Continuing its rapid pace of product approvals, Guidant (Indianapolis, Indiana) last month received the FDA's okay for the newest iteration of its cardiac resynchronization therapy defibrillator (CRT-D) the Contak Renewal 3 system. The Renewal 3, an implantable device that combines a pacemaker to help regulate a patient's heartbeat with a defibrillator aimed at resuscitating patients with dangerously fast heart rhythms, is the fourth Guidant CRT-D device that U.S. regulators have approved in a little over a year. The company received formal approval of its Contak CD/EasyTrak system in May 2002 after an initial rejection by the FDA's Circulatory Device Systems Panel in July 2001. The next generation of that device, the Contak CD 2, received U.S. approval in October 2002 and the Renewal achieved clearance in January of this year.
"Physicians appreciate [our] CRT-D flexibility in tailoring therapy for their patients. The Renewal 3 CRT-D offers this advantage as well as a full suite of diagnostic and therapy options in a smaller, physiologic teardrop shape," said Fred McCoy, president of Guidant's Cardiac Rhythm Management unit.
Chris Hartman, manager of the heart failure marketing department for Guidant, told Cardiovascular Device Update that the new device would be introduced sometime this quarter.
The Renewal 3, like its Renewal cousin approved earlier this year, is specifically designed for heart failure patients and is placed beneath the skin, near the collarbone, to monitor heartbeats and assist as needed. It delivers small electrical impulses that may improve the timing of the heart and its pumping ability. Guidant's Renewal family includes the first and only CRT-D devices commercially available in the U.S. that use independent sensing and independent electrical stimulation to deliver appropriate therapy to both the left and right ventricles of the heart. Rival Medtronic (Minneapolis, Minnesota) is the only other company with a similar device on the U.S. market. Its InSync ICD received FDA approval in June 2002, a month after Guidant's original Contak CD clearance.
Nearly 22 million people worldwide, including approximately 5 million Americans, suffer from heart failure. Additionally, nearly 1 million new cases of heart failure are diagnosed annually worldwide.
Hartman said the company has improved the Renewal 3 in the three areas that matter most to patients "the size of the device, the shape of the device and the longevity, and we've raised the bar on every one of these fronts." It features independent channels and, at 37 cc in volume and 11.5 mm in depth, is the smallest and thinnest CRT-D available on the U.S. market today. The company said the system's physiologic teardrop shape also makes the device easy to implant. Hartman said the longevity of the device has improved significantly from 4 years for the original Renewal system to six years for the Renewal 3.
The Renewal 3 CRT-D family also includes a high-energy option for patients who require additional energy to resume normal heart rhythm, the only company to offer this high-energy option in the U.S. "Our standard energy has always been 31 joules and now we'll offer a 41 joule variant as well of the Renewal 3," Hartman said. "These patients have pretty sick hearts. It's a little unconventional in terms of traditional defibrillation. You're dealing with a bigger heart, bigger surface area. The vectors are kind of awkward sometimes and so a lot of physicians say some of these hearts just call for a little more energy."
As with other Renewal CRT-D systems, this device includes Guidant's Heart Rate Variability (HRV) Monitor Footprint, a way to visualize the patient's heart rate and frequency over the previous 24 hours. The HRV Monitor Trending feature enables the physician to monitor a heart failure patient's cardiac activity over time. The device also includes the company's Ventricular Rate Regulation (VRR) feature, which is designed to maximize the delivery of resynchronization therapy in the presence of atrial fibrillation.
Guidant also reported receiving FDA market clearance for its Vitality DS implantable cardioverter defibrillator (ICD) system, calling it "the world's smallest dual-chamber ICD." The Vitality DS system is designed to treat patients with life-threatening rhythms in the lower chambers (ventricles) of the heart, the most common cause of sudden cardiac death. Patients with cardiac arrhythmias can experience symptoms such as palpitations, dizziness, lightheadedness or fainting because the heart is beating too fast to circulate blood effectively. This electrical malfunction of the ventricle can result in collapse and sudden cardiac death unless medical help is provided immediately. The Vitality DS ICD, implanted under the skin near the collarbone, continuously monitors the patient's heart rhythm and delivers electrical therapy when needed to protect against sudden cardiac death.
In yet more new-product news, Guidant reported the European market launch of the Insignia Ultra line of pacemakers. The Insignia Ultra pacemaker includes a new feature that combines the enhanced security of beat-to-beat pacing verification with the ease of one-button programmability. Guidant's Automatic Capture feature looks at every beat to see if the lower chambers of the heart contracted in response to the delivered pacing pulse from the device. If no contraction is detected, a backup pace with more energy is issued to ensure contraction. This allows the pacemaker to operate at lower energy levels to optimize energy delivery. The Insignia system's teardrop shape and smaller size give the device a more physiologic dimension intended to facilitate easier insertion during implant.
Elsewhere in the product pipeline:
Agenix Ltd. (Brisbane, Australia) said it has made a "significant breakthrough" in the detection of blood clots at Royal Brisbane Hospital. The company's blood clot imaging agent, ThromboView, detected a deep vein thrombosis of a patient as part of a Phase Ib clinical trial. In a parallel clinical Phase Ia trial in healthy volunteers completed earlier, ThromboView was shown to date to be safe and well tolerated. The current patient-based Phase Ib trial is designed to determine the safety and tolerability of ThromboView in patients with blood clots and will also give an indication of the agent's ability to assist doctors detect and image blood clots. In both the healthy volunteer trial and in the first patient included in the new trial, the performance of ThromboView continues to meet expectations, the company said. The current trial is anticipated to enroll patients with confirmed deep vein thrombosis at four Australian sites.
AntiCancer (San Diego, California) said its A/C Diagnostics unit has received FDA clearance to market the A/C Enzymatic Homocysteine Assay. The new homocysteine assay uses a genetically engineered enzyme specific for homocysteine. The assay will be able to serve the need for widespread testing for homocysteine, a risk factor for cardiovascular and other diseases.
ATS Medical (Minneapolis, Minnesota) reported that its Open Pivot Heart Valve was the focus of three studies at the 2nd Biennial Meeting of the Society of Heart Valve Disease in Paris this summer. G.J. Van Nooten, MD, of University Hospital (Ghent, Belgium), presented a 10-year follow-up and comparison of aortic valve recipients maintained on lower levels of anticoagulation, offering insights into anticoagulation management of valve recipients within selected criteria. Excellent hemodynamic performance was the highlight of a presentation by Saed Jazayeri, MD, of Dijon University Hospital (Dijon, France), reporting on a blinded evaluation of 100 patients who had received the ATS AP (Advanced Performance) aortic valve. The results of a five-year follow-up of patients randomized to the ATS Open Pivot Heart Valve or to the industry standard St. Jude Medical (St. Paul, Minnesota) valve were the subject of a presentation by Lex van Herweden, MD. Multiple surgeons and centers in the Netherlands prospectively randomized 567 patients to the valves, with the result showing that, as a group, the ATS valve recipients exhibited a favorable thromboembolic complication rate of .6% per patient year vs. .9% for the St. Jude Medical cohort. ATS said the results support the conclusion that its valve offers clinical performance at least comparable to currently acknowledged standards.
Cambridge Heart (Bedford, Massachusetts) said the results of a study assessing the utility of Microvolt T-Wave Alternans in predicting risk of sudden death among MADIT II type patients have been reported in The Lancet. The results indicate that the MTWA Test, using the Cambridge Heart proprietary Analytic Spectral Method during exercise stress, identifies which MADIT II type patients are at low risk for sudden cardiac death and therefore may not benefit from implantation of a defibrillator. MADIT II type patients are people who have had a previous heart attack and have diminished heart function as measured by left ventricular ejection fraction (LVEF less than or equal to 0.30). The study identified 129 MADIT II type patients from two previously published clinical trials which prospectively evaluated Microvolt T-Wave Alternans testing in a larger population of 957 heart patients. Some 27% of the MADIT II type patients tested MTWA negative, while 73% were non-negative. The primary endpoint of the study was sudden cardiac death and cardiac arrest. Kaplan-Meier analysis at 24 months of follow-up revealed an event rate of zero for patients who tested MTWA negative and an event rate of 15.6% for the remaining patients. Thus, there were neither sudden cardiac deaths nor cardiac arrests among the MADIT II-type patients who tested MTWA negative.
Cardiac Science (Irvine, California) reported the launch of two new portable public access defibrillators (AEDs) the Powerheart AED G3 and the FirstSave AED G3. The new AEDs, which share the same technology platform, differ in features, price and warranty and will address the varying needs of customers in the corporate, municipal, home and medical markets. The G3 line offers customer-friendly features such as one-button operation and RescueReady technology to ensure reliability. They also incorporate the company's patented RHYTHMx analysis software and STAR biphasic shocking engine. The new products are currently in production and the company anticipates delivery to international customers and distributors this month. Shipments in the U.S. will begin upon receipt of marketing clearance by the FDA.
Cardima (Fremont, California) reported receipt of the CE mark for its Revelation Helix STX therapeutic microcatheter to treat atrial fibrillation originating in the pulmonary veins. The Revelation Helix STX, or "large loop" version of the Revelation Helix, provides a larger loop diameter that may enable ablation within larger diameter pulmonary veins, or ablation at the pulmonary vein-left atrium junction. The new microcatheter has several features that distinguish it from the current line of Cardima products and make it a better alternative for certain patients. Its 16 short (3 mm in length), fine wire electrodes allow for greater radial hoop pressure, better tissue contact and an enhanced current density effect.
CryoCath Technologies (Kirkland, Quebec), a developer of cryotherapy products to treat cardiovascular disease, last month received the CE mark for CryoVasc, a catheter for the treatment of chronic cardiac ischemia. The company said that CryoVasc is the sixth cardiac product it has commercialized in Europe. The European approval follows a key U.S. method and device patent issued in June, providing the company with broad coverage for its cardiac ischemia program. "A major commercial opportunity exists for a safe and effective therapy for chronic ischemia. This announcement allows us to efficiently move forward with international thought leaders to ultimately position CryoVasc as a best-in-class solution," said Steve Arless, president and CEO. "This approval also highlights our longer-term corporate strategy of augmenting our growing franchise in the field of cardiac ablation with other high-growth opportunities in interventional cardiology," he told CDU. CryoVasc is a steerable 7 Fr catheter used to deliver cryotherapy in the range of -20 degrees C to -80 degrees C to trigger the formation of new arteries (arteriogenesis), the type of blood vessel that carries oxygenated blood to the cardiac tissue. The CryoVasc, "like the laser catheters goes into the left ventricle and can stimulate, through these controlled freezes, the release of growth factors that causes the growth of new blood vessels," Arless said, calling the technique a form of mechanical angiogenesis. He said the company was inspired to use cryo in the treatment of ischemia by observing its application by such companies as CardioGenesis (Foothill Ranch, California) and PLC Systems (Franklin, Massachusetts) who use lasers to create tiny channels in the heart muscle to trigger the mechanisms of angiogenesis.
Curis (Cambridge, Massachusetts) said that a medical research group has demonstrated that a key signaling pathway, controlled by the Hedgehog protein, plays a crucial role in promoting the development of new blood vessels following tissue injury. The research points to potential therapeutic applications for the Hedgehog pathway in the treatment of a variety of vascular disorders. The scientific report, titled "Postnatal Recapitulation of Embryonic Hedgehog Pathway in Response to Skeletal Muscle Ischemia," was published last month in the journal Circulation. The research, conducted by Dr. Douglas Losordo and his colleagues at Saint Elizabeth's Medical Center (Boston, Massachusetts), demonstrated that the Hedgehog pathway is activated after tissue damage and controls the formation of new blood vessels. Curis said it has recently developed drug-like small molecules that can either turn the Hedgehog pathway on or off. This research validates its core technological approach to drug development, the company said.
diaDexus (South San Francisco, California) said the FDA has granted the company marketing clearance for its PLAC test. This test is cleared as an aid in predicting an individual's risk for coronary heart disease, in conjunction with clinical evaluation and patient risk assessment. The PLAC test measures the level of lipoprotein-associated phospholipase A2 (Lp-PLA2) in human blood. Lp-PLA2 is an enzyme that has been identified as a novel risk factor for coronary events.
Medtronic Physio-Control (Redmond, Washington) and Medusa Medical Technologies (Halifax, Nova Scotia) reported that they have formed a strategic partnership to market and develop electronic patient data reporting systems for the EMS (emergency medical services) market that allows easier and more accurate patient data capture, transfer and analysis. The Siren ePCR Suite from Medusa is an electronic patient care reporting and data management system. It can be linked directly to Lifepak monitor/defibrillators from Medtronic Physio-Control for automatic capture and transfer of cardiac rhythm and vital signs. Both companies will adapt existing products to work more closely together and in the future will jointly develop new products for the EMS customer. The first products are expected to be available this year.
Quest Diagnostics (Teterboro, New Jersey) said that it has begun to offer a test to enable physicians to detect a new risk factor for cardiovascular disease by measuring levels of the enzyme Lp-PLA2 (lipoprotein-associated phospholipase A2). Elevated levels of Lp-PLA2 indicate that a patient is at an increased risk of suffering a cardiovascular event, such as a heart attack. In some cases, this test identifies patients who do not have other apparent risk factors. The Lp-PLA2 test is designed to be used in conjunction with clinical data and other diagnostic markers. The company performs the test under an agreement with diaDexus (South San Francisco, California).
SHL Telemedicine (Tel Aviv, Israel), developer and supplier of remote monitoring solutions for medical applications, launched a new blood-testing device for the early diagnosis of heart attack at home called TeleMarker that promises to prevent millions of unnecessary visits to the emergency room each year by patients with complaints of chest pain. The technology can perform enzyme tests usually requiring a laboratory and transmit the results via telephone connection to a monitoring center, a physician's office, or hospital. The first target of SHL's technology is the home market in Israel, where the company serves more than 70,000 subscribers. SHL Telemedicine co-president Erez Alroy said, "The TeleMarker helps focus emergency treatment before the patient has arrived in the ER, or, can help avoid previously unavoidable false hospitalizations based on patients' verbal reports alone." SHL said that preliminary diagnosis of acute myocardial infarction "is usually based on two out of three positive indications: description of symptoms, ECG changes or elevated enzymatic cardiac markers. All of these can be transmitted by the TeleMarker from the subscriber's home."
St. Jude Medical (St. Paul, Minnesota) reported initial patient enrollment in the QuickSite Lead Phase of the RHYTHM (Resynchronization Hemodynamic Treatment for Heart Failure Management) ICD Study. The study will evaluate the safety and efficacy of the QuickSite left ventricular lead system (Model 1056K) in an ICD indicated patient population with advanced heart failure (NYHA class III or IV) and cardiac dyssynchrony indicated by a QRS duration greater than or equal to 130 ms. The QuickSite lead uses two types of insulation in the lead body: polyurethane (55D) designed for enhanced mechanical properties (pushability and torquability during lead placement) and silicone on the distal segment designed for flexibility and steerability. A unipolar left ventricular pacing lead, it is designed for use with implantable pulse generators for long-term cardiac pacing and sensing. The lead features an over-the-wire design that enables implantation using either a guidewire or stylet in the coronary veins overlying the left ventricle of the heart. The distal portion of the QuickSite lead is pre-shaped into an "S" curve to provide placement stability. It uses a titanium nitride coated platinum-iridium electrode and steroid-eluting collar designed for optimum threshold performance. Fast-Passcoating covers the outer lead body to increase lubricity during implantation, St. Jude said.
Thoratec (Pleasanton, California) said it has received European marketing approval for the Thoratec IVAD, an implantable heart pump that helps support one or both chambers of the heart. The device is a smaller, implantable version of the company's ventricular assist device or VAD, which typically rests outside the patient's chest with tubes connected to the heart. Both devices support heart function and blood flow in late-stage heart failure patients who are awaiting heart transplantation or recovering from open-heart surgery. At less than a pound, the IVAD is the smallest commercially available implantable VAD device, the company said. The approval follows a clinical trial involving 17 patients in Europe. A similar trial is currently under way in the U.S., and the company hopes to seek U.S. regulatory approval later this year.
Vasogen (Mississauga, Ontario) began enrollment early last month in its pivotal Phase III ACCLAIM trial to evaluate its immune modulation therapy in reducing mortality and morbidity in advanced chronic heart failure patients. The study, which will enroll up to 2,000 patients at 100 leading U.S. and Canadian cardiac centers, will conclude when a minimum of 701 events have occurred and all patients have been followed for at least six months. Its primary endpoint is the composite endpoint of all-cause mortality or hospitalization for cardiovascular causes.