SBIR-STTR Award

Development of Percutaneous DLC for Total Cavo-Pulmonary Assistance
Award last edited on: 11/6/2019

Sponsored Program
STTR
Awarding Agency
NIH : NHLBI
Total Award Amount
$1,175,843
Award Phase
2
Solicitation Topic Code
837
Principal Investigator
Stephen R Topaz

Company Information

W-Z Biotech LLC

1224 Raeford Lane
Lexington, KY 40513
   (859) 494-4134
   dwang.tx@gmail.com
   N/A

Research Institution

University of Kentucky

Phase I

Contract Number: 1R41HL107062-01A1
Start Date: 6/15/2011    Completed: 5/31/2012
Phase I year
2011
Phase I Amount
$175,322
The Fontan procedure is currently standard care for patients with complex single ventricle congenital heart defects. The Fontan procedure involves the creation of a cavopulmonary (CP) shunt connecting the inferior and superior vena cava (IVC and SVC) directly to the right pulmonary artery (RPA), diverting total venous return from the IVC/SVC directly to the PA without entering the right atrium (RA) and right ventricle (RV). The Fontan procedure results in a blood flow pattern of a passively filled pulmonary circulation and a single ventricle to pump blood to the systemic circulation. Although it has improved thousands of patients'quality of life by increasing arterial O2 saturation, the mortality is reported at 29.1%1. Patients with a failing Fontan follow a bimodal distribution with some failing acutely in the early post-operative period and others are failing years later2, 3. Cavopulmonary assistance (CPA) is highly desired to effectively pump venous blood through the Fontan connection to the pulmonary artery and to reverse the pathophysiology of the failing Fontan circulation. However, there is currently no specific device available for CPA. Our objective in this Phase I STTR is to develop and fabricate a working prototype of a percutaneous double lumen cannula (DLC) for CPA and to test this prototype in our new failing Fontan sheep model. Our ultimate goal is to develop a CPA system that avoids the need for an open surgical procedure or the use of cardiopulmonary bypass (CPB). The enabling technology will be a percutaneous DLC that will drain venous blood from both the IVC and SVC simultaneously and infuse blood directly into the pulmonary artery. Our Specific Aims are: 1) to develop and fabricate a working prototype of a percutaneous DLC to assist failing Fontan circulation, and 2) to test our prototype CPA DLC in our improved failing Fontan sheep model. Our proposed cannula-based CPA will be a ""game changer"" in the management of failing Fontan physiology.

Public Health Relevance:
We are proposing to develop a percutaneous Cavopulmonary assistance system to bridge the patients with failing Fontan circulation for recovery, reconstructive surgery and heart transplantation.

Thesaurus Terms:
Abscission;Absence Of Interventricular Septum;Acute;Anastomosis;Anastomosis - Action;Anatomic;Anatomical Sciences;Anatomy;Area;Blood;Blood Circulation;Blood Pressure;Blood Reticuloendothelial System;Blood Flow;Bloodstream;Businesses;Co2;Cannulas;Carbon Dioxide;Carbonic Anhydride;Cardiac;Cardiac Abnormalities;Cardiac Malformation;Cardiac Output;Cardiac Transplantation;Cardiac Defect;Cardiopulmonary;Cardiopulmonary Bypass;Cavopulmonary Anastomosis;Cavopulmonary Shunt;Central Venous Pressure;Childhood;Chronic;Circulation;Clinical;Common Ventricle;Complex;Congenital Cardiac Defects;Congenital Heart Defects;Cor Triloculare Biatriatum;Development;Development And Research;Devices;Drainage;Drainage Procedure;Dysfunction;Engineering;Excision;Extirpation;Fontan Operation;Fontan Procedure;Functional Disorder;Goals;Heart;Heart Abnormalities;Heart Grafting;Heart Malformation;Heart Transplantation;Heart-Lung Bypass;Hour;Inferior;Infusion;Infusion Procedures;Kentucky;Loinc Axis 4 System;Laboratory Animal Production And Facilities;Low Cardiac Output;Lung;Lung Respiratory System;Membrane;Modeling;Monitor;Morbidity;Morbidity - Disease Rate;Mortality;Mortality Vital Statistics;Operative Procedures;Operative Surgical Procedures;Ovis;Patients;Pattern;Perfusion;Phase;Physiology;Physiopathology;Post-Operative;Postoperative;Postoperative Period;Publications;Pulmonary Artery;Pulmonary Circulation;Pulmonary Vascular Resistance;Pulmonary Artery Structure;Pump;Qol;Quality Of Life;R &D;R&D;Reconstructive Surgical Procedures;Recovery;Removal;Reporting;Research Animal Facility;Research Support;Respiratory Circulation;Right Atrium;Right Cardiac Bypass;Right Heart Bypass;Right Ventricles;Right Atrial Structure;Right Pulmonary Artery;Right Ventricular Structure;Sttr;Scientific Publication;Sheep;Side;Simulate;Small Business Technology Transfer Research;Superior Vena Cava;Superior Vena Cava Structure;Surgeon;Surgical;Surgical Interventions;Surgical Procedure;Surgical Removal;System;Technology;Testing;Transplantation;Universities;Venous;Work;Artificial Lung;Base;Blood Pump;Cardiac Graft;Commercialization;Design;Designing;Developmental;Experience;Flexibility;Flexible;Heart Bypass;Heart Defect;Heart Output;Heart Transplant;Improved;In Vivo;Membrane Structure;Multidisciplinary;Pathophysiology;Patient Population;Pediatric;Pressure;Prototype;Pulmonary;Reconstructive Surgery;Research And Development;Resection;Respiratory;Single Functional Ventricle;Single Ventricle;Standard Care;Standard Treatment;Surgery;Transplant;Univentricular Heart

Phase II

Contract Number: 2R44HL129490-02A1
Start Date: 8/15/2016    Completed: 7/31/2018
Phase II year
2016
(last award dollars: 2017)
Phase II Amount
$1,000,521

The Fontan procedure or total cavopulmonary connection (TCPC) is a standard palliative surgery for patients with complex single ventricle congenital heart anomalies. TCPC connects the inferior and superior vena cava (IVC and SVC) directly to the right pulmonary artery, bypassing the heart. The single ventricle is then reserved for pumping oxygenated blood to the systemic circulation. The Fontan procedure has benefited thousands of patients, but the Fontan circulation fails years later with relatively high mortality. The failing Fontan circulation causes end organ dysfunction due to venous blood congestion from elevated central venous pressure and low arterial blood perfusion from low cardiac output. The only effective option for the failing Fontan patient is heart transplant, but most of these patients are too sick to be transplant candidates. Cavopulmonary assist (CPA) is needed to pump venous blood from SVC/IVC through the Fontan connection to reverse failing Fontan pathophysiology. Our ultimate goal is to create a convenient and secure connection between the TCPC and the blood pump, establishing an ambulatory percutaneous CPA system. Our enabling technology is one of the world's most complex double lumen cannula (DLC). Through only one percutaneous venous cannulation, this DLC can easily connect the TCPC to a commercial blood pump without major surgery. This CPA system will bridge the failing Fontan patient to: 1) heart transplant, 2) recovery, and/or 3) further reconstructive heart surgery. In ou phase I study, the working prototype demonstrated up to 4.5 l/min blood flow in our sheep model and completely reversed failing Fontan circulation (n=5), achieving total CPA. In this Phase II SBIR, we will optimize the design based on our Phase I results, and fabricate a final commercial quality CPA DLC prototype for bench test and 5 day survival in vivo studies. Specific Aim 1: To design and fabricate a percutaneous DLC for ambulatory CPA application. Two thin membrane umbrellas are designed on the DLC to prevent infusion flow recirculation, ensuring efficient and reliable performance. These umbrellas do not block the blood flow from SVC and IVC to pulmonary artery, guaranteeing safety if the CPA system malfunctions. Two infusion openings guide separate blood flow to each umbrella, eliminating blood stagnancy and associated thrombosis formation. Particle image velocimetry (PIV) validated CFD will be used to optimize the design for maximum performance and minimal thrombotic potential. Specific Aim 2: To test the CPA DLC prototype in a simulated mock loop bench test. Bench testing will include performance/reliability evaluation, one month durability test, and PIV flow study. Specific Aim 3: To test the CPA DLC prototype in our TCPC sheep model. Short term in vivo studies (N=5) will test CPA DLC feasibility, performance, and reliability. Long term 5 day in vivo studies (N=8) will test performance, reliability, durability, and biocompatibility. Although the CPA DLC market is small, the impact on the patients that need CPA is significant.

Public Health Relevance Statement:


Public Health Relevance:
We are proposing to develop a percutaneous cavo-pulmonary assist system to bridge the patients with failing Fontan circulation for recovery, reconstructive surgery and heart transplantation.

NIH Spending Category:
Assistive Technology; Bioengineering; Cardiovascular; Congenital Heart Disease; Congenital Structural Anomalies; Heart Disease; Lung; Organ Transplantation; Pediatric; Perinatal Period - Conditions Originating in Perinatal Period; Rare Diseases; Transplantation

Project Terms:
Anastomosis - action; Animals; artificial lung; base; biomaterial compatibility; Biotechnology; Blood; Blood Circulation; Blood flow; blood perfusion; blood pump; Cannulas; Cannulations; Carbon Dioxide; Cardiac; Cardiac Surgery procedures; Cardiopulmonary Bypass; Cattle; Central venous pressure; Childhood; Clinical; commercialization; Common Ventricle; Complex; congenital heart disorder; design; Deterioration; Development; Devices; Drainage procedure; Engineering; Ensure; Evaluation; Excision; experience; Fontan Procedure; Functional disorder; Future; Glycerol; Goals; Heart; Heart Transplantation; Hemolysis; Hypoxia; Image; In Vitro; in vivo; Inferior; Infusion procedures; Kentucky; Laboratory Animal Production and Facilities; Life; Liquid substance; Low Cardiac Output; Lung; Marketing; Membrane; Modeling; mortality; Operative Surgical Procedures; Organ; Palliative Surgery; particle; Patients; Performance; performance tests; Phase; phase 1 study; Polyurethanes; prevent; Procedures; prototype; public health relevance; Publications; Pulmonary artery structure; Pulmonary Circulation; Pulmonary Vascular Resistance; Pump; Reconstructive Surgical Procedures; Recovery; research and development; Research Support; respiratory; Safety; Scientist; Secure; Sheep; simulation; Small Business Innovation Research Grant; Superior vena cava structure; Surgeon; System; Technology; Testing; Thrombosis; Transplantation; Universities; Validation; Velocimetries; Venous; Venous system; Ventricular; Work