Pioneering China's First Transcatheter Mitral Valve Repair Device: Crossing the Dark River Toward Light

"Is it difficult to develop transcatheter mitral valve (TMV) devices? Yes, it is. If it's so difficult, why do we still pursue it? Because patients are waiting, and the industry is waiting. Faced with this revolutionary innovative technology, if the team over-considers pros and cons, this initiative might ultimately fail. As technical R&D personnel, we must believe that after crossing the dark river, the light is ahead."

The time goes back to July 2015.

The European Society of Cardiology (ESC) released a statement on surgical and interventional treatments for mitral regurgitation, recommending the use of interventional treatments for mitral regurgitation that have already matured abroad in clinical practice.

Around the same period, mitral regurgitation interventional repair devices developed by U.S.-based companies such as MitraClip and Edwards successfully passed clinical trials and were gradually launched in local markets, with a surgical success rate exceeding 93%.

In the same year, the number of patients with mitral regurgitation in China reached nearly 9.6 million. According to a Frost & Sullivan report, this figure exceeds one-tenth of the total global patient population for that year, while the number of transcatheter mitral regurgitation treatment devices available in China was zero.

Not only that, among the 9.6 million patients, the number of cases of patients who have the conditions and ability to receive MitraClip implantation treatment is less than a hundred. Patients without such conditions can only consider medication and traditional surgical treatment. Moreover, due to surgical risks, a large number of moderate to severe patients even give up receiving traditional surgical treatment. They live under the shadow of potentially developing secondary heart failure or even sudden death at any time.

But this situation does not arise because domestic medical technology is incapable, nor because Chinese doctors lack competence. Rather, it is due to the lack of innovative devices in the market that can truly address clinical pain points.

"Patients in China are waiting, and the industry is waiting."

As one of the founders of Valgen Medtech, Zhang Tingchao deeply understands the pain points of the lack of innovative solutions in clinical practice and the difficult situation of patients.

Choosing to open up a wilderness never before trodden by predecessors inevitably involves a lonely journey.

In 2013, the foreign frontrunner in the same track, MitraClip, was launched in the United States; the following year, the MitraClip Asia-Pacific Registry (MARS) study included 163 cases of secondary mitral regurgitation from five Asia-Pacific regions.

When foreign medical devices advance into the interventional treatment era for mitral regurgitation, related research in China is still in the exploratory stage.

From 2012 to 2014, there were only 3 successful MitraClip implant surgeries in Shanghai and 10 in Hangzhou. Compared with the increasing number of patients each year, the nearly half of high-risk surgical patients, and the 57% mortality rate of critically ill patients within the year, the total volume of surgeries as the "gold standard" leaves one feeling powerless.

"So many Chinese patients are still enduring pain while waiting, life is equal and priceless, someone should do something for them."

In 2015, Zhang Tingchao and the Valgen Medtech team stepped forward, determined to cultivate a path in the previously "barren" field of mitral valve interventional treatment in China.

Zhang Tingchao recalled that when the team initially decided to develop interventional treatment devices for mitral valve, some members had doubts and hesitations about this direction. On one hand, there were many participants in the overseas market, with various technical solutions under development, but more clinical evidence was still needed to prove the safety, efficacy, and market value of these solutions. On the other hand, the field was characterized by high technical barriers, and domestically, the landscape appeared almost deserted.

However, Zhang Tingchao firmly believes that in the face of uncertainty, persistence and effort will surely bring rewards. The Valgen Medtech team must be courageous in exploring and making breakthroughs.

In the early stages of exploration, Valgen Medtech faced quite challenging technical problems. Due to the highly complex anatomy of the mitral valve (including the annulus, leaflets, chordae tendineae, papillary muscles, etc.), the varied pathology and anatomy of mitral regurgitation, as well as the influence of atrial and ventricular function and size on the mitral valve, among other factors, the design of interventional treatments for the mitral valve must consider the highly mobile leaflets, complex chordae tendineae, three-dimensional structure of the annulus, and more. The design of the delivery system via the femoral vein route faces the challenge of the longest and most curved pathway, while post-implantation fatigue durability also presents significant difficulties and rigorous tests in the design process.

Even in 2014, a year of "hundred schools of thought contending" in the international medical field of mitral valve treatment, major medical device giants such as MitraClip, Edwards, and Intrepid invested heavily in large-scale clinical research, yet they still struggled to significantly improve the stability of various TMVs.

At that time, internationally, only three products had received CE approval: Mitraclip's edge-to-edge clip, Carllion annuloplasty, and Neochord artificial chordae. The FDA had only approved some uses of Mitraclip. It was not until 2020 that MitraClip was approved by China's drug regulatory authority for domestic marketing in China.

As global medical device R&D enters a bottleneck period and China adopts a cautious approach to technology introduction, Valgen Medtech has transformed these challenges into fertile ground for corporate growth. It is within this environment that "Made in China" is quietly brewing a resilient force to address the significant challenges of mitral valve interventional technology.

"If the direction is wrong, the return may be years of futile effort. But I have always believed in this direction. I have always said that the team should not stay in the balance of pros and cons, whether it succeeds or not, we will know only after doing it." Zhang Tingchao said.

However, the transcatheter mitral valve (TMV) intervention device is like a vast ocean. First, there are not many directions and solutions to draw on both domestically and overseas. Second, the anatomical structure of the mitral valve is complex, requiring products to have extremely high standards in structural design as well as precision and stability during operation. Third, clinically applicable solutions have yet to be explored, leaving immense room for practitioners to "think outside the box." How can one find the right path amidst all this?

To this end, Valgen Medtech has invested substantial resources and efforts in exploring solutions.

This includes extensively reviewing literature in the early stages, studying the principles and effects of mitral valve treatment. Visiting various departments such as cardiology, cardiac surgery, and ultrasound departments both domestically and internationally, and discussing with clinicians the technical direction, technical principles of mitral valve treatment, as well as the challenges faced in clinical mitral valve treatment.

For example, at that time, the main treatment methods for patients with mitral regurgitation in China were conservative drug therapy or surgical procedures. For instance, most organic lesions were caused by chordae tendineae rupture, yet a major surgery was required to replace a suture as an artificial chordae for the patient. In 2014, 40% of patients in Chinese mitral valve wards had organic lesions; another example is functional mitral regurgitation, where patients had extremely poor physical function and could not undergo surgical treatment. So, which design solution could be feasible given the technological level and surgical imaging environment at that time?

Zhang Tingchao knows that as a technology developer, one must deeply understand cutting-edge technologies, international technological trends and changes, and the clinical effects such technologies can bring, in order to find a direction truly suited for the company’s development positioning—doing the right things and doing things right.

Countless days and nights, countless inquiries and visits, Valgen Medtech finally dared to anchor on the direction of "artificial tendons" and began truly in-depth exploration and research.

In 2016, Valgen Medtech experienced its first setback, with experiments failing continuously 7 or 8 times. As Zhang Tingchao put it, they were like a boat navigating the sandy sea, struggling immensely.

Fortunately, a meeting changed this situation. Zhang Tingchao approached his mentor, Academician Zhang Xingdong, and discussed the difficulties currently faced by the Valgen Medtech team. After listening, Zhang Xingdong smiled and said, "You feel disheartened after failing seven or eight times? You should be embarrassed! If you want to innovate and succeed, how could it be so easy?"

Later, Zhang Xingdong told Zhang Tingchao that he had insisted on the research of cartilage regeneration technology 20 years ago, and this research direction was questioned by many people in the early days. But it was precisely because he insisted on the direction he chose at that time that he was able to prove the correctness of this research direction more than ten years later.

"The opposite of success is not failure, but the sedimentation and accumulation of experience. Encountering difficulties in the research and development process is inevitable, and as a developer, one must learn to accept this inevitability with equanimity," said Zhang Tingchao.

In a letter, he wrote to the team: "In innovation and R&D, failure is commonplace. If one cannot accept failure or is easily defeated, they are not suited for R&D. I have always believed that only through experiencing failure can we learn which paths are impassable, and ultimately find the right way forward. As long as every step is taken with full dedication, they will accumulate into the most valuable asset, helping you discover the methods and pathways to success."

Ultimately, during the four years that the Valgen Medtech team ventured into the mitral valve treatment field, they developed China’s first clinically applied transcatheter mitral valve repair product for transapical access — the MitralStitch® Mitral Valve Repair System. This is the world's first product capable of both artificial chordae tendineae repair and edge-to-edge repair, and also the first to complete two mainstream mitral valve repair procedures.

For him, this is a breakthrough in global TMV, the first proof of the correctness of Valgen Medtech's research direction over the years, a true reflection of the product's value and significance, and an indication that the company can continue to develop positively and achieve greater value.

"That day, I finally had a good night's sleep," said Zhang Tingchao.

The long-term technical accumulation and phased achievements have brought development confidence to Valgen Medtech. However, faced with the scarcity of mitral valve repair devices in China and the diverse needs of patients with different conditions, Valgen Medtech has once again set its goals, strengthened its confidence, and continued to move forward. MitralStitch is a transapical product, and compared to internationally mainstream products, the trauma from a transapical approach tends to be relatively greater. China should also have its own minimally invasive mitral valve repair device via the femoral vein.

In 2020, Valgen Medtech made another breakthrough by collaborating with the Second Affiliated Hospital of Zhejiang University School of Medicine and the National Engineering Research Center for Biomaterials at Sichuan University to develop China's first transvenous mitral valve edge-to-edge repair device – the DragonFly® Mitral Valve Clip System, which has become the fastest progressing product in China and is about to be commercialized.

Back in the first half of 2020, the outbreak of the pandemic made the overall progress of Valgen Medtech slow and difficult.

At the onset of the pandemic, it was just before the human clinical application of DragonFly®. The product needed to undergo factory batch verification, laboratory testing, animal experiment evaluation, and third-party agency testing to verify its effectiveness, reliability, and quality consistency. To ensure the product could smoothly enter the human clinical application phase within the expected timeframe, it was essential to proceed with the animal experiments.

"That period became the time with the most overtime and all-nighters for the team."

As Zhang Tingchao recalled, the team members at that time prioritized their work over themselves, taking risks without hesitation and rushing to various locations to conduct animal experiments while carrying heavy boxes. One team member, upon learning that his residential community was about to be locked down, immediately ran home, grabbed a quilt, and returned to the company’s conference room. He pushed the meeting table aside and slept on it until dawn, then woke up to continue working. He lived in the company for two whole weeks just to push forward the product's progress. Especially during the first half of 2020, at the peak of the pandemic when fear was at its highest, every member of the team refused to give up and did everything they could to keep things moving forward.

"The sense of mission to bring glory to domestic devices drives us to act in this way, and the bond among team members is our driving force. Valgen Medtech's entire team has come a long way. We have weathered difficulties together and celebrated successes together. We don’t want to stop, nor do we want anyone to be left behind. We have agreed to work hard together and then harvest abundant fruits together. As pioneers of domestic technology and R&D, we can feel the mission and responsibility on our shoulders," the team members said.

It is these efforts that enabled Valgen Medtech to successfully complete its goal according to the original plan. On July 23, 2020, the team led by Wang Jian'an from the Second Affiliated Hospital of Zhejiang University School of Medicine successfully completed the world's first clinical application of DragonFly® in humans.

In 2015, 2016, 2017…, Zhang Tingchao remembers every step Valgen Medtech has taken very clearly. Whether it was the team overcoming challenges in 2017, the product "breaking through its cocoon to become a butterfly" in 2019, or facing the pandemic at this critical moment in 2020, the ups and downs of these experiences remain vivid for Zhang Tingchao as if they happened just yesterday.

Fortunately, the team eventually lived up to expectations, relying on an indomitable spirit, becoming stronger through challenges, and demonstrating a deep understanding of the hardships of innovation and the importance of learning from failure. Time and again, they rose from setbacks, summarizing lessons and standing firm.

For those who dare to venture into the TMV track, perhaps not all perseverance will lead to a qualitative change. But there are always some efforts that can make flowers bloom in this rarely-trodden wilderness. And that, is enough.

In the future, Valgen Medtech will continue to shoulder its mission and responsibility, base itself in China, explore more paths for the development and advancement of China's medical devices, and strive to become a leader in the global valve field.