SBIR-STTR Award

The overall objective of this proposed program is the commercialization of an advanced intraventricular cardiac assist system for cardiac unloading and recovery. This type of ventricular assist device (VAD) will provide the optimal support for recovery for acute heart failure patients, and may be useful for a select group of chronic heart failure patients supported on VADs. Phase I of the program will demonstrate the feasibility of an innovative VAD system designed to permit rapid insertion and to provide hemodynamic tunability for optimizing ventricular recovery. Key design milestones will include prototype construction, in vitro characterization and in vivo feasibility testing. Following the successful completion of the Phase I studies, Phase 2 of the program will focus on further developing the system for extended use and characterizing its use for ventricular recovery. The Phase 2 results will permit a timely commercial introduction of this technology. This device's ability to tailor support from complete decompression, to gradual reloading, and finally to normalization of the myocyte stress environment will provide heart failure patients the best chance for cardiac recovery.

Public Health Relevance:
A growing trend in mechanical circulatory support is the application of ventricular assist devices (VADs) to bridge-to-recovery (BTR), where the goal is to recover the native heart. LVADs provide profound LV volume and pressure unloading while simultaneously restoring both coronary and systemic blood flow. In cases of acute heart failure, it is frequently observed that the rested but well perfused myocardium experiences healing and ultimately a restoration of function. As a result, a strong clinical need exists for a VAD that is easy to implant and tunable to optimize the hemodynamic conditions for recovery. The innovative VAD system proposed here will permit a rapid insertion along with hemodynamic tunabilty to optimize the conditions for recovery. With the proposed device, patients will have mechanical support tailored to their evolving needs: complete decompression early on, then gradual reloading of the heart, and finally normalization of the myocyte stress environment after cardiac recovery. The proposed system would be directly applicable to acute heart failure patients (e.g. those suffering from cardiogenic shock subsequent to acute myocardial infarction, myocarditis, or open heart surgery), which includes approximately 100,000 patients per year in the U.S. It may also promote myocardial recovery in those chronic heart failure patients who require VAD support.

Public Health Relevance Statement:
PROJECT NARRATIVE A growing trend in mechanical circulatory support is the application of ventricular assist devices (VADs) to bridge-to-recovery (BTR), where the goal is to recover the native heart. LVADs provide profound LV volume and pressure unloading while simultaneously restoring both coronary and systemic blood flow. In cases of acute heart failure, it is frequently observed that the rested but well perfused myocardium experiences healing and ultimately a restoration of function. As a result, a strong clinical need exists for a VAD that is easy to implant and tunable to optimize the hemodynamic conditions for recovery. The innovative VAD system proposed here will permit a rapid insertion along with hemodynamic tunabilty to optimize the conditions for recovery. With the proposed device, patients will have mechanical support tailored to their evolving needs: complete decompression early on, then gradual reloading of the heart, and finally normalization of the myocyte stress environment after cardiac recovery. The proposed system would be directly applicable to acute heart failure patients (e.g. those suffering from cardiogenic shock subsequent to acute myocardial infarction, myocarditis, or open heart surgery), which includes approximately 100,000 patients per year in the U.S. It may also promote myocardial recovery in those chronic heart failure patients who require VAD support.

Project Terms:
Acute; Acute myocardial infarct; Acute myocardial infarction; Address; Anastomosis; Anastomosis - action; Aortic Valve; Aortic valve structure; Back; Blood; Blood flow; Cannulas; Cardiac; Cardiac Surgery; Cardiac Surgery procedures; Cardiac Surgical Procedures; Cardiogenic Shock; Chronic; Clinical; Clinical Trials, Phase I; Coronary; Development; Device Removal; Devices; Diastole; Dorsum; ECG; EKG; Early-Stage Clinical Trials; Electrocardiogram; Electrocardiography; Engineering; Engineerings; Environment; Extracorporeal Circulation; Extravasation; Goals; Healed; Heart; Heart failure; Hemolysis; Implant; In Vitro; Intraventricular; Leakage; Left; Liquid substance; Measurement; Mechanics; Modeling; Muscle Cells; Muscle Cells, Mature; Muscle, Cardiac; Muscle, Heart; Myocardial; Myocarditis; Myocardium; Myocytes; Operation; Operative Procedures; Operative Surgical Procedures; Patients; Phase; Phase 1 Clinical Trials; Phase I Clinical Trials; Phase I Study; Population; Pressure; Pressure- physical agent; Programs (PT); Programs [Publication Type]; Pump; Recovery; Rest; Reticuloendothelial System, Blood; STRNTY; Scheme; Spillage; Sternotomy; Stress; Structure; Surgical; Surgical Interventions; Surgical Procedure; Surgical Procedures, Heart; System; System, LOINC Axis 4; Systole; Technology; Testing; Time; Ventricular; base; cardiac failure; cardiac muscle; commercialization; design; designing; experience; fluid; healing; heart muscle; heart surgery; hemodynamics; in vivo; in vivo Model; innovate; innovation; innovative; liquid; phase 1 study; phase 1 trial; phase I trial; pressure; programs; protocol, phase I; prototype; public health relevance; restoration; success; surgery; trend; ventricular assist device

The objective of this proposal is to develop a less invasive long-term copulsation device to treat patients in late Class III and early Class IV stages of heart failure (HF). Chronic congestive heart failure is the largest unsolved problem in cardiac care today. There are over 5.5 million people in the United States with this diagnosis and the number of patients is expected to double over the course of this decade. ABIOMED's key innovation will be an apically placed implantable partial left ventricular assist device (LVAD) system designed for copulsation, called the Apical Copulsation Device (ACD). Synchronizing assist with the heart will reduce the work required by the heart during systole and unload the left ventricle during diastole. Phase I proved the feasibility of the ACD both in bench testing using a specially designed mock loop and in three in vivo animal studies. The system control is based on the left ventricular pressure and it successfully and consistently ejected 30 ml of blood during systole after the native ventricle opened the aortic valve and completed this ejection before the valve closed. No dilatation was observed and the ACD reduced the mechanical external work required by the ventricle up to 45% with no significant increase in end-systolic pressure compared to baseline. This device can be implanted through a thoracotomy and without cardiopulmonary support, reducing the risks associated with more invasive techniques. Phase II of the program will focus on developing a durable, integrated system for extended use and characterizing its effects on the heart. There is currently no published chronic in vivo data for copulsation therapy and studies will be conducted to assess the system's hemocompatibility and how the body reacts to this type of support over time. , ,

Public Health Relevance:
Chronic heart failure (CHF) affects over 5 million Americans, with 550,000 new cases diagnosed annually. The associated mortality rates are high with CHF patients under age 65, 80% of men and 70% of women die within 8 yrs. The 1-yr mortality rate is 20%, and that figure jumps to 60% for patients with end-stage (decompensated or New York Heart Association Class IV) heart failure. There are few treatment options for end-stage CHF and medical management is the first line of treatment with limited results. Heart transplantation can provide significant individual benefit, but its impact is limited by the number of donor organs available;worldwide, less than 2900 heart transplants occurred in 2005. Over the past 15 years, mechanical circulatory support has become an established means of treating end- stage CHF. A ventricular assist device (VAD) is a blood pump that is designed to assist or replace the function of either the left or right ventricle. The device is most commonly deployed on the left side (i.e. as an LVAD), where blood is withdrawn from either the left atrium or the apex of the left ventricle. The blood then passes through the pump and is returned to the ascending aorta. The Apical Copulsation Device (ACD) proposed here affords a very effective ventricular decompression and unloading without requiring cardiopulmonary bypass or a sternotomy. The role of VADs has evolved since their clinical introduction. For end-stage CHF patients, the Thoratec HeartMate LVAD that originally received approval for bridge-to-transplant (BTT) use is now approved for alternative-to-transplant (destination therapy or DT). The results from the REMATCH study showed that for patients who are not candidates for cardiac transplantation, mechanical support increased not only the survival rate, but also scores on physical and emotional tests at one year compared to patients treated with medication. While extending the life of these patients is important, the quality of this life is paramount. Earlier treatment of HF using the ACD approach provides the opportunity to treat many more patients and may also be more effective in preserving end organ function and restoring quality of life. With over 100,000 patients in the United States receiving biventricular pacemakers each year, it is anticipated that up to 50,000 patients may be candidates for chronic copulsation therapy. The market for copulsation technologies is a sizable portion of the moderate to severe HF patient population (represented by approximately 250,000 to 300,000 annual cases in the U.S. alone) and, hypothetically, may have a very significant total market potential (estimated at $0.8 to $1.0 billion).

Thesaurus Terms:
Abdomen;Abdominal;Acute;Adverse Experience;Adverse Event;Affect;Age;Algorithms;American;Anastomosis;Anastomosis - Action;Animals;Aorta, Ascending;Aortic Valve;Aortic Valve Structure;Apical;Ascending Aorta Structure;Atrium, Left;Blood;Cadaver;Cannulas;Cardiac;Cardiac Failure Congestive;Cardiopulmonary;Cardiopulmonary Bypass;Caring;Chronic;Clinical;Computer Analysis;Congestive Heart Failure;Data;Destinations;Development;Devices;Diagnosis;Diaphragm;Diaphragm (Anatomy);Diastole;Dilatation;Dilatation - Action;Drugs;Early Treatment;Echocardiogram;Echocardiography;Emotional;Exercise;Exercise, Physical;Extracorporeal Circulation;Flow, Pulsating;Grafting, Heart;Heart;Heart Decompensation;Heart Failure, Congestive;Heart Transplantation;Heart Failure;Heart-Lung Bypass;Hemolysis;Implant;Individual;Intraventricular;Intraventricular Pressure;Lateral;Left;Left Atrium Of Heart;Left Ventricles;Left Atrial Structure;Left Ventricular Structure;Libraries;Life;Mri Scans;Marketing;Mechanics;Medical;Medication;Membrane;Methods And Techniques;Methods, Other;Monitor;Mortality;Mortality Vital Statistics;New York;Operation;Operative Procedures;Operative Surgical Procedures;Optics;Organ;Organ Donor;Pace Stimulators;Pacemakers;Patients;Performance;Perfusion, Pulsatile;Pharmaceutic Preparations;Pharmaceutical Preparations;Phase;Physiologic Intraventricular Pressure;Pressure;Pressure- Physical Agent;Procedures;Programs (Pt);Programs [publication Type];Publishing;Pulsatile Flow;Pump;Qol;Quality Of Life;Recovery;Respiratory Diaphragm;Reticuloendothelial System, Blood;Right Ventricular Structure;Risk;Role;Strnty;Scanning;Side;Staging;Sternotomy;Stimulators, Electrical, Pace;Surgical;Surgical Interventions;Surgical Procedure;Survival Rate;System;System, Loinc Axis 4;Systems Integration;Systole;Systolic Pressure;Trotmy;Techniques;Technology;Testing;Thoracotomy;Time;Transplantation;Transplantation, Cardiac;Transthoracic Echocardiography;United States;Ventricles, Right;Ventricular;Ventricular Pressure;Woman;Work;Aortic Valve;Ascending Aorta;Base;Biomedical Implant;Blood Pump;Cardiac Failure;Cardiac Graft;Commercialization;Computational Analysis;Design;Designing;Drug/Agent;Functional Restoration;Heart Bypass;Heart Sonography;Heart Transplant;Implant Device;Implantable Device;Improved;In Vivo;Incision Of Chest Wall;Incision Of Thorax;Indwelling Device;Innovate;Innovation;Innovative;Light (Weight);Membrane Structure;Men;Men's;Novel;Operation;Patient Population;Pressure;Programs;Prototype;Public Health Relevance;Restore Function;Restore Functionality;Restore Lost Function;Sensor;Social Role;Sound Measurement;Surgery;Transplant;Ventricular Assist Device;Verification And Validation