AbiuroFatigue, shortness of breath, and chest pain may be symptoms of a disease known as aortic valve stenosis. It affects the heart and is characterized by an obstruction preventing the passage of blood from the left ventricle into the aorta and from there throughout the entire body. A frequent cause of this problem, which affects about 2% of people over the age of 65 and 3% over the age of 75, is an accumulation of calcium in the native valve that which obstructs the flow of blood. “The aortic valve has an orifice measuring 2.8 mm to 2.6 mm in diameter which, when stenotic, decreases to 0.7 mm or 0.5 mm, which can sometimes lead to sudden death,” says Dr. José Honório de Almeida Palma, a cardiovascular surgeon and professor at the Federal University of São Paulo (Unifesp) and the University of São Paulo (USP) Heart Institute (InCor). He coordinated the development of the new bioprosthesis from its initial tests on animals to the clinical phase involving implantation of the device, which repairs the natural mechanism for the passage of blood. Known as the Inovare Transcatheter Valve, it is manufactured by Braile Biomédica, based in São José do Rio Preto, São Paulo State. The product was developed by a group of researchers from the company, Unifesp, Universidade Estadual Paulista (Unesp), and InCor over a period of three years.
The solution is a first in Brazil and is going to make the product cheaper than similar devices imported from the United States, where two companies dominate the market and charge approximately R$120,000 per valve. The Brazilian valve sells at half the price or R$60,000. The outside of the transcatheter valve consists of a kind of stent, a small tube made of very fine wire mesh, which is placed inside arteries when there is narrowing or an interruption of blood flow. “The mesh is made of a cobalt-chrome alloy high in tensile strength and resistant to corrosion, with no sharp edges that could injure the inner lining of the blood vessels,” says Professor Antônio Carlos Guastaldi of Unesp’s Chemistry Institute Biomaterials Group, based in Araraquara, who coordinated the scientific aspect of the valve’s wire mesh development.
“The cutting and polishing of the valve’s wire mesh structure were done by the laser company Lasertools (see Pesquisa FAPESP Issue nº 173), located in São Paulo, so that the material would be perfectly smooth,” says Dr. Guilherme Agreli, a physician-physicist and director of the Braile Biomédica product. The company was established in 1983 by Professor Domingo Braile, who worked at USP, Unifesp and the State University of Campinas (Unicamp) and was one of the founders of the São José do Rio Preto School of Medicine (Famerp) (see the interview in Pesquisa FAPESP Issue nº 176).
abiuroPolyester fabric is sutured onto the inside of the stent “to prevent the passage of blood between the old valve and the implant,” says Guastaldi. The valve itself is placed inside the wire mesh tube. Made of bovine pericardium tissue, the membranal inner lining of a cow’s heart, it replaces the natural structure through which blood flows. “We have been using this biomaterial in other cardiac valves for many years. To obtain it, a Braile Biomédica team is able to collect the pericardia shortly after slaughter from cold storage facilities certified by the Ministry of Agriculture. After the material is treated with the appropriate solutions, it is processed and tanned, and then undergoes several tests before being used to make the valves. The whole process takes a month,” says Dr. Agreli. “The bovine pericardium is a biocompatible material, does not cause clotting and its mechanical properties make it suitable for use as a valve in the human heart,” he says.
The transcatheter valve has now been implanted in more than 300 patients in Brazil, and is especially suitable for elderly patients with medical limitations. Often they cannot withstand surgery that opens up the chest and implants a different type of valve in the same location. “In classic open heart surgery we stop the patient’s heart and do a bypass. Transcatheter valve placement can be done with minimally invasive surgery, with the heart and lungs functioning normally during the procedure,” says Dr. Palma. “We continue to use open-heart surgery, which is what we refer to as the gold standard, on younger patients but for the elderly with serious clinical conditions, the transcatheter implantation reduces the risk of death,” he says.
The procedure begins with a small incision on the left side of the chest or in the groin, next the catheter is guided through the arterial system until it reaches the apex of the heart and then the area where the bioprosthesis is to be implanted. Doctors monitor the surgery using x-rays and echocardiography, which show precisely where the valve is to be deployed. “To better monitor the image, the device has radiopaque markers that make the biovalve more visible on the x-rays and help to position it in the heart. The markers are made of tantalum, which is also a biocompatible metal,” says Guastaldi.
Within the catheter, the valve is compressed along with a small balloon. At the exact location, the device is placed on top of the natural aortic valve; no native tissue is removed. At this point the catheter makes the balloon inflate, thus opening the valve. When closed, its diameter measures between 6 mm and 7 mm. When open, it measures a maximum of 30 mm in diameter and is 2 centimeters (cm) high. After positioning the valve, the catheter and balloon are withdrawn, followed by the immediate restoration of circulation to the site. The incision made by the catheter at the apex of the heart is closed with stitches and heals quickly, according to the researchers.
Approved by the Brazilian Health Surveillance Agency (ANVISA) in 2011, information on the transcatheter valve implant procedure is being disseminated to Brazilian physicians. “I have traveled to a number of cities to teach the new technique,” says Dr. Palma, who received funding from FAPESP to test the device in pigs before implanting it in humans. “I’ve been to Rio de Janeiro, Porto Alegre and Goiânia, to perform the surgery while local doctors observed. They let me know when they have a patient who is ready for the valve, and I schedule the surgery,” he says. He and other Unifesp doctors, Dr. Ênio Buffolo and Dr. Diego Gaia, were involved in validating the valve with surgeons at USP’s InCor, the Hospital Beneficência Portuguesa in São Paulo, and Mercy Hospital in Porto Alegre.
Awards and investment
In addition to medical recognition, the valve won the 2013 Finep Innovation Award in the medium-size company category, an award given by the Brazilian Innovation Agency. It also received the 2012 Innovation Award from the Brazilian Medical Devices Manufacturers Association (Abimo). The Braile Biomédica valve has also been introduced by Unifesp’s group of researchers at medical conventions in England and the United States. “We began the partnership with Unifesp in 2004 and in 2007 we came up with the concept of aortic valve implantation via transcatheter; the partnerships also allowed us to incorporate new technologies such as Unesp’s biomaterials and Lasertools,” says Dr. Agreli.
Braile Biomédica invested about R$10 million in the project. “We were able to carry out a complex project involving different fields of knowledge. When we started in 2007 there were only two American companies that made aortic valves and now there are 30 companies in the world that are developing transcatheter heart valves; five of these are the same or very similar to our devices,” says Dr. Agreli. The company hopes to capture the Brazilian market by training medical teams, and then move on in search of foreign markets. The procedure performed to implant the new valve is not covered by the Unified Health System (SUS) of the Ministry of Health, but medical societies have taken initiatives to put the transcatheter valve on the list of procedures covered by the public system.
Professor Guastaldi of Unesp believes the project was a success because the various teams developed good relationships, with much understanding and competence, and the company also learned to relate well to university researchers. “We need to point out that heart surgery in Brazil today is on a par with that of other advanced nations, because we have companies like Braile Biomédica and researchers at universities that are open to developing new technologies and innovation,” Dr. Palma added.
Development of a transcatheter self-expandable aortic valve (nº 2011/15565-8); Grant Mechanism Regular Research Grant; Principal investigator José Honório Palma de Almeida da Fonseca – Unifesp; Investment R$ 54,450.15.