A technology which has been likened to pacing of the heart received a boost with the report of positive clinical trial data at the 10th annual scientific meeting of the Heart Failure Society of Americas (HFSA; St. Paul, Minnesota) in Seattle in late August. The Optimizer incorporates a therapy called cardiac contractility modulation (CCM), and data on the device was presented at a late-breaking clinical trials session by Martin Borggrefe, MD, director of Cardiology, Angiology and Pneumology of the Medical Clinic I, University Hospital Mannheim (Mannheim, Germany) and lead investigator of the study. The data from the Fix Congestive Heart Failure 4 (FIX-CHF-4) indicated both clinical improvement and positives in quality-of-life measures.
The device, or rather devices — since the study looked at two generations of the system — is made by Impulse Dynamics USA (Orangeburg, New York), a subsidiary of Impulse Dynamics NV (the Netherlands Antilles). The company said that the trial is the largest randomized study to date to evaluate the Optimizer.
The Optimizer system consists of a pacemaker-like device and conventional pacing leads which deliver the therapy to the cardiac tissue. The device is implanted much like a pacemaker, but as compared to conventional pacing, the device uses the company’s CCM therapy in which electrical impulses are delivered to the heart after it already has initiated its contraction. And unlike conventional pacing signals, CCM is designed to increase the force of the heart’s pumping action rather than initiating a new contraction.
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.
Daniel Burkhoff, MD, PhD, chief medical officer at Impulse, said that CCM “does not pace, it does not initiate a contraction, but it tries to help the heart beat stronger.” Burkhoff also noted a key difference between the trials for the Optimizer and those for cardiac resynchronization therapy systems which also are designed to treat heart failure patients. “CRT is for heart failure patients who have left ventricular dyssynchrony. We studied patients who have heart failure but do not have mechanical dyssynchrony,” he told Cardiovascular Device Update.
“This study was designed to see the effects in patients without dyssynchrony, so with normal Q [wave] restoration, and see in a prospective randomized trial whether we see any benefits,” Borggrefe said. He also noted another key difference between CRT and the Optimizer. The CRT patient population, he said, accounts for only about 10% to 15% of the total heart failure population, whereas the patient population represented in the FIX-CHF-4 study represents nearly 70% of the total heart failure patient pool.
Impulse Dynamics says that rather than being a “no option” therapy, the Optimizer is most likely to be used for many patients who do not yet require resynchronization but provides them with very similar benefits — that is, not just inhibiting increased deterioration of the heart’s ability to pump but potentially improving it.
In the study, 126 patients, average age of 60 and a mean ejection fraction of 25%, received an Optimizer implant and were randomized into one of two groups. For the first 12-week phase of the study, the Optimizer was activated in the first group of 62 patients and remained off in the second group of 64 patients. During the second 12-week phase, the groups crossed-over. The study was double blinded; neither doctors nor patients knew whether the Optimizer was turned on.
During Phase I of the study, peak oxygen consumption increased similarly in both groups by ~0.8 ml/kg/min, independent of whether the device was turned on or off. In the second phase of the study, subjects who crossed over from non-active treatment to active treatment exhibited a further increase in peak oxygen consumption, whereas peak oxygen consumption decreased back to baseline in subjects who crossed from active treatment to non-active.
At the end of the second phase, a 1.25 ml/kg/min difference in peak oxygen consumption between the groups was found.
“The similar peak oxygen consumption rates seen in the two groups at the end of the first 12-week period indicates a relatively prominent placebo effect,” Borgreffe told CDU. “However, the difference at the end of the full 24-week period showed that active treatment significantly improved maximal exercise tolerance.”
Importantly, Borgreffe pointed out that the two generations of the device used in the trial — the Optimizer II and Optimizer III — had no impact on the study results since the primary difference between the two devices was the battery life for the product. “Because the device uses more energy than a conventional pacemaker, the earlier generation of the device only had longevity of about six to eight months.” With the introduction of the Optimizer III, he said the company engineered a rechargeable battery to solve the longevity problem.
“Notwithstanding the medical advances we have seen with beta-blockers, ACE inhibitors, cardiac resynchronization therapy and implantable cardiac defibrillators, these methods still fall short in meeting the needs of all heart failure patients as many continue to suffer from exercise intolerance, frequent hospitalizations and high mortality,” said Borggrefe. “Today’s findings are an important step in the evaluation of this new application in the hopes of becoming an easily deployable treatment made available to patients with otherwise untreatable symptoms.”
The Optimizer is CE-marked and currently under clinical investigation at U.S. research and academic facilities.
Elsewhere in the product pipeline:
• Angiotech Pharmaceuticals (Vancouver, British Columbia) reported positive preclinical data related to its Vascular Wrap paclitaxel-eluting mesh and Lifespan graft technology at the Western Vascular Society 2006 annual meeting at La Jolla, California. “We are excited by the potential of the Vascular Wrap paclitaxel-eluting mesh product in a variety of indications, including AV access for hemodialysis patients,” said Dr. William Hunter, Angiotech president/CEO. Although synthetic grafts are currently used in about 40% of hemodialysis patients who require permanent vascular access, primary patency rates remain poor. Most graft failures are caused by scar tissue growth inside the graft (neointimal hyperplasia) at the location where the graft is connected to the vein (the graft-vein anastomosis). Currently, about 50% of grafts fail within one year and about 75% within two years as a result of scar formation, according to Angiotech. This preclinical study was designed to evaluate the effect of the Vascular Wrap bioabsorbable mesh containing paclitaxel on inhibiting neointimal hyperplasia in an animal model of dialysis access failure, said Angiotech. In the study, neointimal hyperplasia was reduced by a minimum of 87.6% in animals that received a paclitaxel-eluting mesh compared with animals that received no mesh.
• ATS Medical (Minneapolis) reported clinical results for the ATS Open Pivot Heart Valve in “A Single Institution Outcome Analysis of St. Jude Medical and ATS Open Pivot Bileaflet Heart Valve Prosthesis.” The study compares the mid-term outcomes of 1,161 patients receiving either the ATS Open Pivot Heart Valve or the St. Jude Medical (St. Paul, Minnesota) mechanical heart valve. The results were to be presented at the 16th World Congress of the World Society of Cardio-Thoracic Surgeons in Ottawa, Ontario.
• Biosense Webster (Diamond Bar, California) said the FDA has granted an expanded indication to the NaviStar ThermoCool Catheter, an automated ablation system supporting an open-loop irrigated catheter. The device is now available for the treatment of adults with specific rapid heartbeats, for whom other treatments have failed. The ThermoCool Catheter is the first FDA-approved catheter to treat both mappable and unmappable ventricular tachycardias. Biosense, a Johnson & Johnson company, makes electrophysiology diagnostic, therapeutic, and mapping tools.
• BioSphere Medical (Rockland, Massachusetts) sponsored a symposium about its HepaSphere Microspheres product used to treat primary and metastatic liver cancer on Sept. 10 at the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) annual meeting in Rome. BioSphere has filed a 510(k) premarket notification with the FDA seeking marketing clearance for QuadraSphere Microspheres for the treatment of hypervascularized tumors and peripheral arteriovenous malformations. QuadraSphere is technically identical to HepaSphere, but the 510(k) application for QuadraSphere includes specific indications for use in treating primary and metastatic liver cancer. Biosphere bioengineers microspheres to treat uterine fibroids, hypervascularized tumors and vascular malformations.
• CardiacAssist (Pittsburgh) reported that it has placed the TandemHeart PTVA system at three new medical centers: Geisinger Health System (Danville, Pennsylvania), Hoag Memorial Hospital Presbyterian (Newport Beach, California), and Westchester Medical Center (Valhalla, New York). According to CardiacAssist, the TandemHeart provides circulatory support through a cardiac catheterization procedure in as little as 30 minutes and can provide up to five liters per minute (lpm) of blood flow. CardiacAssist makes products to provide extracorporeal circulatory support for cardiologists and cardiac surgeons.
• CardioDynamics (San Diego) reported the draft coverage decision for hypertension from the Centers for Medicare & Medicaid Services (CMS). The draft decision proposes continuing the current policy for coverage of impedance cardiography (ICG) for resistant hypertension, defined as patients whose blood pressure is not controlled on three or more medications. Reimbursement coverage is still provided for Medicare patients with shortness of breath and heart failure. The draft decision for hypertension coverage was subject to an immediate 30-day public comment period to conclude on Sept. 23. CMS anticipates a final National Coverage Determination by Nov. 21. Cardiodynamics makes noninvasive ICG products and medical device electrodes.
• Cordis (Miami Lakes, Florida) reported the availability of its Steer-It Deflecting Tip Guidewire for commercial use in the U.S., Canada and Europe. The Steer-It Deflecting Tip Guidewire is used in positioning catheters and other interventional devices, such as drug-eluting stents, in a patient’s coronary. It can also be used in peripheral arteries. The tip can be manipulated to bend in two directions, and is specially designed to help physicians treat hard-to-reach blockages, including those in tortuous vessels, previously deployed stents or side branches of an artery. Cordis, a Johnson & Johnson company, manufactures interventional vascular technology.
• Corgenix Medical (Denver) and strategic partner Creative Clinical Concepts (CCC) have received U.S. patent No. 7,081,347, titled “Unique Methods for ‘Assessing Aspirin Resistance’ and Risk of Cardiovascular Disease in Patients Taking Aspirin.” The patent approval covers the ability of the AspirinWorks Test Kit to assess a patient’s resistance to the anti-clotting effects of aspirin. Corgenix manufactures specialized diagnostic kits for immunology disorders, vascular diseases, and bone and joint disorders.
• Impliant (Milford, Connecticut) reported that it has received FDA approval to begin a clinical trial for its TOPS system, a total posterior arthroplasty system designed to treat spinal stenosis with or without facet arthrosis and spondylolisthesis. “Our surgeon investigators view the TOPS System as a viable alternative to spine fusion to treat patients with late stage degenerative pathologies,” said Todd Potokar, president of Impliant. Impliant develops spine arthroplasty solutions for motion preservation.
• Medtronic (Minneapolis) said a study published recently in the American Heart Association journal Circulation provided evidence of the safety and effectiveness of the Medtronic Endeavor drug-eluting coronary stent system for patients with coronary artery disease, with a clinically significant treatment effect that is being sustained over time. The trial enrolled 1,197 patients at 72 facilities in 17 countries and was the first and largest drug-eluting stent trial outside the U.S. comparing a drug eluting stent to a bare-metal stent. “These excellent clinical outcomes have been maintained at nine months, 12 months and 24 months. Compared to bare-metal stents, Endeavor is safe and effective in reducing the rates of clinical and angiographic restenosis, and is a highly deliverable stent that has significant anti-restenosis properties and a favorable safety record with dual anti-platelet therapy,” said William Wijns, MD, the co-principal investigator of the trial.
• Royal Philips Electronics (Andover, Massachusetts) reported that its line of HeartStart Defibrillators is compliant with American Heart Association (AHA), European Resuscitation Council (ERC), and International Liaison Committee on Resuscitation (ILCOR) 2005 Guidelines for Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care (ECC). All HeartStart Defibrillators now shipping, including the Home, OnSite (HS1), FRx, FR2+, XL and MRx, support the new protocol of single-shock defibrillation, followed by immediate CPR, which is recommended in the updated guidelines. Royal Philips is a worldwide leader in defibrillation technology and electronics.
• ZOLL Medical (Chelmsford, Massachusetts) reported that it has been granted FDA 510(k) marketing clearance for a new defibrillator designed for hospitals. ZOLL said it will launch the product in 2007. ZOLL makes products to resuscitate sudden cardiac arrest or trauma victims including pacing, defibrillation, circulation, ventilation, and fluid resuscitation.