While much of the focus thus far in evaluating the connection between refractory migraines and patent foramen ovales (PFOs) has been concentrated on a few companies – including NMT Medical (Boston), AGA Medical (Golden Valley, Minnesota) and St. Jude Medical (St. Paul, Minnesota) – that are developing permanent implantable device technology to close the common heart defect, a few companies are quietly working on a minimally invasive treatment for the condition in which no device is left behind after the surgery. One player exploring this new no-device-left-behind approach for PFOs is privately held Cierra (Redwood City, California), via its PFx Closure System, which was conceptualized and initially funded by the well-known medical device incubator, The Foundry (also Redwood City), beginning in January 2003.

At the time of Cierra’s genesis, according to Erik Engelson, president and CEO, it was decided that the company initially would go for an approval in the refractory migraine market rather than the stroke market, which was what PFO closure devices were first designed to treat. “The Foundry identified PFO as an opportunity,” Engelson told Biomedical Business & Technology, and after looking at the stroke opportunity for PFOs, “decided that was a long clinical study and the two companies in that, NMT and AGA, had been having trouble enrolling patients.”

It was decided that migraine was a better business model for the company, especially since “some of the retrospective work in migraines looked very compelling.” Indeed, there are an estimated 2.2 million migraine sufferers with PFO and aura in the U.S., and retrospective studies have shown that closing a PFO can reduce migraine attacks. Of that number, an estimated 750,000 could possibly benefit from PFO closure, resulting in a market potential of nearly $3 billion in the U.S. alone.

The procedure, like those done by other players in the treatment of PFO that leave an implant behind, is performed by an interventional cardiologist in the catheterization lab. During the procedure, a guidewire is introduced via the right femoral vein to cross the PFO for balloon sizing and device placement. Next the company’s PFx catheter is advanced into the right atrium over the guidewire and once the device is in place, suction is introduced to tightly close the PFO and hold the PFO tissue against the inside of the device. Radio frequency energy then is applied to the suctioned area to “weld” the tissues of the PFO closed, with the entire procedure taking about 30 minutes to complete.

Not having an implant in the body after surgery presents several advantages, Engelson said. Some adverse events that he said are associated with implants include atrial fibrillation, which is reported in up to 12% of cases. Additionally, he noted that heart palpitations have been reported in up to 65% of patients and there also is the very real threat of thromboembolic issues.

Elsewhere in the product pipeline:

• The first U.S. multicenter, prospective clinical trial to investigate the use of minimally invasive stent placement to treat severe peripheral arterial disease (PAD) below the knee has been cleared by the FDA, with its approvals of an investigational device exemption filed by the study’s sponsors. The study, sponsored by Viva Physicians (VPI; Rosemont, Illinois) and supported by a restricted educational grant from the maker of the stent, Abbott Laboratories (Abbott Park, Illinois), will be the first in the U.S. to evaluate the Xpert expandable nitinol stent in the blood vessels below the knee. The Xpert already is cleared in the U.S. to treat blockages in the biliary ducts that carry digestive enzymes from the liver. VPI submitted its IDE application to study the stent’s use in the popliteal and tibial arteries below the knee to the FDA in February. The primary endpoint of the XCELL study is avoidance of major amputation at 12-month follow-up after treatment.

• Acusphere (Baltimore) reported the completion of enrollment in the second of its two Phase III clinical trials, RAMP-2 (Real-time Assessment of Myocardial Perfusion-2), for the company’s lead product candidate, AI-700. AI-700 is an investigational ultrasound contrast agent designed to assess myocardial perfusion. Currently there is no approved ultrasound contrast agent to assess blood flow to the heart muscle. The company said it anticipates making a public announcement regarding the RAMP-2 trial results in 4Q06. Separately, the company reported results for the RAMP-1 clinical trial and an intellectual property license with GE Healthcare (Waukesha, Wisconsin). The company’s trials of AI-700 are designed to demonstrate that stress echo with AI-700 is non-inferior to nuclear stress testing in the detection of coronary heart disease.

• Biophan Technologies (Rochester, New York) reported that the U.S. Patent and Trademark Office recently issued the company two new patents. The patents are for methods of signaling the heart, which improve the function of implanted cardiovascular devices. The first, U.S. patent No. 7,020,517, teaches a means of detecting and responding in a manner that avoids the onset of ventricular fibrillation. The method uses a low voltage electrical signal, which can be built into a low cost pacemaker and provide some protection against fibrillation events. The technology can also be deployed in a cardio-defibrillator as a means of controlling fibrillation to avoid the need for the 800-volt charge traditionally used in implantable defibrillators. The second patent, U.S. patent No. 7,054,686, teaches use of a high-frequency pulse sequ-ence in place of a single pacing signal so that stimulation of the heart can occur with lower energy, a technique with the potential to improve battery life of implantable devices.

• Biotronik (Lake Oswego, Oregon) said it received “approvable” status from the FDA for the Kronos LV-T Cardiac Resynchronization Therapy Defibrillator (CRT-D) and Corox OTW Coronary Sinus lead, which complete Biotronik’s pioneering Heart Failure Therapy System. The Kronos LV-T is a CRT defibrillator offering a wireless heart failure monitor for continuous tracking and monitoring of the status of heart failure patients. Six proven variables are automatically tracked and trended daily. Through Home Monitoring, the Kronos automatically transmits intracardiac electrograms via radio frequency communications and allows the physician to view this vital patient information on a secure web site. The Corox OTW coronary sinus lead offers low acute and chronic thresholds averaging below 1 V. The Progressive Curve configuration of the Corox OTW means the lead coils distinctively at the tip, with a more relaxed curvature further from the apex, when the guide wire or stylet is removed. The primary advantage of this configuration is secure fixation in a wide range of vein diameters. The second key attribute is that the electrode is positioned against the wall of the vessel, which Biotronik said leads to lower acute and chronic LV thresholds than competitors’ CS leads.

• Boston Scientific (Natick, Massachusetts) said that results of a clinical trial designed to study unnecessary pacing in recipients of an implantable cardioverter defibrillator (ICD) were presented at the Heart Rhythm Society meeting in Boston. The trial, INTRINSIC RV (Inhibition of Unnecessary Right Ventricular Pacing with AV Search Hysteresis in ICDs), was designed to advance the company’s understanding of a proprietary feature that minimizes unnecessary right ventricular pacing in patients who received the company’s market-released dual-chamber ICD. INTRINSIC RV is a multicenter, randomized trial enrolling more than 1,500 patients in the U.S., Germany, Italy and Australia. Nine hundred eighty-eight patients with mild and moderate pacing requirements were randomized to either atrial support pacing or ventricular only pacing groups. The trial used Boston Scientific’s AV Search Hysteresis feature, which has been incorporated in all the company’s dual-chamber ICDs since June 2000. Separately, Boston Scientific reported that it has received FDA clearance to launch its Sterling Monorail and Over-the-Wire Balloon Dilatation Catheter in the U.S. The balloon catheters are available in a broad range of sizes. Both balloon catheter platforms are engineered for use in the renal and lower extremity arteries, as well as in dialysis fistula. In addition, the Sterling Monorail Catheter received a specific indication for use in the carotid arteries as both a pre- and post-dilatation balloon. The Sterling Balloon Dilatation Catheter features an ultra-low profile balloon (4 Fr), designed to meet the challenges of the peripheral vasculature. Its refined profile is complemented by a balanced shaft featuring seamless transitions, which the company said is designed to offer clinicians enhanced trackability and powerful push when faced with traversing challenging anatomy.

• CardioDynamics (San Diego), a provider of impedance cardiography (ICG) technology, reported publication of the company’s PREDICT (Prospective Evaluation and Identification of Decompensation by ICG Test) study, demonstrating a significant relationship between BioZ ICG parameters and the occurrence of near-term major heart failure events. The results were published online in the Journal of the American College of Cardiology and also in the June print version of the journal. “The PREDICT results suggest that when performed at regular intervals in stable patients with heart failure with a recent episode of clinical decompensation, ICG can identify patients at increased near-term risk of recurrent decompensation,” said Milton Packer, MD, of the University of Texas Southwestern Medical Center (Dallas), principal investigator of the study and lead author on the paper.

• Concentric Medical (Mountain View, California) and the SITS Network (Stockholm, Sweden) reported their partnership on the THRUST (Throm-bectomy in Unsuccessful Stroke Thrombolysis) study, to be sponsored by Concentric Medical and managed by the SITS Network. The study is anticipated to begin enrolling patients later this year, and will investigate the Merci Retrieval procedure in ischemic stroke patients who fail standard thrombolytic therapy. THRUST will compare the clinical outcome of patients treated with mechanical thrombectomy using the Merci Retrieval System vs. patients with no further intervention. Concentric Medical is focused on developing new stroke treatments, while the objective of the SITS Network is the broad implementation and amplification of evidence-based stroke treatments.

• DiaDexus (South San Francisco, California) said that the U.S. Patent and Trademark Office issued U.S. patent No. 7,052,862, covering methods of diagnosing a patient’s susceptibility for developing an atherosclerotic disease, including myocardial infarction and stroke, by analyzing a sample of a patient’s blood for the presence and activity of Lipoprotein Associated Phospholipase A2 (Lp-PLA2). Lp-PLA2, an enzyme associated with atherosclerotic plaque, was discovered by scientists at GlaxoSmithKline (GSK; London). This patent is one of several GSK patents to which diaDexus has an exclusive commercial diagnostic license. diaDexus sells the PLAC test, an Lp-PLA2 mass-based test for use as an aid in assessing patient risk of stroke or heart attack. diaDexus and GSK are developing an activity-based test for diagnostic purposes.

• Digirad (Poway, California), a provider of cardiovascular imaging services and solid-state nuclear medicine imaging products, reported the release of the new Cardius 3 XPO triple-head cardiac gamma camera at the Society of Nuclear Medicine meeting in San Diego. The Cardius 3 XPO imaging system introduces Solidium high-definition solid-state digital detector technology, a new design that allows imaging of patients weighing up to 500 pounds and offers up to 38% faster image acquisition times than conventional dual-head systems. The company said the Cardius 3 XPO delivers more patient comfort, enhanced clarity of diagnostic results, achieving greater imaging speed and producing images of superb quality.

• Endologix (Irvine, California), which manufactures minimally invasive treatments for vascular diseases, reported receipt of FDA approval to begin marketing its next-generation Visiflex Delivery System for use with the Powerlink System for the minimally invasive treatment of abdominal aortic aneurysm. The company said it plans to introduce the Visiflex in the U.S. market through a controlled launch program to further develop targeted physician feedback and to build inventory, with full commercialization anticipated this fall. The Visiflex is designed to provide im-proved catheter flexibility for delivery of the Powerlink endoluminal stent graft device. An integrated radiopaque band marker on the outer sheath and molded component parts are expected to enhance catheter visibility and facilitate smoother withdrawal in difficult anatomies.

• Estech (San Ramon, California) reported the market launch of AFfirm, an atrial fibrillation (AF) conduction block verification probe. AFfirm assesses the effectiveness of cardiac ablation treatments, which create new electrical paths in the heart, resulting in improved cure rates. The pacing probe’s flexible design allows easy access to treatment sites, including minimally invasive or stand alone treatments for AF.

• GE Healthcare (Waukesha, Wisconsin) said it showcased its updated Vivid cardiovascular ultrasound platform at the recent American Society of Echocardiography meeting in Baltimore. The Vivid 7 Dimension ’06, a PC-based, software, raw data ultrasound platform, is designed to help clinicians assess cardiovascular anatomy and left ventricular function with more accuracy by making 4-D cardiovascular imaging easier to use during clinical exams. The Vivid 7 features multi-dimensional imaging formats, real-time, ungated, unspliced 4-D imaging and real-time 4-D full-volume imaging in an easy to use package. New quantitative analysis tools include advanced tissue synchronization imaging and automated function imaging.

• MedicalCV (Inver Grove Heights, Minnesota) reported that it has submitted a 510(k) application to the FDA seeking clearance for its Atrilaze minimally invasive system for the potential treatment of atrial fibrillation (AF) in a closed-chest, beating-heart setting. The submission marks a key point in the company’s transition from a previous focus on heart valve therapy via ablation. The Atrilaze is a laser-based system designed to enable access to and ablation of cardiac tissue including AF, an erratic heartbeat and is the most commonly occurring cardiac arrhythmia. AF alters normal cardiac function, is a major precursor to congestive heart failure and is associated with an increased incidence of stroke. According to a company statement, there currently are four primary treatments for AF utilizing drugs, implantable devices, catheter-based treatments and open-chest surgery. The company said it believes its Atrilaze system will allow surgeons to complete an ablation procedure that will produce lesions that closely mimic those obtained by using the classic Maze surgical procedure, which is the current standard of care.

• Medwave (Danvers, Massachusetts), maker of sensor-based, noninvasive blood pressure measuring solutions, reported that it has submitted a 510(k) application to the FDA for its Fusion noninvasive Patient Monitor System with Vital Signs Options. Fusion offers Medwave’s sensor-based blood pressure solution, while also incorporating pulse oximetry from Nellcor (Pleasanton, California) and thermometry from Kendall (Mansfield, Massachusetts). Fusion can be configured from a stand-alone blood pressure device into a complete vital signs monitor. According to the company, it is the first noninvasive blood pressure and vital signs monitor that is purely sensor-based.

• PLC Systems (Franklin, Massachusetts), a provider of cardiac laser technologies, said that a review of new cardiac tissue regeneration research was presented at the annual meeting of the Asian Society for Cardiovascular Surgery in Osaka, Japan. Focused on the intramyocardial application of bone marrow-derived stem cells in combination with CO2 transmyocardial revascularization (TMR), the presentation included data on stem cell therapy alone, stem cells with coronary artery bypass graph (CABG) surgery, and stem cells combined with CO2 TMR. The researchers concluded that stem cells combined with CO2 TMR provide an increased improvement in cardiac function in heart failure patients when compared to stem cells alone or stem cells with CABG. The company introduced its CO2 TMR Heart Laser technology at the meeting, which it said is the first TMR angina relief device approved by both the Japanese Ministry of Health, Labor and Welfare and the FDA.

• Polymer Technology Systems (PTS; Indianapolis) is launching globally what it called “the world’s first direct low-density lipoprotein (LDL) cholesterol test” for use at the point of care, riding a trend toward healthcare self-management, which increasingly means self-monitoring. While the product is ultimately planned to be offered over the counter (OTC), currently it is CLIA-waived, FDA-approved and reimbursed by the Centers for Medicare & Medicaid Services (CMS; Baltimore) for use by physicians, pharmacies and other healthcare providers. It must still go through FDA approvals before being offered OTC. “The LDL [number] is the ‘Holy Grail’ of lipid testing, and that’s simply because it is the bad cholesterol,” CEO Robert Huffstodt said. “That’s why [physicians] are going to put you on a statin drug, and until our technology was available, there was nothing at point of care that would give you a direct reading.”

• Roche Diagnostics (Indianapolis) reported that its newest coagulation monitoring system, the CoaguChek XS system for physician’s office use, has been submitted to the FDA for 510(k) clearance. The CoaguChek XS system is a small, hand-held, easy-to-use instrument for prothrombin time/ INR testing. It provides fast results –in about a minute – and requires only one drop of blood from the fingertip. The test strip was designed with built-in controls, which it reads to determine strip integrity. The strips can be dosed on the top, right or left side, making it easier for patients to apply blood. The CoaguChek XS system gives information about a patient’s level of anticoagulation directly on the spot and allows their healthcare professional to adjust, if necessary, the doses of medication to a level that reduces the risk of major complications.

• Stereotaxis (St. Louis) reported the completion of a proof-of-concept demonstration of a magnetically enabled endocardial injection catheter developed in collaboration with the Biologics Delivery Systems Group of Cordis (Miami Lakes, Florida). The procedure, performed by Emerson Perin, MD, of the Texas Heart Institute, St. Luke’s Hospital (Houston), in-volved the remote magnetic steering of the Stereotaxis Niobe Magnetic Navigation System, the electromechanical mapping features of the Noga XP Cardiac Navigation System and a uniquely designed, magnetically enabled injection catheter. Performing the entire procedure remotely from the control room, Perin mapped the left ventricle and identified and easily navigated the magnetic injection catheter to 15 targeted injection sites in the left ventricle. He was able to obtain excellent injection delivery, including delivery to the most challenging ventricular locations.

• St. Jude Medical (St. Paul, Minnesota) reported FDA approval of its newest devices for treating pati-ents with heart arrhythmias and heart failure. The Epic II ICD (implantable cardioverter defibrillator) and the Epic II HF CRT-D (cardiac resynchronization therapy defibrillator) devices feature enhanced telemetry speed for faster device communications and a “patient notifier” that gently vibrates to alert patients of critical changes in device function. The Epic II devices also include SenseAbility technology to optimize sensing parameters that may protect against inappropriate ICD shocks.