e.g., along the entire length of the expandable conduit 122.

[0157] Referring again to FIG. 20A, the distal end of the hypotube 123 may include an atraumatic tip 121 that may be coupled to a distal region of the expandable conduit 122. Additionally, as shown in FIG. 20A, the extension cannula 120 may further include a circumferential support 124 positioned at the distal region of the expandable conduit 122 and facilitating expansion of the expandable conduit 122 within the patient's vasculature. The support 124 may be self-expandable between a collapsed delivery state and an expanded deployed state (e.g., upon exposure from a delivery sheath). As shown in FIG. 20A, the support 124 may have a circumferential profile in the expanded deployed state. The support 124 may be embedded within a biocompatible material that forms the expansion conduit 122. Additionally or alternatively, the support 124 may be coupled to an inner surface of the expandable conduit 122, or an outer surface of the expandable conduit 122, or both. Additionally, in some embodiments, the support 124 may also be coupled to the hypotube 123. In one embodiment, the support 124 is not self-expandable such that when blood flows through the lumen of the expandable conduit 124, the support 124 transitions from a collapsed delivery state to an expanded deployed state, thereby causing the expandable conduit 122 to fill with blood. In some embodiments, the cannula extension 120 may not include a support 124.

[0158] The expandable conduit 122 is made from a soft, flexible material such as polyethylene, polyurethane, or nylon and may include a plurality of pores 125 in its distal region that allow blood to perfuse through the material as flow is directed through the lumen of the expandable conduit 122. The pores 125 may be sized and shaped to cause the expandable conduit 122 to fill with blood and transition from a collapsed delivery state to an expanded deployed state as blood flows from the ECMO machine, through a conventional ECMO reperfusion cannula, and through the lumen of the expandable conduit 122, with blood flow exiting the expandable conduit 122 through the pores 125. In some embodiments, the biocompatible polymer coating may include additional pores proximal to the pores 125 that allow blood to perfuse laterally through the material, thereby reducing spraying from the pores 125. Further, the expandable conduit 122 has a sufficient length, e.g., 15-120 cm, or preferably 20-80 cm, or 30-50 cm, to extend from the exit of a conventional ECMO reperfusion cannula to a location above the patient's renal arteries, and more preferably into the thoracic aorta. Notably, the lightweight sock-like construction provides advantages, including ease of deployment, e.g., through a tortuous or diseased aorta, as well as the absence of any impingement on the spinal cord when most patients are lying flat as the use of a stiff cannula may impinge on the spinal cord. Additionally, as described in more detail below with respect to FIG. 23A, the expandable conduit may include one or more longitudinally extending holes disposed along a tapered portion of the expandable conduit extending proximally from the tip and / or one or more holes disposed on the tip.

[0159] 20B, an additional alternative extension cannula is provided. The extension cannula 120' may be constructed similarly to the extension cannula 120, except that the extension cannula 120' may further include a connecting structure 126, e.g., one or more umbrella-like struts, extending between the tip 121' and the support 124', thereby providing reinforcing support to a distal region of the extension cannula 120'. The connecting structure 126 may be self-expandable between a collapsed delivery state and an expanded deployed state (e.g., upon exposure from a delivery sheath). As shown in FIG. 20B, the connecting structure 126 may have a linear shape in the expanded deployed state. The connecting structure 126 may be embedded within a biocompatible material forming the extension conduit 122'. Additionally or alternatively, the connecting structure 126 may be coupled to an inner surface of the expandable conduit 122', or an outer surface of the expandable conduit 122', or both. In one embodiment, the connecting structure 126 is not self-expandable such that when blood flows through the lumen of the expandable conduit 122', the connecting structure 126 transitions from a collapsed delivery state to an expanded deployed state, thereby causing the expandable conduit 122' to fill with blood.

[0160] 21A, an additional alternative cannula extension is provided. As shown in FIG. 21A, the cannula extension 130 may include an expandable conduit 132 and an elongated shaft 133, e.g., a hypotube, extending from an atraumatic tip 131 at the distal end of the cannula extension 130 toward the proximal end of the cannula extension 130. The hypotube 133 is formed from a material, e.g., a stainless steel rod, having sufficient rigidity to allow the cannula extension 130 to be advanced through a conventional ECMO reperfusion cannula such that the distal region of the expandable conduit 132 may be positioned with its outlet extending beyond the renal arteries of the patient, preferably within the patient's ascending aorta or adjacent to the aortic arch. For example, the hypotube 133 may have a lumen sized and shaped to receive a guidewire such that the extension cannula 130 may be advanced through a conventional ECMO reperfusion cannula and over the guidewire via the lumen of the hypotube 133 to the target location. As shown in FIG. 21C, which is a cross-sectional view of the extension cannula 130 along line CC in FIG. 21A, the hypotube 133 may be positioned in a central location within the lumen of the expandable conduit 132. Specifically, as shown in FIG. 21A, the hypotube 133 may be centered within the lumen of the expandable conduit 132 while extending along the longitudinal axis of the extension cannula 130, providing additional stability in terms of cannula movement into the aorta. Thus, the hypotube 133 may extend from the tip 131, through the lumen of the expandable conduit 133, toward the ECMO cannula. Additionally, the hypotube 133 may extend through the lumen of the ECMO cannula. The hypotube 133 does not form part of the blood flow path through the lumen of the expandable conduit 132 .

[0161] The expandable conduit 132 is made from a soft, flexible material such as polyethylene, polyurethane, or nylon and may include a plurality of pores 135 in its distal region that allow blood to perfuse through the material as flow is directed through the lumen of the expandable conduit 132. The pores 135 may be sized and shaped to cause the expandable conduit 132 to fill with blood and transition from a collapsed delivery state to an expanded deployed state as blood flows from the ECMO machine, through a conventional ECMO reperfusion cannula, and through the lumen of the expandable conduit 132, with blood flow exiting the expandable conduit 132 through the pores 135. In some embodiments, the biocompatible polymer coating may include additional pores proximal to the pores 135 that allow blood to perfuse laterally through the material, thereby reducing spraying from the pores 135. Further, the expandable conduit 132 has a sufficient length, e.g., 15-120 cm, or preferably 20-80 cm, or 30-50 cm, to extend from the exit of a conventional ECMO reperfusion cannula to a location above the patient's renal arteries, and more preferably into the thoracic aorta. Notably, the lightweight sock-like construction provides advantages, including, for example, ease of deployment through a tortuous or diseased aorta, as well as the absence of any impingement on the spinal cord when most patients are lying flat as the use of a stiff cannula may impinge on the spinal cord. Additionally, as described in more detail below with respect to FIG. 23B, the expandable conduit may include one or more longitudinally extending holes disposed along a tapered portion of the expandable conduit extending proximally from the tip and / or one or more holes disposed on the tip.

[0162] 21B, an additional alternative cannula extension is provided. The cannula extension 130' may be constructed similarly to the cannula extension 130, except that the cannula extension 130' may further include a circumferential support 134 and a connecting structure 136, e.g., one or more umbrella-like struts, extending between the tip 131' and the support 134, thereby providing reinforcing support to a distal region of the cannula extension 130'. As shown in FIG. 21B, the support 134 may be positioned at a distal region of the expandable conduit 132' to facilitate expansion of the expandable conduit 132' within the patient's vasculature. The support 134 may be self-expandable between a collapsed delivery state and an expanded deployed state (e.g., upon exposure from a delivery sheath). As shown in FIG. 21B, the support 134 may have a circumferential profile in the expanded deployed state. The supports 134 may be embedded within the biocompatible material that forms the expansion conduit 132'. Additionally or alternatively, the supports 134 may be coupled to an inner surface of the expandable conduit 132', or an outer surface of the expandable conduit 132', or both. In one embodiment, the supports 134 are not self-expandable such that as blood flows through the lumen of the expandable conduit 134, the supports 134 transition from a collapsed delivery state to an expanded deployed state, thereby causing the expandable conduit 132' to fill with blood. In some embodiments, the extension cannula 130 of FIG. 21A may also include circumferential supports.

[0163] The connecting structures 136 may be self-expandable between the collapsed delivery state and the expanded deployed state (e.g., upon exposure from a delivery sheath). As shown in FIG. 21B, the connecting structures 136 may have a linear shape in the expanded deployed state. Alternatively, the connecting structures 136 may have a curved shape in the expanded deployed state. The connecting structures 136 may be embedded within a biocompatible material forming the expansion conduit 132'. Additionally or alternatively, the connecting structures 136 may be coupled to an inner surface of the expandable conduit 132', or an outer surface of the expandable conduit 132', or both. In one embodiment, the connecting structures 136 are not self-expandable such that when blood flows through the lumen of the expandable conduit 132', the connecting structures 136 transition from the collapsed delivery state to the expanded deployed state, thereby causing the expandable conduit 132' to fill with blood.

[0164] 22A-22C, the extension cannula described herein may include pores of various arrangements and configurations disposed on at least the distal region of the expandable conduit, the pores being sized and shaped to allow blood to flow therethrough, thereby avoiding stagnation or blood clogging along the length of the cannula, and distributing the flow more evenly within the aorta, thereby also avoiding left ventricular loading. As shown in FIG. 22A, the plurality of pores may include a first plurality of pores 74a and a second plurality of pores 74b, which may have a longitudinally extending shape, e.g., an oval shape. Additionally, the pores 74a and pores 74b may be disposed laterally along the length of at least the distal region of the expandable conduit, e.g., expandable conduit 72, such that the pores 74b are proximal to the pores 74a. In addition, pores 74a may be spaced apart from one another along the expandable conduit by a distance that is less than the distance that pores 74b are spaced apart along the expandable conduit.

[0165] As shown in FIG. 22B, the multiple pores can include pores 74c that can have a longitudinally extending shape, e.g., an oval shape, and can be equally spaced apart from one another along at least the length of the expandable conduit, e.g., the distal region of the expandable conduit 72.

[0166] As shown in FIG. 22C, the plurality of pores may include a first plurality of pores 74d and a second plurality of pores 74e. The pores 74d may have a circular shape and may be arranged circumferentially around at least the distal region of the expandable conduit, e.g., the expandable conduit 72. As shown in FIG. 22C, the plurality of pores 74d may include a plurality of rows of circumferentially arranged pores. Although FIG. 22C illustrates four rows of circumferentially arranged pores 74d, as would be understood by one of ordinary skill in the art, the pores 74d may include fewer than or more than four rows of circumferentially arranged pores. Additionally, the pores 74e may include a plurality of pores arranged laterally along the length of at least the distal region of the expandable conduit. As shown in FIG. 22C, the pores 74e may be proximal to the pores 74d. As would be understood by one of 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, the circumferentially disposed pores may have a longitudinally extending shape, or any combination thereof.

[0167] 23A, an alternative cannula extension having one or more bleed holes is provided. The cannula extension 120'' may be constructed similarly to the cannula extensions 120, 120'. For example, the cannula extension 120'' may include an expandable conduit 122'' coupled to and extending proximally from the tip 121'' and a hypotube 123'' coupled to and extending proximally from the tip 121'' along a side of the expandable conduit 122''. As described above, the hypotube 123'' may extend along an inner surface of the expandable conduit 122'', may extend along an outer surface of the expandable conduit 122'', or the hypotube 123'' may be embedded within the membrane of the expandable conduit 122'', for example, extending within the expandable conduit 122'' along the entire length of the expandable conduit 122''. Additionally, as described above, the expandable conduit 122'' may include a plurality of pores (not shown) disposed on at least a distal region of the expandable conduit 122'', the pores being sized and shaped to allow blood to flow through the pores, thereby avoiding stagnation or clogging of blood along the length of the cannula, and also to distribute flow more evenly within the aorta, thereby avoiding left ventricular loading. The pores may be disposed, if applicable, on a distal region of the expandable conduit 122'' proximal to the support portion 124'' and / or on a distal tapered portion of the support portion 124'', for example, between adjacent outflow holes 127.

[0168] The cannula extension 120″ differs from the cannula extension 120, 120′ in that the cannula extension 120″ may further include one or more effluent holes 127 disposed on at least a tapered portion of the expandable conduit 122″, e.g., a portion of the expandable conduit 122″, the cross-sectional area of ​​which decreases distally toward the tip 121″ and is sized and shaped to allow blood to flow through the effluent holes 127, e.g., from within the lumen of the expandable conduit 122″ and into the vascular system of the patient. As shown in FIG. 23A, the effluent holes 127 may be disposed circumferentially around the tapered portion of the expandable conduit 122″ and extend longitudinally along the tapered portion having a slit-like geometry. As would be understood by one skilled in the art, although FIG. 23A shows the effluent holes 127 having a triangular shape, the effluent holes 127 may have other longitudinally extending shapes, e.g., oval, rectangular, trapezoidal, etc. Preferably, the width of outflow holes 127 increases proximally from tip 121'' to improve flow therethrough.

[0169] In addition, the cannula extension 120'' may include one or more holes 128 extending through the tip 121'', the one or more holes 128 being sized and shaped to allow blood to flow therethrough, e.g., from within the lumen of the expandable conduit 122'', and into the patient's vascular system. For example, the holes 128 may be formed by drilling holes through the tip 121''. By allowing blood flow through the holes 128, flow may be maintained and stasis may be removed from the area, thereby preventing and / or reducing blood clot formation, e.g., within the distal end of the expandable conduit 122'', between the distal end of the outflow hole 127 and the interior surface of the tip 111''. As will be appreciated by one of ordinary skill in the art, outflow holes and / or tip holes may be incorporated into other cannula extensions described herein, e.g., the cannula extensions 70, 70', 70'', 70'''.

[0170] 23B, another alternative cannula extension having one or more outflow holes is provided. The cannula extension 130'' may be constructed similarly to the cannula extensions 130, 130'. For example, the cannula extension 130'' may include an expandable conduit 132'' coupled to and extending proximally from the tip 131'' and a hypotube 133'' coupled to and extending proximally from the tip 131'' along a central longitudinal axis of the expandable conduit 122''. In addition, as described above, the expandable conduit 132'' may include multiple pores (not shown) disposed on at least a distal region of the expandable conduit 132'', the pores being sized and shaped to allow blood to flow through the multiple pores, thereby avoiding stagnation or clogging of blood along the length of the cannula, and also to distribute the flow more evenly within the aorta, thereby avoiding loading of the left ventricle. The pores may be located on a distal region of the expandable conduit 132 ″ proximal to the outflow holes 137 and / or on tapered portions between adjacent outflow holes 137 , for example.

[0171] The cannula extension 130'' differs from the cannula extension 130, 130' in that the cannula extension 130'' may further include one or more outflow holes 137 disposed on at least a tapered portion of the expandable conduit 132'', e.g., a portion of the expandable conduit 132'', the outflow holes 137 having a cross-sectional area that decreases distally toward the tip 131'', and that are sized and shaped to allow blood to flow through the outflow holes 137, e.g., from within the lumen of the expandable conduit 132'', and into the patient's vascular system. As shown in FIG. 23B, the outflow holes 137 may be disposed circumferentially around the tapered portion of the expandable conduit 132'', and extend longitudinally along the tapered portion having a slit-like geometry. As would be understood by one of ordinary skill in the art, although FIG. 23B shows the outflow holes 137 having a trapezoidal / rectangular shape, the outflow holes 137 may have other longitudinally extending shapes, e.g., oval, rectangular, triangular, etc. Preferably, the width of the outflow holes 137 increases proximally from the tip 131″ to improve flow therethrough. Additionally, the extension cannula 130″ may include one or more holes 138 extending through the tip 131″ and sized and shaped to allow blood to flow through the one or more holes 138, e.g., from within the lumen of the expandable conduit 132″ and into the patient's vasculature. For example, the holes 138 may be formed by drilling holes through the tip 131″. By allowing blood flow through holes 138, flow may be maintained and stasis may be removed from the area, thereby preventing and / or reducing blood clot formation, for example, within the distal end of expandable conduit 132'', between the distal end of outflow hole 137 and the inner surface of tip 131''.

[0172] FIG. 24 is a graph illustrating stroke risk for patients undergoing various therapies, including VA-ECMO. As shown, patients undergoing VA-ECMO generally have the highest risk of total stroke, e.g., acute ischemic stroke and hemorrhagic stroke. In accordance with the principles of the present invention, the systems and methods described herein are expected to provide oxygenated blood to the cerebral vasculature and provide antegrade flow from the outlet of a self-expanding conduit. This, in turn, is expected to reduce the risk of ischemic stroke and reduce blood flow and pressure that may induce kidney damage.

[0173] Further anticipated benefits of the system and method of the present invention are described with reference to FIG. 25. FIG. 25 illustrates a situation referred to as "North-South syndrome" that may occur in patients on ECMO, particularly those with impaired pulmonary function. In such cases, the heart is beating, but the blood returned to the circulation by the left ventricle may be poorly oxygenated. In this case, if a conventional ECMO return catheter is employed, the oxygenated blood reperfused into the patient mixes with the antegrade flow deoxygenated blood from the lungs, resulting in differential hypoxia. Because the extension cannula of the present invention is designed to deliver blood into the ascending aorta, the system and method of the present invention is expected to significantly improve the effect of impaired pulmonary function and reduce the incidence and severity of North-South syndrome.

[0174] Preclinical data from experiments utilizing an extension cannula constructed according to the principles of the present invention demonstrates superior performance compared to conventional ECMO return cannulas. FIG. 26 is a series of graphs comparing various parameters measured during standard VA-ECMO cannulation with those measured using an extension cannula of the present invention (defined in FIG. 26 as "alternative cannulation"). In particular, the alternative cannulation of the present invention results in reduced pulmonary mean arterial pressure (MAP), reduced right arterial pressure, reduced pulmonary capillary wedge pressure, reduced renal artery flow velocity, and reduced renal interstitial pressure (organ pressure) compared to standard VA-ECMO cannulation. These findings suggest that placement of an extension cannula may reduce cardiac, pulmonary, and renal injury compared to standard VA-ECMO alone. Specifically, this data shows reduced cardiac pressures (right atrial pressure and pulmonary capillary wedge pressure), normal renal artery velocity, and normal renal interstitial (organ) pressure with alternative cannulation as opposed to standard cannulation (delivery of blood to the femoral artery). Additionally, as shown in FIG. 27, the alternative cannulation of the present invention provides increased pulsatile arterial flow in the renal and femoral arteries as compared to standard VA-ECMO cannulation. Compared to sham-operated animals, standard femoral cannulation ECMO reduces renal and femoral artery pulse pressures, e.g., pulsatility. Compared to standard cannulation, alternative cannulation (delivery of blood to the thoracic aorta) has increased renal and femoral artery pulse pressures, e.g., pulsatility. Improved physiological pulsatility is further associated with less injury.

[0175] 28 and 29 provide further comparison of the use of the alternative cannulation of the present invention compared to standard ECMO cannulation, demonstrating improved renal artery pulsatility and reduced microvascular resistance in the kidney. With respect to FIG. 28, compared to standard cannulation, the alternative (irrigation) cannulation preserves pulsatility in the renal artery after 3 hours of pumping. With respect to FIG. 29, compared to standard cannulation, the alternative (irrigation) cannulation preserves pulsatility (renal resistance index) and reduces renal artery microvascular resistance in the renal artery after 2 and 6 hours of pumping. Similarly, FIG. 30 demonstrates that the alternative cannulation of the present invention ("ALT ECMO") results in lower levels of kidney injury molecule 1 (KIM-1) in the urine, indicating less kidney injury is suffered by the patient. Compared to standard VA-ECMO, ALT ECMO is associated with lower (normal) levels of kidney injury markers in the urine.

[0176] Figures 31A and 31B provide further comparison of the use of the alternative cannulation of the present invention compared to standard ECMO cannulation, demonstrating a significant and unexpected reduction in both left and right ventricular work. Figure 31A is a graph of measured pressure versus volume, including traces for the left and right ventricles, 60 minutes after infarction, immediately after the start of arterial ECMO cannulation into the femoral artery at a standard infrarenal outlet location, and 10 minutes after standard arterial ECMO cannulation. The area within each pressure versus volume loop, referred to as "PVA", is a measure of the work performed by the heart during the cardiac cycle. The graph in Figure 31A shows that the pressure / volume loop for the left ventricle (LV) is substantially unchanged by ECMO reperfusion. Similarly, the right ventricle (RV) does not experience a significant reduction in work after standard arterial ECMO cannulation. As a possible explanation, and not intended to be limiting, it is hypothesized that left and right ventricular work remains essentially unchanged because the introduction of continuous high flow down the renal arteries causes the blood column to stagnate in the descending aorta, which in turn causes LV pressure to remain high. Thus, it is believed that the heart must continue to work to overcome the resistance to antegrade flow created by the ECMO infused blood. Thus, during standard ECMO cannulation, femoral delivery of arterial blood pressurizes the entire aorta, thereby increasing the load against which the native heart must pump.

[0177] In contrast, as shown in Figure 31B, when the extension cannula of the present invention is deployed to expand the ECMO outlet in the aortic arch, both the left ventricle (LV) and right ventricle (RV) experience a significant reduction in work after the onset of ECMO activation and thereafter, as compared to standard arterial ECMO cannulation in Figure 31A. Specifically, the pressure / volume loop for the left ventricle (LV) is significantly reduced, and the pressure / volume loop for the right ventricle (RV) is further reduced, thus illustrating the effectiveness of the extension cannula of the present invention in reducing cardiac work during ECMO reperfusion. Again, by way of explanation and not intended to be limiting, it is hypothesized that the significant reduction in left and right ventricular work is due to the delivery of blood into the aortic arch, which increases antegrade blood flow to the descending aorta and arteries adjacent to the aortic arch. Thus, the resulting forward flow is fully developed during the first 10 minutes of ECMO reperfusion, unloading the LV, thereby causing a smaller cardiac output, but at a much lower pressure. Furthermore, it is believed that the reduced load on the LV may assist blood to shift to the lungs, further reducing RV work. Thus, by delivering blood into the aortic arch, the arterial tree is not pressurized, thereby avoiding the increased pressure load against which the heart would otherwise have to work, which allows for more effective venous drainage of the heart, and therefore reduced RV and LV volumes, without the expense of increasing ventricular pressures.

[0178] Figure 32 is a graph illustrating the pressure volume area (PVA), stroke work (SW), and end diastolic pressure (EDP) associated with the use of standard conventional VA-ECMO cannulation and the alternative extended cannulation of the present invention. As shown in Figure 32, despite equal flow rates through the VA-ECMO circuit (bottom right) compared to standard conventional VA-ECMO, the use of the alternative extended cannulation of the present invention reduces PVA, SW, and EDP, thereby demonstrating that the alternative extended cannulation of the present invention reduces cardiac workflow.

[0179] Figure 33A illustrates the infarct size associated with the use of standard conventional ECMO cannulation and the alternative cannulation of the present invention. As shown in Figure 33B, the infarct size associated with the use of the alternative extended cannulation of the present invention is much smaller than the infarct size associated with standard ischemia reperfusion injury (IRI) and the use of standard conventional ECMO cannulation.

[0180] FIG. 34 is a graph illustrating the oxygen consumption rate (OCR) indicative of mitochondrial function associated with standard ischemia-reperfusion injury (IRI) and standard conventional ECMO cannulation with and without the Impella device and the use of the alternative extended cannulation of the present invention. Mitochondria are known as the "power plants" of the cell that generate ATP through oxidative phosphorylation (OXPHOS) complexes present within the inner mitochondrial membrane. These complexes convert NADH, i.e., ubiquinone oxidoreductase (complex I), succinate dehydrogenase (complex II), ubiquinol-cytochrome c oxidoreductase (complex III, or cytochrome bc 1 These enzymes are known as cytochrome c oxidase (complex IV), cytochrome c oxidase (complex IV), and ATP synthase (complex V).

[0181] Complex I (CI) is the largest and most complexed component of the respiratory chain. Using bovine heart as a model system, previous studies have characterized all complex I subunits and cloned the encoding genes. Mitochondrial CI constitutes 40% of the proton-motive force required to maintain ATP synthase in the electron transport chain (ETC). Recent studies have shown that unloading the left heart using a mechanical pump can reduce myocardial damage and preserve mitochondrial CI function. See, for example, Lija Swain, PhD, et al., Transvalvular Ventricular Unloading before Reperfusion in Acute Myocardial Infarction, Journal of the American College of Cardiology, Vol. 76, No. 6 (2020). Studies have further found that the use of VA-ECMO during a heart attack fails to reduce left heart load, 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 is initiated. The study demonstrated that using the alternative extended cannulation of the present invention with VA-ECMO reduces left heart load, reduces myocardial injury, and improves mitochondrial CI function.

[0182] For example, as shown in FIG. 34, the use of the alternative extended cannulation of the present invention with VA-ECMO preserves mitochondrial CI function as measured by oxygen consumption rate (OCR), which when compromised, impacts myocardial injury and infarct size, compared to IRI alone, standard conventional VA-ECMO alone, and standard conventional VA-ECMO with Impella device. Furthermore, as shown in FIG. 35, when comparing non-infarct zones, mitochondrial CI function is significantly reduced in the infarct zone after IRI alone, standard conventional VA-ECMO alone, and standard conventional VA-ECMO with Impella device. In contrast, mitochondrial CI function is significantly higher in the infarct zone after treatment using the alternative extended cannulation of the present invention with VA-ECMO. These data identify for the first time that a delivery point for arterial blood returning from VA-ECMO facilitates a cardioprotective effect on the heart, which has implications for any patient undergoing VA-ECMO, particularly those undergoing VA-ECMO who have suffered a heart attack or heart injury.

[0183] Although various illustrative embodiments of the present invention are described above, it will be apparent to those skilled in the art that various changes and modifications may be made therein without departing from the present invention. For example, as will be understood by those skilled in the art, the systems and methods described herein are not limited for use with VA-ECMO systems. For example, the extension cannula of the present invention may also be used with, for example, veno-venous ECMO (VV-ECMO) systems. Furthermore, the extension cannula and in-line connector described herein may be used with a conventional ECMO drainage catheter, such that the extension cannula extends from a drainage catheter in the femoral vein to the pulmonary artery or right ventricle of the patient, thereby allowing blood to be pumped directly out of the heart and effectively function as a ventricular assist device. The appended claims are intended to cover all such changes and modifications that fall within the true scope of the present invention.

[0184] As shown in Figures 36A and 36B, any of the extension cannulas described herein, e.g., extension cannulas 10, 10', 10", 10", 70, 70', 70", 110, 100', 120, 120', which may be used with a conventional ECMO drainage catheter 200, may be used in conjunction with a conventional ECMO drainage catheter 200 in fluid communication with an ECMO drainage machine 201 such that a pore of the expandable conduit, e.g., pore 74 of expandable conduit 72, is disposed within the pulmonary artery PA. For example, as shown in Figure 36A, the extension cannula may be inserted via a femoral vein approach and have a length such that the expandable conduit 72 extends through the femoral vein, inferior vena cava IVC, right atrium RA, and right ventricle RV such that pore 74 is disposed within the pulmonary artery PA. Thus, the extension cannula may provide right heart support by draining blood from or delivering blood to the pulmonary artery PA through the expandable conduit 72 and via the pores 74. In some embodiments, the extension cannula may have a length such that the pores 74 are positioned within the right ventricle RV, thereby draining blood from or delivering blood to the right ventricle RV. Alternatively, the extension cannula may have a length such that the distal end of the extension cannula is positioned within the pulmonary artery PA, and the pores 74 are positioned in a distal region of the extension cannula such that the pores 74 are positioned within both the pulmonary artery PA and the right ventricle RV, thereby draining blood from or delivering blood to both the pulmonary artery PA and the right ventricle RV.

[0185] 36B, the extension cannula may be inserted via an internal jugular vein approach with the expandable conduit 72 extending through the internal jugular vein, the superior vena cava SVC, the right atrium RA, and the right ventricle RV with the aperture 74 disposed within the pulmonary artery PA. Thus, the extension cannula may provide right heart support by draining blood from or delivering blood to the pulmonary artery PA through the expandable conduit 72 and via the aperture 74. In some embodiments, the extension cannula may have a length such that the aperture 74 is disposed within the right ventricle RV, thereby draining blood from or delivering blood to the right ventricle RV. Alternatively, the extension cannula may have a length such that the distal end of the extension cannula is disposed within the pulmonary artery PA and the pores 74 are disposed in a distal region of the extension cannula such that the pores 74 are disposed within both the pulmonary artery PA and the right ventricle RV, thereby draining blood from or delivering blood to both the pulmonary artery PA and the right ventricle RV. As will be appreciated by those skilled in the art, the extension cannula described above for use with a conventional ECMO cannula to deliver oxygenated blood directly to a location above the renal veins of a patient may also have a length such that the distal end region of the extension cannula, and thus the pores of the expandable conduit, are disposed within the pulmonary artery and / or right ventricle, respectively, such that oxygenated blood may be delivered directly to the pulmonary artery and / or right ventricle.

[0186] The appended claims are intended to cover all such changes and modifications that fall within the true scope of this invention.

Claims

1. An extension cannula for use with an ECMO return cannula having a lumen configured to define an inlet, outlet, and blood flow pathway, wherein the extension cannula is An elongated shaft having a proximal end and a distal region, A flexible conduit coupled to the distal region of the elongated shaft, having a proximal end, a distal end, and an internal lumen, wherein the proximal end is configured to engage with the outlet of the ECMO return cannula and to form a continuity of the blood flow pathway through the lumen of the ECMO return cannula, and the flexible conduit is configured to transition between a folded inserted state and an expanded, unfolded state when communicating with blood flow from the ECMO machine through the internal lumen, A connecting structure configured to connect the flexible conduit to the distal region of the elongated shaft, Equipped with, The elongated shaft is configured to advance the flexible conduit and position its distal end beyond the patient's renal blood vessels. The flexible conduit is an extension cannula having a selected length such that when the extension cannula is in the expanded and unfolded state, its proximal end is located within the outlet of the ECMO return cannula at a location proximal to the patient's renal blood vessels, and its distal end extends beyond the outlet of the ECMO return cannula and the patient's renal blood vessels.

2. The extension cannula according to claim 1, wherein the elongated shaft comprises a hypotube having a lumen, and the lumen is configured to receive a guidewire through it.

3. The extension cannula according to claim 1, wherein the flexible conduit comprises at least one of polyethylene or nylon.

4. The extension cannula according to claim 1, wherein the flexible conduit is made of a biocompatible fabric.

5. The extension cannula according to claim 1, wherein the outlet of the flexible conduit is provided with one or more pores located in the distal region of the flexible conduit.

6. The extension cannula according to claim 1, wherein the distal portion of the flexible conduit has a tapered portion having a cross-sectional area that decreases toward the distal end of the flexible conduit, and the outlet of the flexible conduit has one or more outflow holes located at least on the tapered portion of the flexible conduit.

7. The extension cannula according to claim 6, wherein the one or more outflow holes are arranged circumferentially around the tapered portion of the flexible conduit and extend longitudinally along the tapered portion.

8. The extension cannula according to claim 6, wherein the width of one or more outflow holes increases in the proximal direction.

9. The extension cannula according to claim 1, wherein the distal end of the elongated shaft is provided with a tip connected to the distal end of the flexible conduit via the connecting structure.

10. The extension cannula according to claim 9, wherein the connection structure comprises one or more umbrella-shaped support columns.

11. The extension cannula according to claim 9, wherein the elongated shaft has a selected length such that the elongated shaft extends proximal from the tip through the internal lumen of the flexible conduit and beyond the proximal end of the flexible conduit.

12. The extension cannula according to claim 9, wherein the tip comprises one or more holes extending through it, the one or more holes being sized and shaped to allow blood flow through them and to reduce the formation of blood clots adjacent to the tip within the flexible conduit.

13. The extension cannula according to claim 1, wherein the elongated shaft is configured such that the blood flow pathway does not pass through the elongated shaft.

14. The extension cannula according to claim 1, wherein the elongated shaft extends proximal from the distal end of the flexible conduit along the side surface of the flexible conduit.

15. The extension cannula according to claim 1, wherein the elongated shaft extends proximal within the lumen from the distal end of the flexible conduit along the longitudinal axis of the flexible conduit.

16. The extension cannula according to claim 1, wherein at least a portion of the elongated shaft is embedded in the membrane of the flexible conduit such that at least a portion of the elongated shaft extends proximal within the flexible conduit from the distal end of the flexible conduit.

17. The extension cannula according to claim 1, wherein the proximal end of the flexible conduit is configured to engage with the outlet of the ECMO return cannula by a fixed stent.

18. The extension cannula according to claim 17, wherein the fixing stent is self-expandable.

19. The extension cannula according to claim 1, wherein the proximal region of the flexible conduit is configured to be fixedly connected to the ECMO return cannula within the outlet of the ECMO return cannula.

20. The extension cannula according to claim 19, wherein the proximal region of the flexible conduit is configured to be fixed and bonded to the ECMO return cannula via at least one of a heat seal, a two-component polyurethane adhesive, or a segmented polyurethane bond.

21. The extension cannula according to claim 1, wherein the flexible conduit is inserted through the lumen of the ECMO return cannula in the folded insertion state using the elongated shaft and is configured to transition to the expanded unfolded state when in communication with the blood flow from the ECMO machine.

22. The extension cannula according to claim 1, wherein the elongated shaft is configured to advance the flexible conduit and position the proximal end of the flexible conduit within the outlet of the ECMO return cannula.

23. The extension cannula according to claim 1, further comprising a sheath configured to cover and be removable over the flexible conduit in order to hold the flexible conduit in the folded inserted state.

24. An extension cannula system, wherein the extension cannula system is The extension cannula according to claim 1, An in-line connector configured to be connected to the ECMO return cannula, Equipped with, The aforementioned inline connector is An inlet configured to be removablely coupled to the outlet of the ECMO circuit, An outlet is configured to communicate with the inlet and to be removably connected to the ECMO return cannula, The side arm has a lumen that is in fluid communication with the lumen of the elongated shaft. It has, An extension cannula system in which the lumen and elongated shaft of the side arm are sized and shaped to receive a guidewire through them.

25. The extension cannula system according to claim 24, further comprising a stylet, the stylet being inserted through the lumen of the side arm of the inline connector and through at least a portion of the lumen of the elongated shaft, and configured to prevent blood flow through the lumen of the elongated shaft during operation of the ECMO machine.

26. The extension cannula system according to claim 24, further comprising a cap, the cap being configured to be removably engaged with the side arm of the inline connector and to prevent blood flow through the lumen of the elongated shaft during operation of the ECMO machine.

27. A kit for use with an ECMO machine, the kit comprises, A cannula comprising a proximal region having an inlet configured to be coupled to the ECMO machine, and an outlet configured to be positioned at a location within the patient's vascular system proximal to the patient's renal blood vessels, Extension cannula and Equipped with, The aforementioned extension cannula is, A conduit comprising a flexible, collapsible tube, wherein the conduit has a proximal end, a distal end, a length extending between them, and a lumen in an expanded, unfolded state, and the conduit is configured to transition from a folded, inserted state to the expanded, unfolded state when in communication with blood flow from the ECMO machine, An elongated shaft having a distal region connected to the distal end of the conduit and Equipped with, The elongated shaft is configured to advance the conduit in the folded insertion state and to position its distal end beyond the patient's renal blood vessels. The length of the conduit is selected such that the distal end extends beyond the patient's renal blood vessel when the proximal end is located within the outlet at the location in the patient's vascular system proximal to the patient's renal blood vessel, and the conduit transitions to the expanded and deployed state in the presence of blood flow from the ECMO machine such that the lumen forms a continuity of blood flow pathway through the cannula.

28. The kit according to claim 27, wherein the elongated shaft comprises a hypotube having a lumen, and the lumen is configured to receive a guidewire through it.

29. The kit according to claim 27, wherein the flexible conduit comprises a distal region and includes a number of pores configured to allow the blood flow to exit the lumen, the number of pores comprising at least one of one or more laterally arranged pores or one or more circumferentially arranged pores.

30. The kit according to claim 27, wherein the proximal end of the conduit is integrally formed with the outlet of the cannula.

31. The kit according to claim 30, wherein the integrally formed cannula and conduit have a length of 80 to 100 cm.

32. The kit according to claim 30, wherein the conduit has a length of 40 to 70 cm.

33. The kit according to claim 27, wherein the proximal end of the conduit is attached to the outlet by a stent.

34. The system further comprises an in-line connector configured to be coupled to the ECMO machine and the cannula, The aforementioned inline connector is An inlet configured to be removablely coupled to the outlet of the ECMO circuit, An outlet is configured to communicate with the inlet and to be removably coupled to the inlet of the cannula, The side arm has a lumen that is in fluid communication with the lumen of the elongated shaft. It has, The kit according to claim 27, wherein the lumen and elongated shaft of the side arm are sized and shaped to receive a guide wire through them.

35. A flexible extension cannula for improving systemic perfusion, for use with an ECMO return cannula in fluid communication with an ECMO machine, wherein the flexible extension cannula is: The distal end and A long, slender shaft connected to the distal end, Distal region and A proximal region configured to be connected to the outlet of the ECMO return cannula, Multiple pores arranged in the distal region and Equipped with, The distal end of the flexible extension cannula is configured to be advanced within the patient's vascular system via the elongated shaft so that the flexible extension cannula extends from a location proximal to the patient's renal blood vessels to a location beyond the patient's renal blood vessels. The flexible extension cannula is configured to transition from a folded inserted state to an expanded, unfolded state that communicates with the blood flow from the ECMO machine, and the flexible extension cannula has a lumen in the expanded state. A flexible extension cannula, through the lumen of the flexible extension cannula and through the plurality of pores, delivers the blood flow to the location beyond the patient's renal blood vessels, thereby improving systemic perfusion.

36. The flexible extension cannula according to claim 35, further comprising an inline connector, wherein the ECMO return cannula is connected to the ECMO machine via the inline connector, and the inline connector comprises an inlet configured to be removably connected to an outlet of an ECMO circuit, an outlet configured to be in fluid communication with the inlet and to be removably connected to the inlet of the cannula, and a side arm having a lumen in fluid communication with the lumen of the elongated shaft.

37. The system further comprises a guidewire configured to be advanced within the patient's vascular system from a location proximal to the patient's renal blood vessels to a location beyond the patient's renal blood vessels, The flexible extension cannula according to claim 36, wherein the distal end of the flexible extension cannula is configured to advance on the guidewire through the lumen of the elongated shaft until the proximal end of the guidewire extends out of the lumen of the side arm of the inline connector.

38. The flexible extension cannula according to claim 37, wherein the guidewire is configured to be removed from the patient's vascular system through the lumen of the side arm of the inline connector.

39. The flexible extension cannula according to claim 38, further comprising a stylet, the stylet being inserted through the lumen of the side arm of the inline connector and through at least a portion of the lumen of the elongated shaft, and configured to prevent blood flow through the lumen of the elongated shaft during operation of the ECMO machine.

40. The flexible extension cannula according to claim 35, wherein delivering the blood flow through the lumen of the flexible extension cannula and through the plurality of pores to the location beyond the patient's renal blood vessels reduces left ventricular load, reduces myocardial damage, and improves mitochondrial CI function.

41. The flexible extension cannula according to claim 35, wherein the blood flow is delivered through the lumen of the flexible extension cannula, via the plurality of pores, to the location beyond the patient's renal blood vessels, thereby enhancing the effect on impaired lung function and reducing the incidence and severity of North-South syndrome.

42. The flexible extension cannula according to claim 35, wherein delivering the blood flow through the lumen of the flexible extension cannula and through the plurality of pores to the location beyond the patient's renal blood vessels reduces the size of myocardial infarction caused by coronary blood flow occlusion and limits the development of post-infarction heart failure.

43. The flexible extension cannula according to claim 35, wherein the blood flow is delivered through the lumen of the flexible extension cannula, through the plurality of pores, to the location beyond the patient's renal blood vessels, thereby increasing antegrade blood flow to the patient's descending aorta and adjacent arteries, thereby reducing the load on the patient's left ventricle, decreasing cardiac output at lower pressures, and reducing left and right ventricular loads.

44. A kit for use with an ECMO machine, the kit comprises, A cannula comprising a proximal region having an inlet configured to be coupled to the ECMO machine, and an outlet configured to be positioned at a location within the patient's vascular system proximal to the patient's renal blood vessels, An extension cannula, wherein the extension cannula is A flexible conduit having a proximal end, a distal end, a length extending between them, and a lumen in an expanded and unfolded state, wherein the flexible conduit is configured to transition from a folded inserted state to an expanded and unfolded state in which it is in communication with blood flow from the ECMO machine, such that the lumen forms a continuity of blood flow pathway through the cannula. An elongated shaft having a distal region connected to the distal end of the flexible conduit, wherein the elongated shaft is configured to advance the flexible conduit in the folded inserted state and position the distal end beyond the patient's renal blood vessels. It is equipped with an extension cannula, A removable inlet positioned on at least a portion of the flexible conduit and Equipped with, The detachable introduction device is configured to be retracted proximal to the flexible conduit and to be detached from the flexible conduit. The length of the flexible conduit is selected such that the distal end extends beyond the patient's renal vascular system when the proximal end is located within the outlet at the location in the patient's blood vessels proximal to the patient's renal vascular system.

45. The kit according to claim 44, wherein the detachable inlet has a diameter equal to the diameter of the cannula at most.

46. The kit according to claim 44, wherein the detachable inlet is configured to extend along the entire length of the flexible conduit.

47. The kit according to claim 44, wherein the elongated shaft extends proximal from the distal end of the flexible conduit along the side surface of the flexible conduit.

48. The kit according to claim 44, wherein the elongated shaft extends proximal within the lumen along the longitudinal axis of the flexible conduit from the distal end of the flexible conduit.

49. The kit according to claim 48, wherein the elongated shaft extends along the central portion of the lumen.

50. The kit according to claim 44, wherein at least a portion of the elongated shaft is embedded in the membrane of the flexible conduit such that at least a portion of the elongated shaft extends proximal within the flexible conduit from the distal end of the flexible conduit.

51. The kit according to claim 44, wherein the elongated shaft is configured such that the blood flow pathway does not pass through the elongated shaft.

52. The kit according to claim 44, wherein the elongated shaft comprises a hypo tube having a lumen, and the lumen is configured to receive a guidewire through it.

53. The kit according to claim 44, wherein the extension cannula further comprises a support portion coupled to the distal region of the flexible conduit, the support portion extending circumferentially along the flexible conduit and configured to transition from a folded delivery state to an expanded, unfolded state.

54. The kit according to claim 53, wherein the extension cannula further comprises a plurality of connecting structures extending between the distal end of the flexible conduit and the support portion, the plurality of connecting structures being configured to transition from a folded delivery state to an extended, unfolded state.

55. The kit according to claim 54, wherein the distal end of the elongated shaft is provided with a non-traumatic tip configured to be connected to the support via the plurality of connecting structures.

56. The kit according to claim 55, wherein the non-traumatic tip comprises one or more holes extending through it, the one or more holes being sized and shaped to allow blood flow through them to reduce the formation of blood clots adjacent to the tip within the flexible conduit.

57. The kit according to claim 44, wherein the flexible conduit comprises at least one of polyethylene, polyurethane, or nylon.

58. The kit according to claim 44, wherein the outlet of the flexible conduit is provided with one or more pores located in the distal region of the flexible conduit.

59. The kit according to claim 44, wherein the distal portion of the flexible conduit comprises a tapered portion having a cross-sectional area that decreases toward the distal end of the flexible conduit, and the outlet of the flexible conduit comprises one or more outflow holes located at least on the tapered portion of the flexible conduit.

60. The kit according to claim 59, wherein the one or more outflow holes are arranged circumferentially around the tapered portion of the flexible conduit and extend longitudinally along the tapered portion.

61. The kit according to claim 59, wherein the width of the one or more outflow holes increases in the proximal direction.

62. The kit according to claim 44, wherein the proximal end of the flexible conduit is configured to be fixedly connected to the cannula within the outlet of the cannula.

63. The kit according to claim 62, wherein the proximal end of the flexible conduit is configured to be fixed and bonded to the cannula via at least one of a heat seal, a two-part polyurethane adhesive, or a segmented polyurethane bond.

64. The kit according to claim 44, wherein the proximal end of the flexible conduit is integrally formed with the outlet of the cannula.

65. The kit according to claim 64, wherein the integrally formed cannula and flexible conduit have a length of 80 to 100 cm.

66. The kit according to claim 64, wherein the flexible conduit has a length of 40 to 70 cm.

67. The kit according to claim 44, further comprising one or more sensors positioned in the distal region of the extension cannula, wherein the one or more sensors are configured to measure at least one of pressure, flow rate, or oxygen saturation within the patient's vascular system.

68. The system further comprises a console operably coupled to one or more of the sensors, the console being configured to display the measurements of the one or more sensors, The kit according to claim 67, wherein the elongated shaft comprises a lumen determined to be sized and shaped to receive one or more electrical wires extending between the one or more sensors and the console.

69. A kit for improving systemic perfusion for use with an ECMO machine and an ECMO return cannula in fluid communication, the kit comprising: A flexible extension cannula, The distal end and A long, slender shaft connected to the distal end, Distal region and A proximal region configured to be connected to the outlet of the ECMO return cannula, Multiple pores arranged in the distal region and A flexible extension cannula equipped with, A removable inlet and Equipped with, The distal end of the flexible extension cannula is configured to be advanced within the patient's vascular system via the elongated shaft, and at least a portion of the flexible extension cannula is placed within the detachable introduction device. The detachable introduction device is configured to be positioned within the patient's vascular system such that the proximal end of the detachable introduction device remains outside the patient, and the distal end of the flexible extension cannula is positioned within the patient's vascular system. The detachable introduction device is further configured to be retracted relative to the flexible extension cannula and to be detached from the flexible extension cannula. The ECMO return cannula is configured to be advanced into the patient's vascular system such that the flexible extension cannula extends from a location proximal to the patient's renal blood vessels to a location beyond the patient's renal blood vessels. The flexible extension cannula is configured to transition from a folded inserted state to an expanded, unfolded state that communicates with the blood flow from the ECMO machine, and the flexible extension cannula has a lumen in the expanded state. The blood flow is delivered through the lumen of the flexible extension cannula, via the plurality of pores, to the location beyond the patient's renal blood vessels, thereby improving systemic perfusion.

70. The kit according to claim 69, wherein the elongated shaft is configured such that the blood flow pathway does not pass through the elongated shaft.

71. The kit according to claim 69, wherein the flexible extension cannula further comprises a support portion extending circumferentially along the distal region of the flexible extension cannula, the support portion being configured to transition from a folded delivery state to an extended, unfolded state.

72. The kit according to claim 71, wherein the flexible extension cannula further comprises a plurality of connecting structures extending from the distal end of the flexible extension cannula to the support portion, the plurality of connecting structures being configured to transition from a folded delivery state to an extended unfolded state.

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