Published: October 28, 2015; Source: Forbes Chinese
In June 2013, at the reception of 25th Anniversary of the First Rotary LVAD Invention Conference, Dr. Chen Chen, the founder of CH Biomedical, a company specializing in LVAD development, met 68-year-old Joe Ann Bivins who received LVAD implantation, because Ms Bivins developed severe heart failure in 2005, it was so critical, she was near to death.
Fortunately, doctors at the University of Michigan in the United States were able to perform a VAD implantation on him. In the next several years, Mr. Bivins found a new lease of life and said his life was almost as normal as anybody else. The rotary axial flow LVAD, made by the Thoratec Corporation, the world's largest LVAD company, had been working in Mr. Bivins's body for nearly eight years by the meeting with Dr. Chen. Mr. Bivins died at the beginning of last year, he had set the world record for the longest extended life span relying on a single LVAD. "Every time I see a patient like this, I am greatly encouraged." Dr. Chen said.
This sophisticated smart device that looks nothing like a human heart, is a ventricular assist device the size of a flattened golf ball that can replace the heart’s function. It is the equivalent of a tiny, high-powered blood pump that is attached to the apex of the patient’s heart and replaces the pumping function of the human heart by creating a new bypass that allows blood to bypass to reduce the burden of the weakened heart. "The heart is the most important organ of our body, because it has a single function without any requirement of complex chemical material exchanges, it is probably one of the easiest organs to be replaced with an artificial organ." Dr. Chen said.
Heart disease is the second leading cause of death worldwide. Heart failure is the progressive condition of the heart after suffering severe damages. There are more than 20 million heart failure patients worldwide, more than 7 million deaths caused by heart failure each year. Over 1 million patients with critical heart failure require heart transplants.
However, transplanting a living heart from someone else is not only extremely expensive, difficult, and risky, but also limited by a shortage of heart donors. Even in the United States where the largest number of heart transplants were performed, just over 2,000 heart transplant surgeries were performed in 2014, and a little above 200 in China. It explains why the market for VAD is still in its early stage with great prospect of fast growing largely.
Scientists have been doing research on “LVADs” since the 1950s. “If it weren't for President Kennedy’s project to land on the moon, LVADs would probably be applied to patients extensively by now." Chen said jokingly. The idea of the LVAD came from the application of Cardiopulmonary resuscitation machine (CPR) used in open chest surgery. If it is made small enough, it is an LVAD.
The first generation of LVADs mimicked the contractions of the human heart to make the blood circulate, they were bulky as large as a traditional military water bottle. When implanted, they had to be squeezed into abdominal cavity and connected by long grafts through the diaphragm to the heart and aorta in the chest cavity. But even so, it has created many miracles in saving lives. "You can't imagine the pain of an advanced heart failure patient, they were very happy to have the bulky device, they can even go snow skiing with an LVAD." Dr. Chen said.
In the 1970s, inspired by industrial pumps, Dr. Wampler introduced rotary pumps to LVADs (VAD). This creative idea greatly reduced the size of the LVAD (VAD), the pump could be placed directly into the human chest cavity. It was a huge leap forward in the development of the LVAD, based on this achievement, Thoratec made the long-lasting HeartMate II, creating many miracles. "It's like the invention of the airplane, pioneers tried to imitate birds, hoping to take off by flapping their wings, after many failures, they finally figured out that the lifting force generated by speed was the only way to get the airplane to take off". Dr. Chen said.
Chen, 52 years old, who was born in Nanjing, Jiangsu province, wanted to study medicine when he was young. However, because he was found to have weak color vision during a physical examination, he was restricted from studying medicine and had to choose the thermodynamics major at Tsinghua University. After graduation, Chen did not give up the hope of switching to a medical-related major. He was admitted to Chengdu University of Science and Technology (later merged with Sichuan University) to pursue a master's degree in biomechanics.
However, Chen soon realized that biomechanics, which studies how blood flows through blood vessels, was not his ideal major: "We often worked on arm-drawn theories, even the questions for study were all made up, and the results were just for publication." After obtained his PhD degree, Chen worked in Nanjing University of Science and Technology as a professor.
In the 1990s, Chen was sent to Japan as a visiting scholar at the University of Tokyo. The visit gave Chen his first exposure to an artificial heart. Chen joined Professor Hiroshi Inai’s lab at the University of Tokyo, who was one of Japan's leading artificial heart researchers. Professor Hiroshi worked on a total artificial heart, a completely mechanical device to replace a patient's weakened heart.
However, a total artificial heart can only be used as a short-term solution for patients waiting for transplant, and most heart failure patients have no need to replace their hearts. "I felt that such a transitional product would eventually become obsoleted and have no commercial future, so I decided to give it up on this study direction." Dr. Chen said. After leaving the University of Tokyo, he transferred to another university in Japan to start a new major – research on magnetic levitation bearings.
In 1999, when Chen was changing majors and uncertain about his future, Brad Paden, a professor at the University of California, at Santa Barbara, approached him and invited him to join his own start-up company to develop a maglev VAD. In contrast to the total artificial heart being studied by the Japanese professor, almost all the artificial hearts being commercialized in the United States were ventricular assist devices designed to be implanted in the body for a long time.
"In patients with advanced heart failure, most of their heart muscle is damaged, but there is still a considerable amount of muscle that can work". A great number of cases proved that VAD can help the damaged heart muscle to get recovered by giving them time to “relax”, so they are likely to be “regenerated” Dr. Chen explained.
Chen decided to join the American start-up company not only because Chen focused on the prospect of commercial applications of the LVAD in the United States, at that time, the first generation of LVAD had been approved by FDA and available on market, the second generation of rotary VAD invented by Dr. Wampler had also appeared, also Dr. Chen believed the exploration of magnetic levitation LVAD was the direction of the new generation of technology.
Although the second generation of rotary axial flow VAD is a substantial leap forward compared with the first generation of LVAD, it increased the risk of thrombosis.
On the one hand, some blood cells damaged by bearings might induce thrombosis, On the other hand, second-generation VAD recipients must take long-term anticoagulants to prevent blood clotting, which may cause patients bleeding. "Many second-generation VAD recipients’ hearts were cured but died from stroke or other complications." Dr. Chen explained. "Full Maglev technology allows the VAD bearingless, to avoid crushing the blood cells, therefore, the risk of blood clot was reduced dramatically. Dr. Chen explained.
After three years of research and development, the start-up company that Chen joined, in 2002, unveiled Levacor, a full magnetically levitated VAD with satisfactory results in animal studies. Clinical trials on human would cost a lot of money, the founders had no desire to continue running a company that no longer required much technological innovation, so the company was sold to the Nasdaq-listed WorldHeart Corporation, which was still selling first-generation LVADs. Chen joined the WorldHeart company in 2005 as the chief engineer.
Taking part in the process of starting a business had a huge impact on Chen. "I found that even a small startup company can make the best product with advanced technology in the world." Chen Chen said.
After acquired Levacor, WorldHeart thought their product could go straight from the first generation of VAD to the third, but it did not go as smoothly as it was expected. In 2006, WorldHeart brought Levacor™ into the clinical trial. That is when Chen realized that the Levacor's design had a fatal flaw – because of its large size, the maglev pump had to be placed in the abdomen cavity. Meanwhile, the rival HeartWare International Inc. released a hydrodynamic floating VAD, said that can solve thrombosis issue, and is small enough to be placed directly in the chest. "For doctors, the complexity of the procedure is the key factor to be decided which product to use." Chen said.
However, the management of WorldHeart, which had already invested heavily in Levacor™, did not want to face this major design mistake and still hoped to promote Levacor™. The company was eventually mired in bankruptcy and acquired by HeartWare in 2012.
Chen hoped to build a maglev VAD that could be placed directly into the chest, but he knew WorldHeart would not make the decision to redesign it. In 2007, Chen resigned and returned to China. The next year after his return, he founded CH Biomedical in Suzhou. His goal was to make maglev VAD as small as possible. It was a race against one of the world's leading companies – Thoratec which had more than 30 years of experience on developing LVAD, had turned its sights to the development of a maglev VAD.
With a market value of more than $3 billion, Thoratec is currently the world leader in the VAD industry, with revenue of about $480 million in 2014, far ahead of HeartWare, the No. 2 company with revenue of about $280 million. In addition, Thoratec was the only public company in the LVAD section that remains profitable.
To date, Thoratec has provided VADs for more than 20,000 patients with advanced heart failure, and HeartMate II, the second-generation LVAD, continues to dominate the market. In 2012, Thoratec launched HeartMate 3, a full-magnetic levitation VAD, which has entered clinical trials.
In August 2015, the FDA released a statistical report showing that HeartWare’s Fluid Dynamic Bearing VAD did not improve the incidence rate of blood clots or stroke rates compared with HeartMate II. On the other hand, Thoratec's HeartMate 3 clinical trial has shown good clinical results, further confirming that the magnetic levitation VAD will be a trend in the development of LVAD technology.
In 2011, Chen created a magnetic levitation LVAD called the CH-VAD that was small enough to fit in human chest. "It was really exciting. We were already doing animal experiments." Chen recalled. But Chen paused when he discovered that Thoratec had also developed HeartMate 3.
When Chen heard that Thoratec’s maglev VAD was smaller than his own, he was reminded of the Levacor’s design mistake. A team of consultants at CH Biomedical USA had a heated debate about whether they should stop animal testing of the previous product and continue developing a smaller maglev heart. Almost all the team members thought it was impossible to go smaller, but Chen decided to push the limit by minimizing the device. In 2013, Chen Chen came to the Thoratec booth with his newly developed CH-VAD in his pocket, and he was relieved to see his magnetic levitation device was smaller than HeartMate 3. "Sooner or later, we're going to beat the current leader in the market." Chen Chen said confidently. In pursuing "smaller," Chen has also scaled back the number of wires that connect VAD to an external power source from 10 to four, while Thoratec’s HeartMate 3 has six wires. "Don't underestimate this innovation," he said. "A broken wire can cause the VAD stop working, and the fewer wires, the more reliable the VAD is." As a result, CH Biomedical has applied for an international patent for protection, Chen noted.
Another reason for Chen's confidence is the cost of the product. The high price is the direct reason why VADs are not applied widely at present. In the United States, a VAD system sells for an average of $100,000, for total cost of implantation, including VAD, surgery, and patient management can cost $200,000 – a threshold that is out of reach for most patients with advanced heart failure.
"We can effortlessly reduce the price of VAD to half of what it is now or even lower," Chen asserted, "This is an advantage that Chinese companies can play in R&D and manufacturing, and we can use China's advantage in cost to influence the development of the global LVAD market in turn."
Due to barriers such as technology and cost, LVAD is still up for grabs in the Chinese market, and international manufacturers have been unable to enter China due to difficulties in follow-up services and other problems. CH Biomedical has been conducting animal studies in both China and the United States. "Based on the results, the trials are satisfactory and are expected to enter a clinical trial after completion of the animal studies in the first half of next year." Chen said.
However, because LVAD has not yet been developed in China, to conduct a clinical trial in China, the submission for IDE and the process of the approval could be a huge challenge. Currently, Chen is preparing to conduct clinical trials in the United States and China simultaneously, also he is actively seeking strategic investors. "As long as the product goes to market, it doesn't matter who controls the company in the future." Chen said.