SBIR-STTR Award

Counterpulsation with an intra-aortic balloon pump has been widely and successfully used as a short term treatment for both acute and chronic cardiac dysfunction. SCR (Louisville, KY) is developing a novel chronic, implantable counterpulsation device (CPD) to treat late stage HF patients. The CPD is a 32-ml stroke volume polyurethane-lined blood chamber designed to fit comfortably in a subcutaneous pocket on the right anterior chest. The blood pumping chamber is connected to the systemic circulation by a short graft anastomosed to the subclavian artery. The CPD is connected to a small, wearable pneumatic driver via a percutaneous drive line. The CPD fills with blood during native heart systole lowering ventricular workload, and ejects during diastole augmenting myocardial and end-organ perfusion. Previous NIH funding has been received for development of both the blood pumping chamber and the portable driver. The timing of ejection from the pumping chamber was synchronized with EKG signals from epicardial leads, which complicated the surgical procedure. To simplify the implant operation, SCR has developed prototype CPD with integrated subcutaneous leads that are ready for in vivo testing. The objective of this proposal is to determine if the CPD with integrated EKG leads placed in the subcutaneous position will result in a robust, durable signal and allow for ideal timing of device filling and ejection. In Specific Aim 1, standard laparoscopic instruments will be used to place subcutaneous EKG leads. The main goals of this aim are twofold: 1) to demonstrate that we are able to deliver subcutaneous EKG leads and show that they do not migrate, 2) to determine which EKG lead configuration results in the best R wave detection. In Specific Aim 2, we will perform full system implants to evaluate the subcutaneous leads in a chronic bovine model. Lead position will be determined in Specific Aim 1. The data from the subcutaneous EKG leads will be used to time device ejection and compared to simultaneous data obtained from epicardial leads. Treadmill exercise testing will be performed to ensure that motion and muscular activity do not interfere with EKG signaling. Strict criteria for determining if the subcutaneous lead configurations are acceptable are outlined. If successful, in Phase 2 we will perform long-term GLP animal implants with the integrated system in preparation for a clinical investigational device exemption (IDE) study.

Public Health Relevance:
SCR, Inc. (Louisville, KY) is developing a long-term counterpulsation device (CPD) to treat early stage heart failure patients. The CPD has been developed for superficial implantation without the need to enter the chest and a portable pneumatic driver that the patient can carry restores mobility.

Thesaurus Terms:
Acute; Anastomosis; Anastomosis - Action; Animals; Anterior; Blood; Blood Circulation; Bloodstream; Bovine Species; Bypass; Cardiac; Cardiac Failure Congestive; Care, Health; Catheters; Cattle; Cell Communication And Signaling; Cell Signaling; Chest; Chronic; Circulation; Clinical; Clinical Trials; Clinical Trials, Unspecified; Computer Programs; Computer Simulation; Computer Software; Computerized Models; Congestive Heart Failure; Counterpulsation; Data; Detection; Development; Devices; Diastole; Drug Therapy; Dysfunction; Ecg; Ekg; Electrocardiogram; Electrocardiography; Ensure; Exercise Test; Exercise Stress Test; Extremities; Forecast Of Outcome; Functional Disorder; Funding; Goals; Grafting, Heart; Grant; Healthcare; Heart; Heart Decompensation; Heart Failure, Congestive; Heart Transplantation; Heart Failure; Implant; Infection; Infraclavicular; Infraclavicular Region; Infraclavicular Region Structure; Intra-Aortic Balloon Pumping; Intraaortic Balloon Pumping; Intracellular Communication And Signaling; Ischemia; Lead; Left; Limb Structure; Limbs; Lung; Mathematical Model Simulation; Mathematical Models And Simulations; Methods; Modeling; Models, Computer; Motion; Muscle; Muscle Tissue; Myocardial; Myocardial Perfusion; Nih; National Institutes Of Health; National Institutes Of Health (U.S.); Non-Trunk; Operation; Operative Procedures; Operative Surgical Procedures; Organ; Organ Donor; Ostamer; Otomy; Pace Stimulators; Pacemakers; Patients; Pb Element; Pellethane; Performance; Perfusion; Peripheral; Pharmacotherapy; Phase; Physiopathology; Polyisocyanates; Polyurethanes; Position; Positioning Attribute; Preparation; Prognosis; Pump; Qol; Quality Of Life; Research Resources; Resources; Respiratory System, Lung; Reticuloendothelial System, Blood; Right-On; Sbir; Sbirs (R43/44); Strnty; Safety; Signal Transduction; Signal Transduction Systems; Signaling; Simulation, Computer Based; Small Business Innovation Research; Small Business Innovation Research Grant; Software; Staging; Sternotomy; Stimulators, Electrical, Pace; Stroke Volume; Structure Of Subclavian Artery; Subclavian Artery; Surgical; Surgical Interventions; Surgical Procedure; Surgical Incisions; System; System, Loinc Axis 4; Systole; Testing; Thorace; Thoracic; Thorax; Time; Time Study; Transplantation, Cardiac; United States National Institutes Of Health; Vascular Graft; Ventricular; Work Load; Workload; Base; Biological Signal Transduction; Blood Pump; Bovid; Bovine; Cardiac Failure; Cardiac Graft; Clinical Investigation; Computational Modeling; Computational Models; Computational Simulation; Computer Based Models; Computer Program/Software; Computerized Modeling; Computerized Simulation; Cost; Cow; Design; Designing; Effective Therapy; Heart Transplant; Heavy Metal Pb; Heavy Metal Lead; Implantation; In Silico; In Vivo; Incision; Instrument; Interest; Novel; Outcome Forecast; Pathophysiology; Preclinical Study; Prototype; Public Health Relevance; Pulmonary; Subcutaneous; Surgery; Ventricular Assist Device; Virtual Simulation

Heart failure (HF) remains one of the largest unsolved problems in health care today and continues to increase in incidence and cost ($34.8 billion in US in 2008). Prognosis remains limited especially in patients with advanced heart failure. Transplantation is often the best option for patients with advanced HF whose hearts are not recoverable but is limited by many factors, primarily the small number of available donor hearts (<2500/yr in US). Use of current mechanical circulatory support (MCS) devices, though increasing, has also been limited due to the need for a major operation, restriction to Class IV patients, prolonged convalescence, and cost (over $100,000 US for the device itself). We have developed a novel MCS device (Symphony) that works synchronously with the heart, can be placed with a minor operation, and takes advantage of the proven benefits of counterpulsation. Symphony provides partial circulatory support to augment (not replace) native heart function. Recent clinical studies have provided strong evidence for the benefits of partial support. Also, experimental data strongly supports the benefits of partial support rather than complete unloading of the heart to promote myocardial recovery. The Symphony device is placed through an 8-cm infraclavicular incision similar to that used for placement of a permanent pacemaker. A short graft is sewn to the subclavian artery, connected to the pump, and then positioned superficial to the pectoralis muscle. Symphony is timed with the EKG to fill during systole and eject during diastole. Recent work in a Phase 1 study demonstrated subcutaneous EKG leads were as effective as epicardial leads for QRS detection and triggering. In this phase II study, we will complete development of the subcutaneous EKG lead system with integration to the Symphony device and lightweight, portable driver, and demonstrate efficacy, safety, and reliability of all system components. The development of a device that works synchronously with the heart, provides partial support (thereby promoting recovery), and can be placed with a "pacemaker pocket" operative approach may have a significant impact in expanding the role of circulatory support in the treatment of HF patients. The additional advantage of low cost (due to simplicity of design and a limited operative approach) may further expand the use of mechanical support with this device to currently large, unrealized, global markets.

Public Health Relevance:
Heart failure is a major and growing health care concern for which there are limited treatment options in advanced stages. A novel circulatory support device is being developed that works synchronously with the heart (thereby promoting recovery), can be placed without a major operation, and uses a proven mechanism of circulatory support (counterpulsation). This device may significantly increase the use of circulatory support for patients with advanced heart failure and possibly lead to earlier use in less ill patients with the potential for myocardial recovery.

Public Health Relevance Statement:
Heart failure is a major and growing health care concern for which there are limited treatment options in advanced stages. A novel circulatory support device is being developed that works synchronously with the heart (thereby promoting recovery), can be placed without a major operation, and uses a proven mechanism of circulatory support (counterpulsation). This device may significantly increase the use of circulatory support for patients with advanced heart failure and possibly lead to earlier use in less ill patients with the potential for myocardial recovery.

Project Terms:
Adoption; biomaterial compatibility; Blood Circulation; Bypass; Cardiovascular system; Caring; Cattle; Chest; China; Chronic; Clinical; clinical practice; Clinical Research; Clinical Trials; commercialization; computerized data processing; conditioning; Convalescence; cost; Counterpulsation; Data; design; Detection; Development; Device Designs; Devices; Diastole; Early treatment; Electrocardiogram; Engineering; Exercise; Failure (biologic function); Fatigue; Fracture; Goals; Government Agencies; Healthcare; Heart; Heart failure; heart function; Heart Transplantation; hemodynamics; Implant; Implantation procedure; improved; Incidence; India; industry partner; Infection; Infraclavicular region structure; innovation; Institutes; interest; Intra-Aortic Balloon Pumping; Lead; Legal patent; Lung; Marketing; Mechanics; Medical; Methods; Metric; migration; Mind; miniaturize; Minor; Modeling; Morphologic artifacts; Motion; Myocardial; novel; operation; Operative Surgical Procedures; Organ Donor; Outcome; outcome forecast; Pacemakers; patient population; Patients; Pectoralis Muscles; Perfusion; Phase; phase 1 study; phase 2 study; Positioning Attribute; Predictive Value; product development; programs; prototype; Pump; Quality of life; Recovery; Research Personnel; research study; Resources; Role; Safety; Sensitivity and Specificity; Signal Transduction; Staging; Sternotomy; Stroke Volume; Structure of subclavian artery; Study models; subcutaneous; Support System; Surface; Surgical incisions; System; Systole; Testing; Therapeutic; Time; Transplantation; Ventricular; Work; Workload