SBIR-STTR Award

Left ventricular assist device (LVAD) support allows the neonate with congenital heart disease or cardiomyopathy to grow to a larger body weight that is more feasible for complex surgical correction or heart transplant. A paracorporeal LVAD, the Berlin heart ExCor, is FDA-approved for pediatric application. Although this device is outside the body, the outflow graft may still create coronary artery/heart compression. Our ultimate goal is to develop a less invasive and dependable LVAD system for the neonate. The enabling technology will be a small (16-18 Fr) double lumen cannula (DLC), which is inserted from the apex though the LV and aortic valve into the aorta with the drainage lumen opening in the LV and the infusion lumen in the aorta. Coupled with a blood pump, blood is withdrawn from the LV and infused into the aorta to unload the LV though a single cannulation. This DLC-based LVAD: 1) has only one apex cannulation, avoiding heart/coronary artery compression, 2) has a much smaller apex cannulation, eliminating cardiopulmonary bypass, 3) requires a less traumatic left thoracotomy, replacing traumatic medium sternotomy, and 4) has a flexible configuration, allowing a bigger paracorporeal pump for stronger performance and the addition of a gas exchanger for cyanotic heart diseases. Our DLC-based LVAD is much simpler, less invasive, more powerful, and very suitable for neonate application. Our objective in this Phase I SBIR is to develop and fabricate a working prototype of a DLC assembly for a neonate LVAD and to test the prototype's performance in neonate sheep. Our hypothesis is that this new DLC, coupled with a commercial blood pump, will provide total LV support and save the life of sick neonate. It will bridge the patient to recovery, transplant, or further advanced heart surgery. Specific Aim 1:To develop a new TransApical to Aorta (TAA) DLC assembly. A. To design and fabricate a new working prototype of a TAA DLC for a neonate LVAD. The DLC main body outer wall will be constructed with wire reinforced polyurethane. The inner infusion lumen will use an eccentric membrane sleeve. The DLC membrane sleeve infusion lumen extends out of DLC main body to the extension infusion cannula (EIC). The EIC will be reinforced by stainless steel wires across the aortic valve into the ascending aorta. A sewing plate will be designed for sewing the DLC onto the apex, preventing TAA DLC dislodgement. B. Bench testing of the TAA DLC assembly. Bench testing will be done in an ex vivo circuit to measure DLC flow performance. Specific Aim 2: To test our prototype TAA DLC for ease of deployment and 6 hr. in vivo performance. The TAA DLC prototype will be coupled with a CentriMag pump to form a TAA LVAD system. The in vivo new born lamb experiments (n=5) will test the DLC for TAA deployment and in vivo performance. The 16 Fr DLC- based TAA LVAD will pump the blood at a flow rate up to 1 L/min against 200 mmHg ?P. Animal testing results will be used to optimize the TAA DLC design for best performance/reliability for the Phase II grant. Upon this SBIR grant completion, the commercialized TAA DLC will provide a less invasive neonate LVAD.

Thesaurus Terms:
Acute;Adult;American;Animal Testing;Anticoagulation;Aorta;Aortic Valve;Applications Grants;Area;Artificial Lung;Ascending Aorta;Base;Berlin;Biomedical Engineering;Blood;Blood Pump;Body Weight;Businesses;Cannulas;Cannulations;Carbon Dioxide;Cardiac;Cardiac Surgery Procedures;Cardiogenic Shock;Cardiomyopathies;Cardiopulmonary Bypass;Chest;Childhood;Complex;Congenital Heart Disorder;Coronary Artery;Coupled;Deposition;Design;Development;Devices;Diaphragm (Anatomy);Drainage Procedure;Excision;Experience;Fda Approved;Fibrin;Flexibility;Gases;Goals;Grant;Heart;Heart Diseases;Heart Failure;Heart Transplantation;Hemoglobin;Improved;In Vivo;Infusion Procedures;Kentucky;Laboratory Animal Production And Facilities;Left;Life;Liquid Substance;Lung;Measurement;Measures;Membrane;Morbidity - Disease Rate;Mortality Vital Statistics;Multidisciplinary;Neonatal;Neonate;Novel;Operative Surgical Procedures;Patients;Performance;Phase;Plasma;Platelet Activation;Play;Polyurethanes;Prevent;Prototype;Public Health Relevance;Pump;Recovery;Research And Development;Research Study;Resistance;Respiratory;Sheep;Small Business Innovation Research Grant;Stainless Steel;Sternotomy;Surgeon;System;Technology;Test Result;Testing;Thoracotomy;Thrombelastography;Total Artificial Heart;Transplantation;Universities;Ventricular;Ventricular Assist Device;Work;

Left ventricular assist device (LVAD) support allows the neonate with congenital heart disease or cardiomyopathy to grow to a larger body weight that is more feasible for complex surgical correction or heart transplant. The Berlin Heart ExCOR, is FDA-approved for pediatric LVAD application. Although this device is outside the body, the outflow graft may still create coronary artery/heart compression. Our ultimate goal is to develop a less invasive and dependable LVAD system for the neonate as well as older pediatric patients. The enabling technology is a double lumen cannula (DLC), which is inserted from the apex into the aorta. Coupled with an existing blood pump, this DLC withdraws blood from the LV and delivers blood into the aorta, unloading the LV. Our DLC-based LVAD only requires a one site, less invasive apex cannulation. The advantages are: 1) no outflow graft and associated heart/coronary artery compression; 2) no need of cardiopulmonary bypass and associated blood transfusion; 3) reserves more invasive sternotomy for future complex heart surgery. This transapical to aorta (TAA) DLC enables a high performance paracorporeal/ extracorporeal LVAD and allows addition of a gas exchanger for cyanotic heart disease. Our Phase I study proved that the TAA DLC-based neonate LVAD system was very easy to implant via a small left thoracotomy and efficiently unloaded the LV for 6 hours with no increase in free hemoglobin and no decrease in hemoglobin and platelet counts. Phase II SBIR objective: Based on the Phase I results, we will optimize the design and fabricate a final commercial quality TAA DLC prototype for even smaller neonate application and for 5 day survival lamb studies. Specific Aim 1: To design, fabricate, and bench-test the high efficiency, commercial quality TAA DLC prototype for smaller neonate application and for 5 day survival in vivo lamb studies. The TAA DLC will be made of one piece reinforced polyurethane. Computational fluid dynamics will be used to optimize the DLC design. A DLC anchoring system will be also developed to secure TAA DLC on apex and chest wall for long-term ambulatory use. A 13 Fr/10 Fr TAA DLC will be developed for 2-4 kg neonate lamb acute study and a 19 Fr/15 Fr TAA DLC will developed for 4 week old lamb (20 kg) survival study. The final prototype will be tested for performance, reliability, and hemolysis. Thirty day durability will be tested in 37% glycerin. Specific Aim 2: To test new 13/10 Fr TAA DLC-based LVAD in 2- 4 kg neonate lamb (n=5). This 6 hour study is designed to prove TAA DLC suitable for clinical neonate LVAD application. We will investigate ease of TAA deployment and in vivo performance, as well as potential aortic valve obstruction by extension infusion cannula. Specific Aim 3: To test the TAA DLC prototype for 5 days LVAD application in 4 weeks old neonate lamb (n=5). The 4 week old lamb is still considered a neonate but almost fully weaned, allowing us to perform 5 day survival study. This in vivo study will test performance, reliability, durability, and biocompatibility. Upon this SBIR grant completion, the commercialized TAA DLC will provide a less invasive neonate LVAD.

Public Health Relevance Statement:
We are proposing to develop a simple, less invasive double lumen cannula-based left ventricular assist device (LVAD) for the neonate as well as older pediatric patients. The enabling technology is the novel double lumen cannula which is coupled with a blood pump to form a LVAD system to provide total left ventricular support, thereby saving the lives of sick neonates and older pediatric patients. This neonate LVAD system will bridge the patient to recovery, transplant, or further advanced heart surgery.

Project Terms:
Acute; Adult; Animals; Aorta; aortic valve; Apical; artificial lung; base; Berlin; biomaterial compatibility; Biotechnology; Blood; Blood Circulation; blood pump; Blood Transfusion; Body Weight; Cannulas; Cannulations; Carbon Dioxide; Cardiac; Cardiac Surgery procedures; Cardiogenic Shock; Cardiomyopathies; Cardiopulmonary Bypass; Chest; Chest wall structure; Childhood; Clinical; Complex; congenital heart disorder; Coronary artery; Coupled; design; Development; Devices; Eating; Engineering; Ensure; Enteral Nutrition; Excision; experience; falls; FDA approved; feeding; Food; Future; Gases; Glycerol; Goals; Grant; Heart; Heart Diseases; Heart failure; Heart Transplantation; Hemoglobin; Hemolysis; Hemorrhage; Hour; Implant; implantation; in vivo; Incidence; Infection; Infusion procedures; Kentucky; Laboratory Animal Production and Facilities; Left; left ventricular assist device; Liquid substance; Lung; Mediastinal; Milk; Morbidity - disease rate; mortality; multidisciplinary; Neonatal; neonate; Newborn Infant; novel; Obstruction; Operative Surgical Procedures; Patients; pediatric patients; Pediatrics; Performance; performance tests; Phase; phase 1 study; Platelet Count measurement; Polyurethanes; Positioning Attribute; prototype; Publications; Recovery; research and development; Research Support; respiratory; Safety; Savings; Scientist; Secure; Sedation procedure; Site; Small Business Innovation Research Grant; Solid; Sternotomy; Surgeon; System; Technology; Testing; Thoracotomy; Transplantation; Universities; Ventricular; Weaning; Weight