The Optimizer III, a pacemaker-like device being developed for a broad niche targeting restoration of heart function – but quite different from a pacemaker – received its first implantation in the launch of a Phase II U.S. study earlier this month.
The patient, a 70-year-old retired construction worker, was implanted at St. Joseph’s Hospital (Atlanta), becoming the first enrollee in the Fix Heart Failure 5 (FIX-HF-5) study sponsored by Impulse Dynamics USA (Orangeburg, New York), a subsidiary of Impulse Dynamics NV of the Netherlands Antilles. The company’s Israeli unit in Tirat Hacarmal is the device developer and manufacturer.
The Optimizer III System, as its name indicates, is an advanced generation of this system, which is designed to deliver to the heart a specialized form of electrical impulses. The study will enroll about 400 New York Heart Association Class III or Class IV heart failures patients at up to 50 sites. The company already has won CE-marking for the Optimizer II in Europe.
The Optimizer system uses a strategy that Impulse Dynamics has titled cardiac contractility modulation (CCM). The company describes CCM therapy as the delivery of “non-excitatory impulses to the heart during a period of time called the absolute refractory period [ARP].” In contrast to the electrical impulses delivered by a pacemaker, CCM impulses do not modify the beating activity of the heart but rather are intended to work on heart cell function.
William Abraham, chief of the division of cardiovascular medicine at Ohio State University (Columbus) and co-principal investigator of the study, says that the Optimizer’s primary value is in improving the “contractility” of the heart but without adding to its overall workload.
He acknowledges that the device’s mechanism of action is not fully understood. But the apparent mechanism, he told Medical Device Daily, is “to work in part by modulating the handling of calcium within the heart cells and, as we know, the contractility of the heart – the need for the heart to squeeze – is mediated in part by calcium.”
Abraham adds: “The grand news here is that what you see at the gross cardiac level is an increase in the pumping ability of the heart in association with a decrease in workload. Myocardial oxygen consumption actually goes down while the contractility goes up. It improves the efficiency of the heart and that’s obviously a good thing.”
By contrast, he says, other systems that work to improve contractility may also increase workload and thus have what he terms “mixed results.”
“Mechanistically,” Abraham says, “the Optimizer does all the right things – that’s why we have so much optimism about this particular therapy.”
Abraham has been involved in a variety of heart therapy research for 15 years, including drug therapy and some of the earliest work in the area of heart resynchronization, and he remains involved in these types of studies.
Guidant (Indianapolis) four years ago acquired an option to buy from Impulse Dynamics certain aspects of the CCM technology but then backed away from exercising that option, saying instead that it would focus on its resynchronization technologies (MDD, Jan. 30, 2001).
Abraham noted that the Optimizer may actually target a larger market than does resynchronization. Rather than being a type of “no option” therapy, it is most likely to be used for many patients who do not yet require resynchronization but providing them with very similar benefits – that is, not just inhibiting increased deterioration of the heart’s ability to pump but potentially improving it.
Abraham says that he had been aware of the work of Impulse Dynamics and that “they approached me for some guidance on issues regarding design and implementation of a pivotal trial.”
Besides looking at safety and effectiveness, FIX-HF-5 will look at a variety of secondary endpoints, most importantly its ability to “remodel” the heart, he says, “to see if we’re actually making the heart smaller – and stronger, over time.”
The study researchers, he says, expect fairly rapid enrollment in the new Optimizer study, because of the ability to identify the target patient pool via EKG studies.
He notes also that implantation of the Optimizer involves no additional training for cardiac surgeons, since it is implanted very much like a pacemaker and with pacemaker-like leads. The leads sense the appropriate timing and sequencing opportunities to deliver the CCM impulses, with the specialized circuitry and algorithms then pre-programmed for patient needs. The device then employs radio frequency telemetry to create graphical displays of its activity to further customize programming.
The current trial is follow-on to a Phase I study that completed enrollment in December 2004 and included 50 patients implanted with an Optimizer system.
A variety of data concerning the Optimizer will be presented in oral and poster presentations at the annual meeting of the Heart Rhythm Society (Washington) in New Orleans early next month.
Nirav Raval, principal investigator of the study at St. Joseph’s, said, “We are excited about our participation in this study because if the results support safety and effectiveness, the Optimizer’s Cardiac Contractility Modulation technology could be a significant advance in heart failure treatment and may help a large number of patients.”
Virginia Commonwealth University Medical Center (Richmond, Virginia) also said this month that it has begun the process of enrolling patients in the Phase II study of the Optimizer.
Symptoms of heart failure result when the heart is unable to pump enough blood to meet the energy needs of the body. A failing heart most often results from damage to the heart muscle due to injuries such as heart attack, untreated coronary artery disease or persistent high blood pressure.
Research and development at Impulse Dynamics, the company says, are focused on refining the principle and practice of modifying tissue properties and function through the predictable and reproducible delivery of electrical signals.