The beat goes on for Medtronic (Minneapolis, Minnesota) which last month received FDA approval for its InSync ICD (implantable cardioverter defibrillator) system for heart failure received FDA approval, a little over four months after winning a narrow 6 to 5 vote for recommendation of approval from the agency's Circulatory Systems Devices Panel. The approval provides the medical device powerhouse with yet another therapeutic option for the potentially hundreds of thousands of people who suffer from one of the most rapidly growing forms of cardiovascular disease.
The new system is approved for the treatment of heart failure patients who have ventricular dysynchrony and who are also at risk for potentially lethal ventricular arrhythmias that could lead to sudden cardiac arrest. In patients diagnosed with heart failure, sudden cardiac arrest occurs at six to nine times the rate of the general population.
The InSync ICD combines the InSync pacemaker, which sends electrical pulses to help failing hearts pump more efficiently, with a defibrillator to shock irregular or rapid heartbeats back into rhythm. People suffering from heart failure are six to nine times more likely to suffer sudden cardiac arrest than the general population. In the company's latest earnings release, it said sales of the original InSync device – approved for the treatment of heart failure in August 2001 – were running at an annual rate of $300 million. That device, which does not include the defibrillator that is integral to the newly approved system, has been one of Medtronic's most successful launches to date.
Those FDA panel members who voted against recommending the device at the March meeting said the company's data was too incomplete, or they expressed concerns that the wires connecting the implant to the heart would become dislodged. But data released later that month from the MIRACLE ICD trial – for Multicenter InSync Randomized Clinical Evaluation ICD – presented at the American College of Cardiology (ACC; Bethesda, Maryland) scientific sessions in Atlanta, Georgia, demonstrated that many patients with moderate to severe heart failure who received the InSync ICD system experienced an improved quality of life, increased functional capacity and better exercise tolerance with the device.
Those results were presented by Jacob Young, MD, director of the Kaufman Center for Heart Failure at the Cleveland Clinic Foundation (Cleveland, Ohio), a co-principal investigator in the trial. In the study, 362 patients with moderate-to-severe heart failure and poorly timed ventricular contractions were implanted with the ICD device. The patients were then randomized to have the resynchronization feature turned either on or off. The data revealed that more patients in the treatment group experienced quality of life (QOL) improvement those in the control group, as measured by the Minnesota Living with Heart Failure Questionnaire. The QOL score decreased 19 points in the treatment group, compared with 10 points in the control group. Young said that these improvements exceed similar measurements of advanced heart failure patients using such standard medications as beta-blockers and ACE inhibitors.
A marked improvement in New York Heart Association (NYHA) functional class also was observed in the treatment group. Compared to baseline, 63% of patients in the ICD-on group experienced an improvement in NYHA functional status by one or more class at six months, compared to 47% in the control group.
The third endpoint, six-minute hall walk distance, failed to show statistically significant differences (56 meters in the treatment group vs. 53 meters in the control group). However, the researchers noted statistically significant improvements in exercise capacity. There was an improvement in Peak VO2, which measures the body's ability to take in oxygen needed for daily activities. The treatment group increased 1.1 ml/kg/ min, compared to no change in the control arm. Additionally exercise time data also showed that the treatment group increased exercise duration by nearly a minute (58 seconds), while the control group's time actually decreased by 26 seconds.
"Heart failure is not necessarily a death sentence," said Young. "On the contrary, the InSync ICD system allows heart failure patients to live better, more active lives with the added peace of mind in knowing that their device will also protect them against potentially deadly heart rhythms."
Medtronic said that with the addition of this most recent approval to its arsenal, it is the only company with two FDA-approved cardiac resynchronization systems that address specific segments of heart failure patients – those who require resynchronization therapy alone, and those who require resynchronization therapy along with sudden cardiac arrest protection. The company also said that out of the approximately 750,000 people who are candidates for the already-approved cardiac resynchronization therapy provided by the InSync system, at least 100,000 have a ventricular arrhythmia indication and could benefit from the ICD system.
The Medtronic device will compete with Guidant's (Indianapolis, Indiana) Contak CD and EasyTrak lead system, which finally gained FDA approval in May after initially being turned down by an FDA panel in July of last year. The devices are similar. Both help the chambers of the heart beat in a coordinated manner and give a jolt to correct potentially life-threatening rapid heart rhythms.
Jan Wald, who covers the healthcare sector for A.G Edwards & Sons (St. Louis, Missouri), said he expects Guidant and Medtronic to split market revenue pretty evenly. He said he thinks one key factor, marketing muscle, will go to Medtronic, while the other key factor, ease of use, at this point goes to Guidant. "With [these two devices] we're looking for a total market of about $350 million to $400 million in the first 12 months and then expanding to about a $3 billion or $4 billion market over the next four or five years," he added.
Generally echoing Wald's viewpoint was Larry Haimovitch, president of Haimovitch Medical Technology Consultants (Mill Valley, California), who covers the cardiovascular sector for Cardiovascular Device Update. "Now the fun begins," he said. "They're neck and neck at this point. I don't think there is any reason to think that one or the other is going to dominate." However, he did note that Guidant most needs the ICD market to work, especially after its recent string of bad luck in the coated-stent sector.
Elsewhere in the product pipeline:
Camtronics Medical Systems (Hartland, Wisconsin), a subsidiary of Analogic (Peabody, Massachusetts), unveiled a new release of its Vericis PhysioLog Hemodynamic Monitoring and Data Management System that features patient data collection, waveform visualization, and customizable management reports. According to Camtronics, the new system marks a new level of functionality and performance in hemodynamic monitoring and data management. The new release of PhysioLog, which recently received FDA market clearance, features a new table rail-mounted, compact patient data module that integrates 12-lead ECG, respiratory rate, two to four invasive pressures, NIBP, SpO2, thermodilution cardiac output and a programmable ECG or invasive pressure analog output. The company said the new waveform visualization software gives clinicians the flexibility to view pressures, respiratory rate, ECG waveforms and thermodilution cardiac output in multiple formats or on one easy-to-read screen. The standards-based Vericis platform integrates data from different sites (physician office, clinic, hospital) and different sources (interventional and diagnostic X-ray angiography, echocardiography, nuclear cardiology, MR, hemodynamics, reports, HIS) to create a comprehensive digital record on the cardiac patient.
Cardima (Fremont, California) said that six-month follow up on 80 patients enrolled in its Revelation Tx trial to treat atrial fibrillation (AF) has been completed, and that 97% of patients using the Revelation Tx microcatheter system experienced a reduction of at least 50% in their episodes of AF. Cardima said the preliminary data indicates that half of the patients experienced no recurrence of AF episodes. The Phase III pivotal study of paroxysmal AF was initiated in October 2000. In April 2001, Cardima said that the FDA had accepted a modular filing of its PMA application and had designated five modules, with the fifth module including clinical results from patients enrolled in the trial. The four preclinical modules already have been submitted, three of which have been accepted and closed by the FDA. Cardima said Phase I and II data with the single-use Revelation Tx microcatheter system have demonstrated safety and promising efficacy. The company is targeting FDA approval for the product by year-end. The Revelation Helix product received CE mark approval in December 2001 and was launched in the European Union in 1Q02.
CardioFocus (Norton, Massachusetts) received FDA permission to begin a Phase I trial of its Light Ring catheter to treat atrial fibrillation (AF). The Light Ring catheter uses infrared laser light to treat AF in patients who have been resistant to drug therapy. Up to 20 patients are expected to be enrolled in the multicenter protocol, initially at three U.S. centers. Additional patients will be enrolled in Europe and Canada to support product registration in those markets. Some clinical centers use radiofrequency (RF) catheters to treat AF by targeting the pulmonary veins, which attach to the left atrium. These procedures require many applications of RF energy, are very time consuming and have had moderate success. But CardioFocus said the Light Ring catheter uses infrared laser light to treat the entire pulmonary vein in a single application of energy.
CardioGenesis (Foothill Ranch, California), a developer of transmyocardial revascularization (TMR) and percutaneous myocardial revascularization (PMR), presented at the International Society of Minimally Invasive Cardiac Surgery meeting in New York, data from a TMR study using its Holmium:YAG laser was. It involved 45 patients with advanced coronary artery disease and suffering from severe angina who could not be completely revascularized and therefore underwent TMR with the Holmium:YAG laser. Fourteen had previously been treated with a catheter or bypass procedure or both. The TMR-treated patients were followed up over an average period of 1.7 years and angina relief was found to be profound and sustained, with 95% angina free and not taking antianginal medications. The study also revealed that based on an improvement in lifestyle questionnaire, 93% were rated in the highest category (very good) following the procedure, with 94% saying they would recommend the procedure to others in similar circumstances. TMR and PMR are related procedures in which physicians use lasers to create small channels in the heart muscle to trigger the mechanisms of angiogenesis, or the creation of new blood vessels in the heart. The FDA approved TMR, a surgical version of the procedure, in 1999. PMR is a catheter-based version of the procedure not yet cleared by the FDA but CE-approved.
Cordis (Miami Lakes, Florida), a unit of Johnson & Johnson (New Brunswick, New Jersey), said the FDA has given it approval to market the Bx Sonic Over-the-Wire Coronary Stent. The product is indicated for improving coronary luminal diameter in patients with symptomatic ischemic heart disease due to de novo and restenotic lesions in native coronary arteries with reference diameters from 3.0 mm to 5.0 mm. The stent also is indicated to treat abrupt or threatened vessel closure in patients with failed interventional therapy in lesions with reference diameters from 2.25 mm to 4.00 mm. The self-centering tip design of the stent is engineered to facilitate smooth navigation and delivery in tortuous anatomy and challenging lesions. The catheter uses the company's DirectSeal Sealing Process, engineered for improved crossability, providing seamless tip-to-balloon transition to cross challenging lesions more successfully, according to the company. Additionally, the system contains a new, shorter balloon made with Duralyn semi-compliant balloon material with minimal overhang, designed to reduce the risk of edge dissection. To meet the challenges of small, medium and large vessel sizes, the stent is engineered with six-, seven- and nine-cell support structures.
CryoCath Technologies (Montreal, Quebec) received FDA acceptance of the first of five modules of its PMA filing for the Freezor Cardiac Cryoablation system. The module contained pre-clinical data that demonstrated the safety and efficacy of the system in the animal model. Steven Arless, president and CEO of CryoCath, said, "Having already filed the next three modules, we are well-positioned to receive PMA approval by the third quarter of 2003." He said the final module will be based on data to be finalized and filed by September. Modules two through four provide information on biocompatibility, bench testing data and manufacturing. The fifth module will be based on data from CryoCath's FROSTY Pivotal Study of 165 supraventricular tachyarrhythmia (SVT) patients using the company's minimally invasive, catheter-based 7 Fr Freezor Cardiac CryoAblation System. CryoCath is developing additional products, including the Arctic Circler and FrostLine, to treat tachyarrhythmia. Separately, the company reported the first U.S. commercial use of its SurgiFrost CryoSurgical Probe System to treat cardiac arrhythmias on two patients at St. Joseph's Hospital and Medical Center (Baltimore, Maryland). One surgeon said that as he performed mitral valve replacements from a transeptal approach, it was easy with the SurgiFrost System to create the additional lesions required to do the complete Maze III lesion set – with epicardial lesions on the left atrium and a combination of epi and endocardial lesions on the right atrium. The system uses an argon-based cooling system with a malleable, single-use cryosurgical probe to surgically treat cardiac arrhythmias, including atrial fibrillation.
Edwards Lifesciences (Irvine, California) received FDA premarket approval for its Carpentier-Edwards S.A.V. porcine replacement heart valve. The Carpentier-Edwards S.A.V. Bioprosthesis allows for a supra-annular implantation – above a patient's native aortic valve, rather than directly into the aortic annulus – and a proprietary scalloped sewing band for optimizing anatomic fit. Supra-annular placement allows surgeons to implant a larger-orifice valve, which provides improved hemodynamic performance over intra-annularly placed porcine aortic heart valves. In conjunction with the launch of the device, Edwards also is introducing a new set of valve sizers, as well as a number of new educational tools to facilitate implantation.
Endovasc (Montgomery, Texas) filed a patent application for a method for stimulating growth of new blood vessels in the heart and limbs by releasing therapeutic amounts of its new drug, Angiogenix, a nicotine acetylcholine receptor agonist, from a stent leading to an ischemic area by the heart or limbs. The company said the stent will be used as the delivery platform, which is first used to open the vessel while the drug stimulates new circulation by causing new blood vessels to grow into the tissue in order to supply fresh blood, oxygen and nutrients. The company said that stents "may provide a much safer and effective method of releasing drugs that stimulate the angiogenesis" than delivery through endocardial catheters. Endovasc has established a joint venture with MIV Therapeutics (Vancouver, British Columbia), which already has chosen the company's PROStent therapeutic as a coating for preventing restenosis, and the PROStent coating process is transferable to Angiogenix coatings.
EP MedSystems (Mt. Arlington, New Jersey) received CE mark clearance for its 30-joule Alert Companion, a biphasic low energy defibrillation device designed for use in conjunction with catheters for internal defibrillation of the heart. Additionally, the company said the current Alert Companions in use could be upgraded for an energy output of 30 joules from the current energy output of 15 joules. The company said the Alert system has been shown to use about 50 times less energy for cardioversion than the standard external paddles.
Hemonix (Beaverton, Oregon) presented a new noninvasive blood pressure monitoring technology at the American Society of Hypertension conference in New York. The new monitor and cuff, called the Hemo View PeriVasc (for peripheral vascular), utilize electrical bioimpedance and a disposable sensor attached to a standard blood pressure cuff to measure central venous pressure as an alternatives more invasive catheter procedures. Hemonix reported conducting clinical trials at the Veterans Affairs hospital in Portland, Oregon, and at sites in Atlanta, Georgia, and Los Angeles, California, with results described by the company as "encouraging."
Instromedix (San Diego, California), a business of Card Guard (Schaffhausen, Switzerland), is launching the King of Hearts Express AF, a 30-day cardiac event monitor with atrial fibrillation (AF) auto-trigger capabilities. Along with being able to store patient-activated events, the Express AF automatically detects and records diagnostically important episodes of AF (including asymptomatic events). The company said that cardiac event monitors allow physicians to extend the monitoring period to 30 days and can increase the diagnostic yield more than 90% over traditional Holter monitoring. Even higher yields are expected with the addition of auto-trigger technology. Instromedix is a developer of telecardiology, specializing in noninvasive, portable cardiac event monitoring and pacemaker follow-up systems.
International Medical Innovations (IMI; Toronto, Ontario) said the FDA approved its Cholesterol 1,2,3 test, which is designed to measure skin cholesterol in adults with severe coronary artery disease (CAD). Other tests currently used by clinical laboratories measure cholesterol from blood samples. IMI said that while the approval of the test is significant, the product is not approved for routine screening. According to the FDA, the test is for people suspected of having severe CAD (defined as 50% closure of two or more arteries) and those with a history of heart attack. The test is intended for use along with – not as a substitute for – standard blood tests. Additionally, it cannot substitute for an evaluation of other risk factors used to identify the risk of CAD. The company said that the test, while effective by itself, works best in tandem with the available technology, based on the data IMI collected for its trials. The test contains a foam pad with small holes in it that is placed on the palm. To this, a droplet of an enzyme-containing liquid, followed by a drop of another chemical, is added. Within three minutes the pad will turn different shades of blue, depending on how much cholesterol is detected. A handheld device translates the color shade into numbers that, considered together with traditional tests, translate into different levels of risk. The scale for the test ranges from about 60 or 70 on the low-risk end of the spectrum to about 200 on the high-risk side. The cutoff between normal and high risk is about 135.
Novoste (Norcross, Georgia) received FDA investigational device exemption (IDE) approval to begin the Beta Radiation for treatment of Arterial-Venous graft Outflow (BRAVO) clinical trial, a randomized, multicenter, placebo-controlled study investigating the safety and efficacy of its Corona System to treat venous outflow stenosis in arterial-venous dialysis grafts. Approximately 230 patients will be enrolled at more than 20 centers in North America and Europe. More than 200,000 people in the U.S. currently undergo long-term dialysis for end-stage renal disease, and a majority rely on arterial-venous dialysis grafts for vascular access. However, these grafts are associated with patency rates of 40% to 60% at one year, and patients often require interventional therapy. There is evidence that the low patency rate is due to proliferation of cells at the graft site, and early clinical data suggests that intravascular radiation may play a significant role in improving patency rates, according to the company. Novoste's Beta-Cath brachytherapy system is commercially available in the U.S., European Union members and several other countries.
PLC Systems (Franklin, Massachusetts), a developer of carbon dioxide (CO2) laser revascularization technology used to treat patients with severe angina said a study published in the June 15 issue of the American Journal of Cardiology confirmed previous safety and effectiveness results of transmyocardial revascularization (TMR). Over six years, more than 300 TMR procedures were performed at the Washington Hospital Center (Washington), after which long-term follow-up demonstrated that patients with small vessel disease receive a more complete revascularization when TMR is combined with coronary artery bypass than bypass alone. Relief from angina was significantly improved at three, six and 12 months compared to preoperative statistics. Preoperatively, 152 patients (90%) had class III or IV angina compared with five patients (3%) at three months and seven patients (4%) at six and 12 months. Also, 82% of the patients in the study had previously been evaluated by other hospitals that perform heart surgery, and had been turned down as inoperable due to small vessels or diffuse disease.
Possis Medical (Minneapolis, Minnesota) filed an investigational device exemption supplement with the FDA to introduce a microcatheter into the TIME 1 IDE clinical trial for ischemic stroke. The study aims to characterize the safety and efficacy of the AngioJet NV 150 catheter in removing blood clots that cause ischemic stroke from the middle cerebral artery of the brain. The AngioJet NV 150 catheter is delivered to the site of the blood clot through a microcatheter, which then serves as the evacuation lumen for the AngioJet System. Until the introduction of the Possis microcatheter, the TIME trial had used the NV 150 with a commercially available microcatheter, but there were certain incompatibilities within that pairing, the company said. It said that the combination of the NV 150 catheter and the Possis microcatheter specifically designed to work with it will provide a higher degree of access to patient treatment sites, as well as a more consistent performance profile. Possis has suspended enrollment into the TIME 1 trial pending FDA approval to introduce the microcatheter and said it expects to restart enrollment early this fall.
Qmed (Laurence Harbor, New Jersey) began its initiative for coronary artery disease in the Medicare Coordinated Care Demonstration (MCCD) project. MCCD will test the feasibility of reimbursing disease management in the Medicare fee-for-service program. It will run for four years, with regular interim evaluations and the possibility of interim expansion based upon success. Qmed's ohms|cvd (On-Line Health Management System for Cardiovascular Disease) combines patient-specific prognosis and national standard therapeutic recommendations for primary care doctors, while incorporating process reports of expense and health outcomes for the managed care organization.
Thoratec (Pleasanton, California) reported implantation of nearly 6,000 of its ventricular assist devices (VADs), including its Ventricular Assist Device System and the HeartMate LVAS (Left Ventricular Assist System). "We believe it represents approximately four times the number of implants than our closest bridge-to-transplant competitor's devices," President and CEO D. Keith Grossman said. "In fact, in the first quarter of 2002 alone, we sold more devices in Europe than our closest competitor expects to sell in Europe in all of 2002." He said nearly 300 patients have been supported by HeartMate devices for a year or longer, including over 30 patients for two years or longer. The company also reported completing three implants of its IVAD, or implantable version of the Thoratec VAD, in its U.S. clinical trial for the device, as a bridge to transplant. The trial will evaluate up to 30 patients in up to 10 centers.
Vascutek (Glasgow, Scotland), a unit of Centerpulse (Zurich, Switzerland) that develops polyester and ePTFE vascular grafts used to treat arterial disease, received FDA clearance for its Gelweave Valsalva graft. The graft is designed for use in the replacement and repair of the root of the aorta, the major artery leading from the heart. This is required when the aorta becomes weak and balloons. It can be used for the treatment of aortic aneurysms and associated valve disease.
Vasomedical (Westbury, New York) said data from a retrospective analysis of its enhanced external counterpulsation (EECP) system presented at the recent annual meeting of the American Diabetes Association (Alexandria, Virginia) showed that the system reduced the frequency and severity of angina in diabetic patients with congestive heart failure (CHF). The one-year clinical outcome study of the International EECP Patient Registry examined outcomes following treatment with EECP in 751 diabetic patients, of whom 267 patients had CHF. On completion of EECP treatment, patients with heart failure and those without heart failure achieved similar reductions in angina severity, frequency of angina episodes and nitroglycerine use. At one-year post-EECP treatment, maintenance of angina improvement was similar in both groups. In other news, Vasomedical said the FDA confirmed that market clearance for use of EECP in congestive heart failure, granted earlier in July, extends to all three of its EECP systems. The initial notification from the FDA specified only the newest EECP Therapy System Model TS3 with integrated oxygen saturation monitoring capability.