Entrepreneurs developing active implantable medical devices
Pacesetter Human Tissue Stimulator (HTS) (c) David Prutchi, Ph.D., 2024
I recently acquired this device on eBay® (from a very kind seller, I may add). Although labeled as a “Rechargeable Pacemaker,” and looks just like the one at the Udvar-Hazy about which I had posted a few years ago, it is in fact a neurostimulator.
The Human Tissue Stimulator or “HTS” was developed subsequently to the rechargeable pacemaker, prompted by the clinical need for a rechargeable implantable neurostimulator.
First-generation RF-powered BION (RFB1) microstimulator. Image Credit: Alfred Mann Institute for Biomedical Engineering
In 1991, Dr. Gerald Loeb, at the time a Professor of Physiology and Biomedical Engineering at Queen’s University (Kingston, Canada), first proposed a miniature, injectable, RF-powered device for the stimulation of tissue or motor neurons. The BION® device was developed based on this concept as a joint project between Queens University (Kingston, ON, Canada), IIT (Chicago, IL), and the Alfred E. Mann Foundation (Valencia, CA) with funding from the NIH Neural Prosthesis Program. The RF BION 1 (RFB1) was then manufactured by the Alfred Mann Institute for Biomedical Engineering at USC.
Image Credit: BrainsGate
BrainsGate is an Israeli company that was established in 2000. It developed an implantable device for the stimulation of the Spheno-Palatine Ganglion (SPG) to modulate the brain-blood barrier and increase cerebral blood flow.
On December 10, 2021, BrainsGate’s clinical study was discussed by an FDA panel, which although agreed on the safety of the system, did not find the device sufficiently effective as a treatment for stroke, whereby its benefits would outweigh the risks.
The voting was:
FDA does not have to follow the recommendations of its panels, but it mostly does (approximately 80% of the time), and such low vote of confidence does not bode well for BrainsGate’s SPG stimulation as a treatment for ischemic stroke.
Image Credit: BrainsGate
Intec AID-B. (c) 2021 David Prutchi, PhD.
Conceived by physicians Michel Mirowski and Morton Mower, and supported by Dr. Stephen Heilman, the first automatic implantable defibrillator was developed and manufactured under the name of “AID” by Medrad/Intec Systems in Pittsburgh, PA.
It was encased in titanium and hermetically sealed with a laser beam weld. It had a volume of 145 ml and weighed 250 gm. The device was powered by lithium batteries which had a projected monitoring life of 3 years or a discharge capability of 100 shocks.
The ICD was designed to detect ventricular fibrillation and sinusoidal ventricular tachycardia, and it attempted to using a truncated exponential 25 Joules pulse. The device could recycle three times during a single episode with the third and fourth pulses delivered at 30 Joules.
The device was meant to be connected to electrodes made from titanium and coated with silicone rubber. One defibrillating electrode was located intravascularly in the superior vena cava (SVC) at the right atrial junction. The second electrode had the configuration of a rectangular patch or a cup and was positioned over the cardiac apex.
First implants of the device were conducted at the Johns Hopkins Hospital in Baltimore in 1980. These devices were not programmable and manufactured on an individual basis. The AID was then improved with rate-counting circuitry and could synchronize shocks with the R-wave. Efforts were also made to reduce the recycling time after a failed shock. The new device was called the AID-B (shown in the picture), but was still manufactured according to individual specifications.
Circuitry of the AID-B implantable defibrillator. From: PJ Troup, “Implantable Cardioverters and Defibrillators”, Current Problems in Cardiology, Volume 14, Issue 12, December 1989.
Impulse Dynamics – the company for which I work – announced during HRS that a first patient received the Optimizer® Smart System for delivering CCM™ therapy since the device was approved by the U.S. Food and Drug Administration. The implant was performed on May 6, 2019 at The Ohio State University Wexner Medical Center.
The start of commercial implants in the U.S. is a major milestone for the Company. It makes me very proud that the technology on which I have worked for over 21 years is now available to make a dramatic change to the lives of heart failure patients across the U.S.
I have led the development of devices to deliver CCM™ therapy from the very beginning, so it is with great pleasure and pride that I share with you the exciting news that Impulse Dynamics just received approval from the United States Food and Drug Administration (FDA) for our Optimizer® Smart System for heart failure patients! An official FDA announcement was made through the publication of a press release that you can find here: https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm634103.htm.
Impulse Dynamics’ press release is as follows:
Impulse Dynamics receives FDA approval for breakthrough Optimizer® Smart System delivering CCM™ therapy for treatment of heart failure
Orangeburg, New York, March 21, 2019 – Impulse Dynamics, developer of the implantable Optimizer® Smart System for delivering CCM™ therapy, announced today that it has received approval from the United States Food and Drug Administration for its first-in-class Optimizer Smart System.
Designed to address a significant unmet medical need in heart failure, the Optimizer Smart System received Breakthrough Device designation from the FDA in 2015. It was the first breakthrough device to go before the Circulatory System Devices Panel of the FDA’s Medical Devices Advisory Committee, on Dec. 4, 2018, receiving a 12-0 vote on the benefit-to-risk ratio of the device.
“With the FDA’s approval of the Optimizer System for the delivery of CCM, we finally have available in the US an effective device-based therapy for advanced heart failure patients with mildly to moderately reduced left ventricular ejection fractions who are not eligible for CRT,” said Professor William T. Abraham, MD, Professor of Medicine, Physiology, and Cell Biology, and College of Medicine Distinguished Professor at the Ohio State University Wexner Medical Center. “The Optimizer System, along with guideline-directed medical therapies, can improve the lives of many heart failure patients in the US who previously did not have access to this therapy. As such, it represents a real game-changer for these patients.”
The Optimizer Smart System is the first and only CCM device approved by the FDA to improve 6-minute hall walk distance, quality of life and functional status of NYHA Class III heart failure patients who remain symptomatic despite guideline directed medical therapy, who are in normal sinus rhythm, are not indicated for CRT, and have an LVEF ranging from 25% to 45%. Only 30 percent of moderate to severe chronic heart failure patients are candidates for CRT, which historically has left 70 percent of patients with few options to help them manage their disease.
“FDA approval is the culmination of many years of clinical development for this disruptive technology, addressing a significant unmet need in today’s heart failure treatment paradigm,” commented Dr. Daniel Burkhoff, Impulse Dynamics’ Medical Advisor. “We continue to develop the technology with ongoing clinical trials designed to evaluate CCM therapy in additional heart failure populations.”
CCM is a unique electrical pulse delivered during the absolute refractory period, which is just after the heart contracts. In contrast to a pacemaker or defibrillator, CCM works by modulating the strength of the heart muscle contraction rather than the rhythm.
Dr. Simos Kedikoglou, Impulse Dynamics’ CEO, announced that the Company will launch the device in the US later this year. “We are extremely excited that the Optimizer Smart System with CCM therapy is now available in the United States,” he said. “We look forward to growing our commercial presence in the US and globally.”
About the Optimizer and CCM Therapy
CCM is the brand name for Cardiac Contractility Modulation, the non-excitatory electrical pulses delivered by the implantable Optimizer device during the absolute refractory period of the heart cycle to improve systolic contraction of the heart. The Optimizer System has been implanted in over 3,500 patients and is currently available in Europe, China, Brazil, India, and more than 40 other countries around the world. Impulse Dynamics has completed numerous clinical studies, including several randomized controlled trials. The results have been published in over 80 papers in leading medical journals.About Impulse Dynamics
Impulse Dynamics is focused on the development of electrical therapies for the treatment of chronic heart failure. As a global leader in cardiac medical innovation, Impulse Dynamics has operations in the United States, Europe, and Asia. For more information please visit www.impulse-dynamics.com.Impulse Dynamics (USA), Inc.
30 Ramland Road South, Suite 204
Orangeburg, NY 10962
Yesterday I visited the Udvar-Hazy Center of the Smithsonian Air & Space Museum in Chantilly, VA. There I found this demo rechargeable pacemaker being displayed as a spinoff of NASA’s technology with the following explanation:
I can’t remember exactly where I found the picture of a Pacesetter model BD102 VVI, but the story behind it is documented by Kirk Jeffrey in “Machines in our Hearts”:
“In 1968, Robert Fischell, of the Applied Physics LOaboratory at Johns Hopkins University, and cardiologist Kenneth B. Lewis had begun a collaboration that led in 1973 to a new kind of Ni-Cad battery able to function more effectively at body temperature and hermetically sealable. Alfred E. Mann, a California entrepreneur with background in the aerospace industry, had provided some financial support to the Hopkins group. Eventually Mann founded a small company to develop a pacemaker for the rechargeable battery; this was the origin of Pacesetter Systems. The rechargeable pacemaker reached the market in the summer of 1973, just as CPI introduced its lithium pacer.”
Image Credit: NeuroPace
NeuroPace is a privately-held company in Mountain View, CA. Their RNS® implantable stimulator, along with depth leads and cortical strip leads are designed for the treatment of medically refractory partial epilepsy.
On November 14, 2013, NeuroPace has now received FDA pre-market approval for the NeuroPace RNS System as a treatment for adults with partial onset seizures that have not been controlled with two or more antiepileptic drugs.
According to the press release:
The RNS System has been evaluated in three clinical trials, including a prospective, randomized, double-blinded, sham stimulation controlled pivotal study. The pivotal study primary effectiveness endpoint was met by demonstrating a 37.9 percent reduction in seizure frequency in patients treated with responsive stimulation compared to a 17.3 percent reduction in patients who were implanted with the device but were not receiving responsive stimulation during a three month blinded period. The difference is statistically significant (p=0.012). For those subjects who reached two years post-implant, 55% of the subjects experienced a 50% or greater reduction in seizures.
Unlike Cyberonics’ VNS IPGs, the RNS neurostimulator is designed to detect abnormal electrical activity in the brain and respond by delivering electrical stimulation to normalize brain activity before the patient experiences seizure symptoms. The neurostimulator is implanted in the cranium and connected to one or two leads that are implanted near the patient’s seizure focus.
From Patent Application Publication: US 2011/0137370 A1
Sorin recently announced a $5 million investment in Israeli startup Enopace Biomedical, which is developing an endovascular neurostimulation system for heart failure. Back in October 2011 Sorin invested $7 million to finance the initial clinical studies of Enopace’s technology as well as ongoing product development.
Very scant details are available besides that it is developing a neuromodulation system to treat patients with congestive heart failure. According to the company, its technology consists of a minimally invasive, implantable neurostimulation device that increases cardiac efficiency by reducing left ventricular workload.
From Enopace’s patent applications, it seems that Enopace’s device consists of a stimulation unit that is placed within the aorta close to the heart, and which is driven wirelessly from a coil that is placed within a vein closeby to the artery. The transmitting coil is in turn driven from an implanted control unit that is implanted subcutaneously.
Israeli business news website “Globes” interviewed Enopace’s CEO Amir Dagan, and reported in February 2013:
Image Credit: NeuroPace
NeuroPace is a privately-held company in Mountain View, CA. Their RNS® implantable stimulator, along with depth leads and cortical strip leads are designed for the treatment of medically refractory partial epilepsy.
Unlike Cyberonics’ VNS IPGs, the RNS neurostimulator is designed to detect abnormal electrical activity in the brain and respond by delivering electrical stimulation to normalize brain activity before the patient experiences seizure symptoms. The neurostimulator is implanted in the cranium and connected to one or two leads that are implanted near the patient’s seizure focus.
NeuroPace recently disclosed that it has raised about $18 million of a planned $50 million in new funding. NeuroPace has raised about $180 million since it was founded in 1997.
Impulse Dynamics (yes, the company for which I work) launched its new, CE-marked OPTIMIZER™ IVs implantable device for the treatment of heart failure at the 79th Annual Meeting of the German Cardiac Society (Mannheim, Germany, 3–6 April 2013).
The OPTIMIZER™ IVs Implantable Pulse Generator (IPG) is a programmable telemetric device intended to treat moderate to severe heart failure resulting from left ventricular dysfunction by monitoring intrinsic cardiac electrical activity and delivering Cardiac Contractility Modulation (CCM) signals during the ventricular absolute refractory period. These electrical signals are intended to influence myocardial properties in patients, thereby reducing their symptoms and improving quality of life and exercise tolerance.
The OPTIMIZER™ IVs IPG was designed to deliver CCM signals during the ventricular absolute refractory period in synchrony with locally-sensed electrical activity. The microprocessor controlled implantable device comprises intracardiac electrogram sensing circuits, control logic, communications circuitry, and circuitry to generate the CCM signals. Electrogram signals are detected from and CCM signals are delivered to the heart using standard chronically-implantable bipolar pacing leads. The implant procedure is similar to implantation procedures for other cardiac rhythm management devices.
On February 4, 2013, after more than 20 years of research and development, Second Sight Medical Products, Inc., announced that its Argus® II Retinal Prosthesis System (“Argus II”) has received U.S. market approval from the Food and Drug Administration (FDA) to treat individuals with late stage retinitis pigmentosa (RP). This announcement follows receipt of the European approval in 2011, and a unanimous recommendation by the FDA’s Ophthalmic Devices Advisory Panel in September 2012 that this revolutionary product be made available to treat this patient population in the U.S.
Spinal Modulation was founded by Mir Imran in Menlo Park, CA in 2004. The company has developed an implantable neurostimulator to deliver signals to the primary sensory neurons located within the dorsal root ganglion (DRG). The idea is that unlike dorsal column spinal cord stimulation, the Spinal Modulation system breaks the pain signal’s path before it enters the spinal cord. Continue reading
BioControl Medical, Ltd. was founded in 1999 by Yossi Gross, and is based in Yehud, Israel. BioControl’s first devices were developed to treat incontinence due to overactive bladder, stress, and interstitial cystitis. In 2006 American Medical Sytems acquired an exclusive license for the use of the technology in urology, gynaecology and other pelvic health applications.
The BioControl MiniatURO was an implantable muscle and nerve stimulator designed for subcutaneous implantation on an outpatient basis. Its purpose was to alleviate some types of urinary incontinence.
For patients suffering from stress incontinence, whenever the device detected an increase in abdominal pressure through its pressure-sensing catheter, it applied mild electrical pulses to the pelvic floor muscles. The intention was to activate the muscles and prevent inadvertent urine loss. In the urge incontinence mode of operation, the unit applied mild electrical pulses to the pelvic diaphragm nerve, using the sphincter detrusor muscle reflex to inhibit bladder contractions. For those with both types of incontinence, the two modes of operation were combined. In operation, the unit was intended to mimic natural physiology, activating the muscle upon demand, and strengthening the pelvic floor muscle. Continue reading
BioControl Medical, Ltd. was founded in 1999 by Yossi Gross, and is based in Yehud, Israel. BioControl’s first devices were developed to treat incontinence due to overactive bladder, stress, and interstitial cystitis. In 2006 American Medical Sytems acquired an exclusive license for the use of the technology in urology, gynecology and other pelvic health applications. Continue reading