SynCardia Systems (Tucson, Arizona), a developer of cardiac replacement and assist devices, in mid-October received final FDA approval for its CardioWest Temporary Total Artificial Heart (TAH-t) – formerly the CardioWest Total Artificial Heart – as a bridge to heart transplantation. Specifically, the approval is for use in cardiac transplant-eligible candidates at risk of imminent death from non-reversible biventricular failure.

The approval came after the company successfully passed an inspection audit inspection of its manufacturing, the final step in a modular filing procedure, said Marvin Slepian, MD, president and CEO of SynCardia and a professor of medicine at the University of Arizona (also Tucson). The company said this is the first FDA approval for a temporary total artificial heart, though the agency, in its "talk paper" announcing the approval, referred to the device as a "partial" artificial heart.

The TAH-t is a pulsating biventricular device implanted into the chest to replace the patient's left and right ventricles, and it is sewn to the patient's remaining atria. By means of tubes through the patient's chest wall, each ventricle is connected to a drive console that provides pulsed pressurized air and enables device monitoring.

One of its antecedents is the original Jarvik heart, but Slepian told Cardiovascular Device Update that there have been a whole range of changes in the device and the selection and handling of patients. Overall, he called the agency approval the culmination of a "40-year project" and the result of "a baton-passing exercise."

The FDA approved the SynCardia device based on a review of clinical studies of safety and effectiveness and the March recommendation for approval by the agency's Circulatory System Devices Advisory Panel. The panel vote was 10 in favor of approval, with conditions, and one abstention. The panel, among the conditions, advised limited use of the device to transplant hospitals, citing the early-stage nature of the technology. Additionally, the panel recommended following patients for one year after implantation of the TAH-t, and the agency is requiring a post-approval study to monitor the device's performance in commercial use.

SynCardia studied the performance of the TAH-t in 81 transplant-eligible patients with severe bi-ventricular heart failure at five U.S. medical centers, and they were compared to a 35-patient control group, but the panelists said that they primarily focused on the single-arm success of the study.

In the study, 79% of patients implanted with the heart remained alive long enough to receive a donor heart – an average of 79 days – demonstrating the device's bridge-to-transplant efficacy. At 30 days post-implantation, 56 of the 81 core group met the criteria for treatment success, which included being ambulatory; judged in New York Heart Association Class I or II categories; not ventilator dependent; and not on dialysis. The longest time that the TAH-t functioned before a patient died or received a transplant was 414 days. Complications included infection (72% of patients), bleeding (42%), neurological event such as major or minor stroke (25%) and device malfunctions (18%). Of the total patients implanted with the device, 17 died before a donor heart became available to them. Results of the study were published in the Aug. 26 issue of The New England Journal of Medicine.

Besides replacing the function of the diseased heart, the TAH-t device helps to restores normal blood pressure and cardiac output, facilitating recovery of end-organ function, such as the kidney and liver. "As a result, patients become better candidates for transplantation," according to a statement from SynCardia.

The dimensions of the heart's console were described by Slepian as a washing machine-sized 2 feet by 3 feet by 3 feet, and SynCardia will next pursue approvals of smaller consoles to enable easier patient mobility. An "intermediate step" console is just 6 inches by 12 inches by 12 inches, and a third will be "backpack" size, weighing only about 10 pounds, he said, and he predicted filings with the FDA for these variations early next year.

The company is positioning the TAH-t in a heart device space between the AbioCor total replacement heart from Abiomed (Danvers, Massachusetts) – which goes entirely inside the chest and needs no external console – and ventricular assist devices (VADs) – small devices supporting the pumping activity of the heart and made by various firms. The AbioCor is a "destination" therapy in cases in which a heart transplant is no longer feasible. On the other hand, Slepian has said that the candidates for the TAH-t have such severe heart failure that they need more assistance than a VAD alone can provide.

About 4,000 patients in the U.S. await heart transplants annually, but only around 2,200 donor hearts typically become available. About 100 of the 4,000 patients awaiting transplants have non-reversible bi-ventricular failure and could be candidates for the new artificial heart, SynCardia has said. Slepian said that the FDA approval "represents a significant milestone in medical history. With the CardioWest TAH-t, we will be able to save the lives of many critically ill patients who are in need of or who are awaiting heart transplants."

Jack Copeland, MD, chief, section of cardiovascular and thoracic surgery at the University of Arizona Sarver Heart Center (Tucson), said, "Over nine years ago, we began collecting research and data on the efficacy of the CardioWest Temporary Total Artificial Heart ... This is a tremendous day, not only for SynCardia but [also] for all people and their families affected by non-reversible biventricular failure."

The TAH-t already is commercialized in France, Germany and Canada. As of the March advisory panel meeting, the company reported the device having been implanted in more than 270 patients worldwide. The heart itself costs from $80,000 to $100,000, with the console priced at around $40,000 – but the latter is a piece of reusable capital equipment, Slepian noted. He said that the cost of the procedure and follow-on care is comparable to a heart transplant procedure, though minus the necessary long-term drug costs required by transplants.

While the patient pool for the heart may ultimately reach into the several thousands, the company will now pursue a slow ramp-up, selling perhaps 20 to 30 of the devices the first year as it develops manufacturing capabilities and trains additional centers in its use, Slepian said. Financially, he said, SynCardia this year has experienced "more black than red, but it's obviously a delicate balance. Our forte has been with research and development and clinical trials; we're not a massive company with tremendous infrastructure and overhead." Thus, he described the company's "ultimate strategy" as partnering with a 'major manufacturer," especially to provide additional assistance with future trials. But, he added, "If that doesn't happen, we're built to last."

Elsewhere in the product pipeline:

The diagnostics division of Abbott Laboratories (Abbott Park, Illinois) has expanded the product offering for its AxSYM automated immunoassay system with an updated test for the detection of cardiac troponin. The company is now ready to market its new AxSYM Troponin-I ADV, which replaces its current troponin test. According to Abbott, the new assay provides initial results within 15 minutes and offers improved detection of cardiac troponin, a protein released from dying heart muscle cells that are deprived of blood flow during a heart attack. The company received 510(k) clearance from the FDA in early September. Development of the updated assay took roughly 16 months, and the company plans to phase out the older test, Abbott said.

AngioScore (Alameda, California) reported receiving the CE mark for its flagship AngioSculpt scoring balloon catheter. The AngioSculpt scoring balloon catheter is a line of coronary angioplasty catheters comprising an angioplasty balloon surrounded by a system of nitinol scoring elements. Creating focal concentrations of dilating force, the scoring elements score arterial lesions as the balloon expands. The AngioSculpt is intended for the treatment of a hemodynamically significant coronary artery stenosis, for the purpose of improving myocardial perfusion.

CHF Solutions (Brooklyn Park, Minnesota) said findings from two clinical trials of Aquapheresis, the company's therapy for fluid overload, were presented as posters at the recent meeting of the Heart Failure Society of America in Toronto. Results of the EUPHORIA (Early Ultrafiltration Therapy in Patients with Decompensated Heart Failure and Observed Resistance to Interventions with Diuretic Agents) trial conducted at Midwest Heart Specialists (Chicago) demonstrated that early treatment with CHF Solutions' Aquadex System 100 facilitated discharge of 68% of hospitalized patients admitted with acutely decompensated heart failure and diuretic resistance in three days or less. In follow-up, none of the patients were readmitted within 30 days and only two admissions occurred within 90 days, one for elective pacemaker implantation and the other for dehydration associated with an incidental infection. The RAPID CHF (Relief for Acutely Fluid Overloaded PatIents with Decompensated Congestive Heart Failure) trial, conducted by the Minnesota Heart Failure Consortium (Minneapolis), is the first randomized trial of ultrafiltration therapy for acute heart failure patients. The results demonstrated that patients hospitalized for CHF treated with a single, eight-hour Aquapheresis session in addition to standard medical therapy achieved significantly greater volume removal 24 hours after enrollment compared to patients receiving standard medical therapy alone. Another trial, UNLOAD (UltrafiltratioN versus IV Diuretics for Patients HospitaLized fOr Acute Decompensated Congestive Heart Failure), is comparing the long-term safety and efficacy of Aquapheresis to conventional intravenous diuretics in hospitalized heart failure patients with fluid overload. The trial will enroll 200 patients at as many as 20 U.S. clinical sites. CHF Solutions expects to announce UNLOAD trial results in 4Q05.

Cordis Endovascular (Warren, New Jersey), a division of Cordis, a Johnson & Johnson company, reported that a patient in Newport Beach, California, is the first to enroll in its surveillance study of its carotid artery stenting system for treatment of patients with carotid artery disease at high-risk for adverse events from carotid endarterectomy. The FDA granted permission to Cordis Endovascular to initiate a surveillance study that will provide ongoing data about the carotid stenting procedure. When fully implemented, the surveillance study will enroll 1,500 patients at 112 sites in the U.S. As part of the study, the FDA also granted permission to the company to launch its comprehensive training program for physicians and other relevant healthcare professionals, called CASES (Cordis Carotid Artery Stenting Education System). Training will include didactic review, case observations and simulation training, and hands-on experience at a regional education center.

Cryo-Cell International (Clearwater, Florida) said that its affiliate, Saneron CCEL Therapeutics (Tampa, Florida), in collaboration with its research affiliates, published promising results using cord blood stem cells in conjunction with stroke in animal models in the October issue of Stroke. Key findings include that stem cells taken from umbilical cord blood, and then given intravenously along with a drug known to temporarily breach the brain's protective barrier, can dramatically reduce stroke size and damage; and when used in the first hours and days following a stroke, stroke size decreased by 40% and the resulting disability was significantly reduced.

CryoCor (San Diego) reported receiving FDA 510(k) clearance for the Breva Surgical Probe, part of its Cardiac Cryoablation System, which includes a control console and a probe/console interface. The Breva Surgical Probe is intended to be used by cardiothoracic surgeons for the treatment of arrhythmias. The device works through cryoablation, the application of extreme cold to ablate or destroy electrically abnormal cardiac and vascular tissue. The Breva Probe will be used under direct visualization to perform cardiac cryoablation procedures in the surgical setting.

diaDexus (South San Francisco, California) said a prospective cohort study of the MONICA population, a landmark 14-year population study, was published in the Oct. 5 issue of Circulation. Data from the study support the measurement of lipoprotein-associated phospholipase A2 (Lp-PLA2) as an independent predictor of individuals at risk for future coronary events. The research team investigated simultaneously the association between plasma concentrations of Lp-PLA2, C reactive protein levels, and long-term risk of coronary heart disease (CHD) in initially healthy middle-aged men. This cohort of the MONICA (MONItoring of trends and determinants in CArdiovascular disease) population includes 934 men, ages 45-64, who originally were surveyed in 1984 from the general population in Augsburg, Germany. In a follow-up study, baseline plasma concentrations of Lp-PLA2 were measured by diaDexus' PLAC test and results were correlated with the 1998 vital statistics on the population. The prospective, full-cohort study established that baseline levels of Lp-PLA2 were higher in the 97 men who developed CHD events than the 837 event-free subjects during the 14-year follow-up period. A one standard deviation increase in Lp-PLA2 was associated with a 37% increase in the incidence of a coronary event.

EP MedSystems (West Berlin, New Jersey) reported that it had received market clearance from the FDA for an enhancement to its EP-4 Computerized Cardiac Stimulator allowing the physician to stimulate the heart using either constant current or constant voltage output. The enhanced stimulator now can be used in both EP (electrophysiology) diagnostic studies of the heart and pacemaker implantations where measuring voltage thresholds are fundamental. The stimulator is integrated with the company's EP-WorkMate Electrophysiology Workstation, as well as other diagnostic technologies used in the monitoring and diagnosis of arrhythmias in the heart.

Guidant (Indianapolis) reported the FDA clearance and U.S. launch of its Vasoview 6 Endoscopic Vessel Harvesting System for extracting vessels used by surgeons to perform coronary artery bypass procedures. The Vasoview 6 system allows the clinician to remove a vein from the leg or an artery from the arm through one small incision. Endoscopic vessel harvesting has been shown to reduce postoperative pain, recovery time, infection rates and scarring, allowing patients to walk sooner and more easily after surgery. Guidant's Vasoview Endoscopic Vessel Harvesting Systems have been used in nearly 400,000 patients to date. The company's sixth-generation Vasoview System incorporates improvements to enhance performance and make the system easier to use.

LuMend (Redwood City, California), a developer of catheter-based technology for crossing chronic total occlusions (CTOs), reported the launch of its Outback Re-Entry Catheter. The company said its proven peripheral crossing technology, the Frontrunner XP CTO Catheter, combines with the Outback Catheter to provide the first system solution that addresses the two major challenges associated with facilitating treatment of CTOs in peripheral arteries: lesion crossing and sub-intimal re-entry. The Outback Re-Entry Catheter is designed to provide a simple and safe re-entry process that quickly redirects a guidewire from the false lumen back into the true lumen of the artery, LuMend said. Once this is achieved, the interventional procedure can continue.

Medtronic Vascular (Santa Rosa, California) reported that it has completed patient enrollment in the ENDEAVOR III clinical trial in the U.S. The data from the ENDEAVOR III trial will be used to support U.S. product approval of the company's Endeavor drug-eluting coronary stent. ENDEAVOR III is a randomized trial evaluating the safety and efficacy of the Endeavor stent vs. the Cypher Sirolimus-eluting stent marketed by Cordis (Miami Lakes, Florida), a Johnson & Johnson company. The equivalency study includes 436 patients (327 receiving the Endeavor stent) with a primary endpoint of in-segment late lumen loss at eight months.

The Philips Medical Systems (Andover, Massachusetts) unit of Royal Philips Electronics reported the launch of a new generation of cardiac ultrasound equipment with high-definition imaging and on-cart data analysis tools. The iE33 intelligent echocardiography system features high levels of 2-D image quality, 2-D and 3-D measurement of cardiac function and anatomy, live 3-D imaging of the beating heart, and user-centered ergonomics. The iE33 system also offers high-performance features including voice-activated control and automated image optimization technologies. Philips said the iE33 is the first premium echocardiography system to feature fully integrated 2-D and 3-D cardiac quantification software for measurements such as left ventricle volume and ejection fraction, key indicators of heart health. The QLAB quantification software on the system uses 3-D border detection to provide rapid access to ventricular volumes of the whole heart and waveforms that show the function of 17 different segments of the heart simultaneously.

St. Jude Medical (St. Paul, Minnesota) reported the first European implant of its new SJM Tailor Annuloplasty Band for use in heart valve repair procedures. The implant was performed by Professor Hans-Joachim Schafers, MD, at the University of Saarland (Homburg/Saar, Germany), on a 57-year-old woman suffering from mitral valve endocarditis. Schafers said the patient is doing well and the device is performing as expected. The SJM Tailor Band, which was launched in the U.S. in July, is a flexible band that accommodates the natural movement of the mitral valve annulus. It can be used in both mitral and tricuspid heart valve repair procedures. The SJM Flexible Annuloplasty Delivery System allows easy implantation of the SJM Tailor Band with a one-step, push-button release. The handle quickly and securely attaches and detaches, while an extension handle offers an alternative for minimally invasive procedures. Malleable nitinol alloy sections of the holder and sizers are easily shaped, yet revert to their original form during heat sterilization.

Siemens Medical Solutions (Malvern, Pennsylvania) said its Angiography and X-ray Division has introduced Interventional Cardiac 3D (IC3D) technology to create 3-D images of the coronary vessels in the heart. When paired with an Axiom Artis imaging system from Siemens, IC3D allows cardiologists to view the coronaries in 3-D with as few as two images, leading to precision in determining appropriate stent size and length, faster examination times, the use of less contrast medium and lower radiation dosages.

Toshiba America Medical Systems (Tustin, California) reported the details of ongoing clinical research being conducted at Beth Israel Deaconess Medical Center (Boston) to further improve the clinical application of the company's Aquilion multi-detector computed tomography (CT) system. The Aquilion 16 CFX scanner has been installed and operational at Beth Israel Deaconess since January. Areas of research at the institution include thoracic, abdominal and cardiac CT clinical applications. Specific clinical research has addressed body angiography in applications such as pancreatic and liver transplant assessment, CT urography, interventional multi-slice fluoroscopy, and CT coronary arteriogram. Beth Israel also has performed clinical research to optimize imaging techniques using the Aquilion's isotopic imaging capabilities for non-invasive assessment of coronary artery diseases using CT angiography, as compared to cardiac catheterization. It also has improved CT colonography procedures and musculoskeletal applications on the hands to visualize tendons on patients with contraction deformities caused by trauma, burns or congenital defect.

Trimedyne (Irvine, California) said the U.S. Patent and Trademark Office has allowed its patent application on a new laser angioplasty device. The patent covers unique optical fiber devices designed to make smooth channels through plaque deposits in arteries, without radiating heat sideways, which could harm the vessel walls. The device is designed for use with small, portable, relatively inexpensive solid-state diode or Holmium lasers. The company said the new device can be made as small as 0.7 millimeters (1/30 inch) in diameter, allowing it to be used in arteries too small to admit current balloon angioplasty or stent delivery catheters. It also is designed to create a channel through fully blocked vessels, allowing balloon angioplasty or stent delivery catheters to be used.

Vascular Solutions (Minneapolis) reported that it has received FDA 510(k) clearance for the Langston dual lumen pigtail catheter. The two-lumen diagnostic catheter is indicated for use in the simultaneous measurement of pressures from two locations in the arterial system. The company said the Langston catheter offers simultaneous accuracy and precise responsiveness in measuring intra-arterial pressure gradients.

Welch Allyn (Skaneateles Falls, New York) reported the introduction of Smartlink Wireless, a rapid response system for transmitting critical patient data from an ambulance or helicopter to a receiving hospital's cardiac care team using a digital cellular network. The Smartlink Wireless system uses a Welch Allyn PIC 50 device that emergency medical services personnel (EMS) use to monitor, and if necessary defibrillate, a patient suffering from a heart attack. Once the EMS team has stabilized the patient for transport to a medical facility, they acquire and transmit a 12-lead electrocardiogram from the PIC 50 to a receiving hospital server using a handheld personal digital assistant (PDA). The receiving hospital server can then send the data to individual clinicians using web-enabled PDAs or telephones.

Zargis Medical (Princeton, New Jersey), a subsidiary of Speedus, said it has received FDA clearance to include a graphical display of the median energy level, timing and duration of suspected heart murmurs during specific segments of the diastolic and systolic intervals of heartbeats recorded through the Zargis Acoustic Cardioscan. The new displays will better represent the distribution of acoustic energy of the heart for each recorded location and help physicians characterize suspected murmurs in terms of onset, duration and loudness. The company said this clearance represents one of the planned development milestones required for a full commercial rollout of Cardioscan. Zargis will be demonstrating Cardioscan, with energy display and timing annotation, at the American Heart Association's annual scientific sessions in New Orleans this month.