SBIR-STTR Award

Extracorporeal membrane oxygenation (ECMO) use continues to increase as a supportive measure for cardio-respiratory failure. Pediatric patients with severe acute left ventricular (LV) systolic dysfunction are often supported with venoarterial (VA) ECMO as a short-term bridge to recovery, transplant or a ventricular assist device (VAD). Although this often provides the much needed temporary gas exchange and increase in cardiac output to all important end organs, lack of egress of blood from the LV can lead to over-distension and elevated LV end diastolic pressure (LVEDP), which reduces myocardial oxygen delivery and recovery. The risk of progressive increase in left-sided filling pressures needs to be monitored closely to avoid the deleterious effects of left-heart distention. Left ventricular distention in patients with profoundly reduced left ventricular contractility is a major risk factor for poor myocardial recovery and failure to wean from ECMO. Mechanical decompression of the left-heart during ECMO is sometimes required to address ventricular distention and is often a life-saving intervention. For patients who do not have open access to the heart for surgical decompression (i.e. post-operative cardiac patients), left ventricular decompression is most commonly accomplished by percutaneous transseptal puncture followed by either septostomy or placement of a drain or device to keep the atrial communication patent. Due to the lack of a FDA-approved devices for this indication, all options of decompression represent off-label use of devices not specifically designed for this intervention The goal of this project is to design, test, and produce a line of pediatric and adult ventricular assist catheters (VAC) that can be used for short term left heart decompression in patients on VA ECMO for acute severe LV systolic dysfunction. The MC3 VAC line will include lengths and diameters to cover the entire spectrum of sizes required for the pediatric population for both low flow left heart decompression and high flow total ventricular assist. The largest size catheters will also support the adult patient so the line will be designed to truly match the entire patient spectrum. Phase I of the study will include capturing detailed design inputs for the population, by analyzing pediatric patient data from clinical cases at The University of Michigan. User requirements will be translated into design inputs/outputs by MC3's team of experienced cannula design engineers, who have designed several, commercially-successful cannula and introducer systems. Feasibility will be established by evaluating performance of the VAC against specific criteria unique to usage in the pediatric application. Phase II funding, if granted, will be sufficient to complete verification/validation testing, transfer to manufacture, and FDA and CE mark submissions. We have assembled a synergistic team of experts, clinicians, marketers, manufacturers and engineers who are uniquely qualified to carry out the proposed work.

Public Health Relevance Statement:
NARRATIVE Extracorporeal Membrane Oxygenation (ECMO) has become a widely accepted means to provide short-term circulatory support for pediatric and adult patients suffering from acute cardiac failure. The biggest problem for cardiac ECMO is that complications can arise when pressure builds in the heart, and unloading or decompression of the left side is frequently required. The goal of this project is to develop a pediatric and adult line of cardiac catheters that can be used to decompress the left heart in patients on ECMO, as well as a full circulatory assist catheter device if indicated. Currently, there is no such catheter solely approved for this use in pediatrics, and options are limited for adults.

Project Terms:
Acute; Address; Adult; Animals; Assisted Circulation; Berlin; Blood; Caliber; Cannulas; Cardiac; Cardiac Catheterization Procedures; Cardiac Output; Cardiopulmonary; Caring; Catheters; Child; Childhood; Clinical; Clinical Data; Communication; Critical Illness; Data; design; Device Designs; Devices; Diastolic blood pressure; Distant; Engineering; engineering design; Ensure; experience; Extracorporeal Membrane Oxygenation; Failure; FDA approved; Functional disorder; Funding; Future; Gases; Goals; Grant; Growth; Heart; Heart Atrium; Heart failure; Hemolysis; Hypertension; improved; indexing; Infant; Intervention; Label; Lead; Left; Left Ventricular Dysfunction; Legal patent; Length; Life; Literature; Magnetic Resonance Imaging; Manufacturer Name; manufacturing facility; Marketing; Measures; Mechanics; medical specialties; meetings; member; Methods; Michigan; migration; Monitor; mortality; Myocardial; Operative Surgical Procedures; Organ; Output; Oxygen; Patients; pediatric patients; Pediatrics; Performance; Phase; phase 1 study; Population; Positioning Attribute; Postoperative Period; pressure; Price; Procedures; prototype; Puncture procedure; Qualifying; Recovery; Registries; Respiratory Failure; Risk; Risk Factors; Safety; Side; success; Surgical Decompression; System; Technology; Testing; therapy design; Translating; Transplantation; Universities; Ventricular; ventricular assist device; verification and validation; Weaning; Work

Extracorporeal membrane oxygenation (ECMO) use continues to increase as a supportive measure for cardio-respiratory failure. Pediatric patients with severe, acute left ventricular (LV) systolic dysfunction are often supported with venoarterial (VA) ECMO as a short-term bridge to recovery, transplant or a ventricular assist device (VAD). ECMO provides temporary gas exchange and increased cardiac output to end organs. Lack of egress of blood from the LV can lead to over-distension and elevated LV end diastolic pressure (LVEDP), which reduces myocardial oxygen delivery and recovery. The risk of progressive increase in left- sided filling pressures needs to be monitored closely to avoid the deleterious effects of left-heart distention. Left ventricular distention in patients with profoundly reduced left ventricular contractility is a major risk factor for poor myocardial recovery and failure to wean from ECMO. Mechanical decompression of the left-heart during ECMO is sometimes required, as a life-saving intervention. For patients who do not have open access to the heart for surgical decompression (i.e. post-operative cardiac patients), left ventricular decompression is most commonly accomplished by percutaneous transseptal puncture followed by either septostomy, placement of a drain device to keep the atrial communication patent, and placement of a pVAD such as Impella 2.5 which is only available for adults, is hemolytic, and is extremely expensive. Due to the lack of an FDA-approved device for this indication, options for decompression represent off-label use, and none of these devices is designed for pediatrics. The goal of this project is to design, test, and produce a line of pediatric and adult left heart decompression catheters suitable to be used in patients on VA ECMO for acute, severe LV systolic dysfunction. The MC3 InterSept™ catheter line will include lengths and diameters to cover the entire spectrum of sizes required for the pediatric population from 2 kg to fully-grown patients, for both low flow left heart decompression and high flow total ventricular assist. Phase I captured detailed design inputs for the population by analyzing pediatric CT scan data from clinical cases at The University of Michigan. User requirements were translated into design inputs/outputs by MC3's team of experienced cannula design engineers. Feasibility was established by evaluating performance of the InterSept against specific criteria unique to use in the pediatric application. With Phase II funding, the full range of InterSept will be optimized, verification/validation testing will be completed, the design will be transferred to in-house MC3 manufacturing, and FDA and CE mark submissions will be filed using the ECMO pathway in the US and the Class 3 CE Mark pathway in accordance with the new European Medical Device Regulation. We have assembled a synergistic team of experts, clinicians, marketers, manufacturers and engineers who are uniquely qualified to carry out the proposed work.

Public Health Relevance Statement:
NARRATIVE Extracorporeal Membrane Oxygenation (ECMO) is increasing and has become a widely accepted means to provide support for pediatric and adult patients suffering from acute cardiac and/or pulmonary failure. The biggest problem for cardiac ECMO is that complications can arise when pressure builds in the heart, and unloading or decompression of the left side is frequently required. The goal of this project is to develop a pediatric and adult line of cardiac catheters that can be used to decompress the left heart in patients on ECMO, with potential to be used as a full circulatory assist catheter if indicated. Currently, there is no such catheter solely approved for this use in pediatrics, and options are limited for adults.

Project Terms:
Acute; Adolescent; Adult; aged; Assisted Circulation; Berlin; biological systems; Blood; Blood Vessels; Caliber; Cannulas; Cardiac; Cardiac Output; Cardiopulmonary; Caring; Catheters; Child; Childhood; Clinical; Clinical Data; Communication; cost; Critical Illness; Cyclic GMP; design; Development; Devices; Diastolic blood pressure; Engineering; engineering design; European; experience; Extracorporeal Membrane Oxygenation; Failure; FDA approved; Functional disorder; Funding; Gases; Goals; Heart; Heart Atrium; Heart failure; Hemolysis; Hypertension; improved; in vivo; Infant; Injury; Intervention; Lead; Left; Legal patent; Length; Life; Literature; Manufacturer Name; Measures; Mechanics; Medical Device; medical specialties; member; Methods; Michigan; Molds; Monitor; mortality; Myocardial; off-label use; off-patent; Organ; Output; Oxygen; Pathway interactions; Patients; pediatric patients; Pediatrics; Performance; Phase; Population; Population Analysis; Postoperative Period; pressure; Price; Puncture procedure; Recovery; Registries; Regulation; Respiratory Failure; Risk; Risk Factors; Safety; Savings; Side; success; Surgical Decompression; System; Technology; Testing; thrombogenesis; Translating; Transplantation; Universities; Ventricular; ventricular assist device; verification and validation; Weaning; Work; X-Ray Computed Tomography