A trilogy of cardiovascular products from three separate companies received good news on the regulatory front the week before Christmas.
Medtronic (Minneapolis, Minnesota) received FDA approval of the Medtronic Marquis VR ICD (implantable cardioverter defibrillator) and has begun distribution of the product to U.S. physicians. The Marquis VR ICD features more than 20 new or updated technological advances, including the company's Wavelet algorithm that discriminates between types of arrhythmias to minimize the chance of unnecessary therapies. Other product features provide heart disease progression data for physicians and simplify post-implant office visits for patients. The Wavelet algorithm is designed to help reduce inappropriate therapies by improving the classification of fast rhythms in the upper chambers of the heart. Wavelet reviews as many as 48 different aspects of the patient's arrhythmia waveforms and compares them with stored examples of patients' normal heart rhythms, which improves the detection of arrhythmia types and helps determine when treatment is warranted.
Based on the new Marquis ICD platform, the Marquis VR is the single-chamber version of the widely used dual-chamber Marquis DR ICD, which was approved by the FDA last March. In September, the American College of Cardiology (ACC; Bethesda, Maryland), American Heart Association (AHA; Dallas, Texas) and North American Society of Pacing and Electrophysiology (NASPE; Natick, Massachusetts) issued expanded guidelines for physician use of ICDs. Based on the MADIT II clinical study, the guidelines recommend that a new group of heart attack survivors those who are at risk for sudden cardiac arrest and have poor heart pumping function (ejection fraction of less than or equal to 30%) should get an ICD. Ejection fraction is a measurement of the volume of blood expelled from the lower chambers with each heartbeat.
"The new Wavelet algorithm's ability to accurately detect when a heart rhythm becomes life-threatening is a critical advancement for both patients and physicians," said Marshall Stanton, MD, Medtronic Cardiac Rhythm Management medical director and vice president, in a statement. "While the MADIT II trial was a significant addition to the mounting body of evidence that ICDs should be used to help protect those at risk for sudden cardiac arrest, a sizeable percentage of patients in the ICD trial arm received a defibrillation shock when they didn't need one. The design of our Wavelet technology helps address this concern."
"The Marquis VR's capacity to discriminate between arrhythmias that are life-threatening and those that are not provides a[n] ... advantage in reducing inappropriate therapies," said Steven Compton, MD, of the Alaska Heart Institute (Anchorage, Alaska), a Marquis VR clinical trial investigator.
The Marquis VR also is the smallest ICD device available from Medtronic, weighing 75 grams and measuring 36 cc in size. The device is fully compatible for use with the Medtronic CareLink Network, an Internet-based service that connects patients and physicians for virtual office visits.
Guidant (Indianapolis, Indiana) received CE mark approval for the Multi-Link Vision Coronary Stent System, the company's first cobalt chromium stent platform for the treatment of coronary artery disease. The company said the system's cobalt chromium alloy provides "excellent radial strength and visibility and allows the stent to have thin stent struts and superb deliverability." John Capek, PhD, president of Guidant's Vascular Intervention business, said, "The Multi-Link Vision Stent System pioneers an innovative new class of stents powered to perform with low nickel content cobalt chromium, an alloy that sets a new standard for value in stent design technology." He added that the thin-strut design "has shown excellent clinical results, with a nine-month clinically-driven target lesion revascularization rate of 6.2%."
A company spokesperson said the Vision could be characterized as a mid-sized stent system, and added that Guidant plans to use cobalt chromium stents in future stent and drug-eluting stent platforms, and will introduce a small-vessel cobalt chromium stent in Europe in 2Q03. He said the company still plans to maintain its Multi-Link family of stainless steel systems for the treatment of coronary artery disease, including the mid-sized Zeta, the Pixel for small vessels and the Ultra for larger-sized vessels. "Because it's cobalt chrome and offers this great profile, it's possible that [the Vision stent system] can be used in different patient subsets in place of a drug-eluting stent," he said, adding that the company filed a premarket approval (PMA) application in the U.S. in October and expects an FDA approval for the system "in the first half of 2003."
Due to what it said were the system's "excellent clinical results and performance characteristics," Guidant said the cobalt chromium stent will be priced at a premium to stainless steel metal stents currently on the market. "We're still positioning it as roughly half the cost of a drug-eluting stent," the spokesperson said, noting that drug-eluting stents cost between $2,500 and $3,000 apiece.
End-stage congestive heart failure (CHF) product developer MicroMed Technology (Houston, Texas), received CE mark approval to incorporate Carmeda AB's (Uplands Vasby, Sweden) BioActive Surface (CBAS) into the MicroMed DeBakey VAD. Carmeda supplies CBAS, the heparin coating which is designed to improve the hemocompatibility of medical devices. The DeBakey VAD is a miniaturized axial flow heart-assist pump, for end-stage heart failure patients that measures one by three inches and weighs less than four ounces.
The Carmeda thromboresistant surface reduces the aggregation of blood products on the device surface, thereby reducing complications occurring on the device. Proven benefits of Carmeda on device surfaces, according to the companies, include reduced platelet aggregation, lower thrombus accumulation, reduction of inflammatory response, and compatibility with surrounding tissue. Long-term bioactivity, coupled with the fact the stable heparin coating does not leave the device surface, differentiates the surface from other coatings. The FDA has approved the sale of CBAS-coated coronary stents, oxygenator circuits and other devices.
"To date, 56 patients have been implanted with the CBAS-coated DeBakey VAD and results appear promising," said Dr. Deborah Morley, vice president of clinical affairs for MicroMed. "If these positive outcomes continue as the number of patients are increased, MicroMed expects to demonstrate value for the Carmeda coating on its unique miniaturized axial flow pump." MicroMed recently received FDA approval for use of the Carmeda coating on its pumps for a bridge-to-transplant clinical trial in the U.S. The launch with this coating will begin at year-end. The DeBakey VAD has the CE mark and is in clinical trials in the U.S.
Elsewhere in the product pipeline:
Abbott Laboratories (Abbott Park, Illinois) reported the recent launch of the Perclose A-T (Auto-Tie), the latest generation in suture-mediated vessel closure systems from Abbott Vascular Devices, the company's cardiovascular device franchise. While Abbott's suture-mediated closure has been known for a secure close after cardiac catheterization procedures, many physicians had considered tying the knot the most difficult step of the procedure. By eliminating knot tying, the new Perclose A-T is designed to provide an added convenience for clinicians and helps to reduce the vessel closure procedure time, the company said.
Bristol-Myers Squibb Medical Imaging (North Billerica, Massachusetts) said a study published in the Journal of the American Medical Association reported that the addition of its Cardiolite (Kit for the Preparation of Tc99m Sestamibi for Injection) noninvasive heart imaging test called to conventional evaluation techniques can help doctors in the emergency department better distinguish between those patients who are having a heart attack and those who are not. Researchers say the results of this study could serve as the basis for a new standard of care for chest pain assessment in emergency departments nationwide. A Cardiolite imaging test, also called sestamibi imaging, allows doctors to noninvasively evaluate the heart's pumping ability and gauge the amount of blood flow to the heart muscle itself and thus can quickly assess whether or not a patient is having a heart attack. The study, the Emergency Room Assessment of Sestamibi for Evaluation of chest pain (ERASE Chest Pain Trial), is the first randomized, multicenter, controlled clinical trial designed to prospectively evaluate the impact of Cardiolite imaging on emergency department triage decisions. Researchers evaluated 2,475 patients with symptoms suggestive of heart attack or acute cardiac ischemia who had a normal or non-diagnostic ECG. Among patients who received Cardiolite, unnecessary hospitalizations were reduced by 20% among patients without acute cardiac ischemia, without reducing appropriate admissions for patients with acute ischemia.
CryoCor (San Diego, California) said that four patients with atrial flutter have been treated successfully with the CryoCor Cardiac Cryoablation System. The procedures were conducted at the Iowa Heart Center (Des Moines, Iowa) by Ben Johnson, MD, and Robert Hoyt, MD, and The Lahey Clinic (Burlington, Massachusetts) by David Martin, MD. The procedures were performed as part of a feasibility study under an investigational device exemption granted by the FDA. The four patients are the first of 30 patients for whom the company has approval to perform the procedure. The purpose of the study is to evaluate the procedure of using cryoablation for treating these patients. Lesions are created in the right atrium of the heart using the company's proprietary cryoablation catheter, which reaches temperatures as low as minus 90 degrees Celsius. CryoCor said it expected to complete patient enrollment by year-end. Upon successful completion of the feasibility study, the company expects to file for approval early this year to proceed with a U.S. pivotal trial to support a premarket approval application.
Cyberonics (Houston) has been assigned royalty free rights to U.S. patent No. 6,473,644 B1, covering a "Method to Enhance Cardiac Capillary Growth in Heart Failure Patients." The patent includes 41 claims and provides patent protection for vagus nerve stimulation to increase cardiac output. The primary inventor of the patented method is Reese Terry, the company's founder and current member of its board.
Dade Behring (Deerfield, Illinois) said that testing blood for the presence of C-reactive protein, in conjunction with cholesterol testing, could be an important means of identifying persons at risk of developing heart disease, according to a study published in the New England Journal of Medicine. The company said the study is the largest to date on the use of C-reactive protein in cardiac risk assessment, and involved 27,939 women over the mean course of eight years. It reported that "because C-reactive protein and LDL cholesterol measurements tended to identify different high-risk groups, screening for both biologic markers provided better prognostic information than screening for either alone." The levels of CRP associated with increased risk of heart disease are very low, and can only be detected using high sensitivity assays. Dade's N high-sensitivity CRP assay was one of the first such tests in the market. In patients at risk for cardiovascular events, C-reactive protein and low-density lipoprotein (LDL) cholesterol levels are frequently elevated.
EP MedSystems (West Berlin, New Jersey) received FDA marketing clearance for its Alert System, a catheter system used for treating atrial fibrillation. The Alert System delivers programmable low-energy, bi-phasic electrical impulses directly to the inside of a patient's heart to convert atrial fibrillation to a normal rhythm. The electrical impulses are delivered via the Alert catheter, used in tandem with an energy source called Alert Companion. Both the Alert catheter and Alert Companion, as a system, underwent a controlled, randomized clinical trial of more than 150 patients, demonstrating the products' safety and efficacy. The company said it intends to expand the market for its Alert product platform with the submission of the Alert CS/RA product dossier to the European notified body for regulatory approval. The Alert CS/RA Catheter System replaces existing electrophysiology catheters, allowing the EP physician to not only perform routine diagnostic procedures with the patented CS/RA, but also to easily cardiovert atrial fibrillation to normal heart rhythm during the procedure. The Alert CS/RA Catheter System consists of two catheters, each placed within the heart, to be used together during an electrophysiology procedure to treat certain arrhythmias, including atrial fibrillation. The catheters are placed in the coronary sinus vessel and the right atrium to allow the physician to pace, record and cardiovert the heart.
HemoSense (Milpitas, California) said its INRatio PT Monitoring System (INRatio) for patients on oral anticoagulant therapy was granted the CE mark for use by patients in the home. INRatio is a new generation of portable, hand-held analyzers that test and record the clotting time of blood via prothrombin time (PT) testing. The company's product consists of a low-cost meter and disposable test strips geared for point-of care or home use.
Neoprobe (Dublin, Ohio), a developer of oncology and cardiovascular surgical and diagnostic products, reported the commercial launch of the first product in its Cardiosonix portfolio of blood flow measurement products called the Quantix devices. The Cardiosonix Quantix/ND was released in Germany, the UK and Switzerland. The Quantix/ND received CE mark clearance in August and received clearance under a special 510(k) application in the U.S. last week. The Quantix/ND is a noninvasive bedside blood flow measurement system that easily and accurately measures cerebral blood flow. The company said the Quantix/ND is an angle-independent ultrasound probe that is designed to allow neurosurgeons, neurologists, intensive care units and emergency room physicians to non-invasively measure cerebral blood flow in real time. It also can be used for blood flow measurement in vascular labs. Neoprobe said it expected the CE mark clearance process for the Quantix/OR to be completed by year-end 2002 and that it planned to submit an application for 510(k) marketing clearance in the U.S. shortly thereafter.
OmniSonics Medical Technologies (Wilmington, Massachusetts), a developer of products to treat vascular occlusive disease based on its OmniWave technology platform, said it received the CE mark in the European Union for its Resolution 360 Therapeutic Wire. The company received its first CE mark in June for its Resolution System, which delivers low power, acoustic energy 360 degrees around the active length of the wire to rapidly resolve blood clots, or thrombus, into micro-particles smaller than red blood cells. With this second CE mark, OmniSonics said it now can market the Resolution System and 360 Therapeutic Wire in the EU, initially for the treatment of lower extremity thrombotic occlusions and thrombosed hemodialysis fistulae. The Resolution System consists of three main components a generator, handpiece and the Resolution 360 Therapeutic Wire. The single-patient-contact therapeutic wire is designed to target thrombotic material using low-power acoustic energy 360 degrees around its active 20 cm length.
St. Jude Medical (St. Paul, Minnesota) said it received approval from the FDA to reduce the required sample size in its Resychronization Hemodynamic Treatment for Heart Failure Management (RHYTHM) implantable cardioverter defibrillator (ICD) trial. Completion of the study will now require six-month follow-up data on a minimum of 126 patients implanted with an Epic HF Model V-338 ICD. The original investigational plan for the RHYTHM clinical study required follow-up data on a minimum of 276 patients. All other aspects of the RHYTHM study protocol are unchanged, St. Jude said. The company reaffirmed its expectation to complete enrollment in the RHYTHM study early this year and to receive FDA approval of the device in early 2004. The RHYTHM study is designed to test the safety and efficacy of the Epic HF to treat patients suffering from heart failure who are also at risk of dangerously fast heart rhythms. The Epic HF delivers 30 joules in a compact, physiologic-shaped 36 cc, 73 gram device, which St. Jude said makes it the world's smallest high-voltage cardiac resynchronization device. It said the small size is designed to ease implantation and improve patient comfort and cosmetic appearance. The Epic HF Model V-339 is currently available in Europe in a limited market release.
Volcano Therapeutics (Laguna Hills, California), an early-stage medical device company, said the U.S. Patent and Trademark Office has issued a new patent covering methods of identifying vulnerable plaque through the use of intravascular thermography. Volcano Therapeutics is focused on the discovery, development and commercialization of products for the detection and treatment of vulnerable plaques located in the coronary or peripheral arteries. U.S. patent No. 6,475,159 broadly covers methods for the use of intravascular thermography to detect vulnerable plaque lesions, the company said.
WorldHeart (Ottawa, Ontario) said it has requested Health Canada approval to use an ePTFE inflow conduit as an alternative option for its Novacor LVAS (left ventricular assist system). The conduit has been approved for European use and is now under review by the FDA in the U.S. The inflow conduit carries blood from the natural heart to the Novacor LVAS, which then pumps the blood into the aorta to assist a failing heart. The conduit, developed by WorldHeart, uses expanded polytetrafluoroethylene (ePTFE) graft material. "We know that Canadian physicians have been eagerly waiting the availability of the ePTFE conduit, since it has decreased the possibility of complications from stroke to less than 10% in European use," said Tofy Mussivand, chairman and chief scientific officer. "We expect sales for Novacor LVAS to approximately double over the next five quarters, reflecting expansion in active implant centers and anticipated approval of the ePTFE conduit in the U.S. and in Canada," added Rod Bryden, president and CEO. Novacor LVAS is an electromagnetically driven pump that provides circulatory support by taking over part or all of the workload of the left ventricle. In Europe, the device has unrestricted approval for use as a bridge to transplantation, an alternative to transplantation and to support patients who may have an ability to recover the use of their natural heart
Zoll Medical (Burlington, Massachusetts), a manufacturer of noninvasive cardiac resuscitation devices providing both pacing and defibrillation, reported receiving approval from Health Canada for its AED Plus. Zoll said the automated external defibrillator (AED) is the first to feature a combination of simple, step-by-step illustrations and audio coaching making a stressful medical crisis more manageable and controlled for laypersons assisting victims of sudden cardiac arrest. Richard Packer, president and CEO, said, "We expect the AED Plus to fuel continued growth in our Canadian market." The AED Plus features a single electrode pad easily positioned on the body (compared to other AEDS using two pads), the company said, noting it is the first AED to run on consumer batteries. The AED Plus incorporates Zoll's Rectilinear Biphasic waveform, which is labeled as clinically superior to monophasic defibrillators for conversion of ventricular fibrillation in high-impedance patients and for cardioversion of atrial fibrillation.