Reclaiming the Forgotten Tricuspid Valve: Chinese Physicians' Dedication and Innovation in Transcatheter Therapies

The human heart beats approximately 2.5 to 3 billion times over a lifetime, accompanied by the ceaseless opening and closing of the heart valves.

According to incomplete statistics, there are at least 30 million patients with valvular heart disease in China. As the aging of China’s population intensifies, the prevalence of valvular heart disease continues to rise, with an incidence rate exceeding 6.4% among individuals aged 65 and older. More critically, valvular heart disease significantly alters intracardiac hemodynamics, leading to cardiac enlargement, heart failure, and arrhythmias, resulting in extremely high rates of mortality and disability.

Among these, tricuspid regurgitation, a serious yet often overlooked disease of the right heart system, frequently occurs secondary to left-sided valvular diseases and atrial fibrillation. Due to its insidious onset, initial clinical symptoms are often neglected, and historically, there have been no ideal treatment options available; thus, it has been referred to as the "forgotten valve."

Amid the global advancement of transcatheter interventions for aortic and mitral valves, transcatheter tricuspid valve intervention has begun to break new ground, with preliminary research findings instilling hope among interventional cardiologists in this field.

Today, in the field of tricuspid valve therapy, known as “the final piece of the cardiovascular puzzle,” a group of Chinese doctors has remained steadfastly committed, while a cohort of Chinese enterprises continues to innovate, achieving R&D progress that even surpasses that of multinational corporations on a global scale. It is this group’s exploration of interventional therapies for valvular heart disease that has ushered in the fourth revolution in interventional cardiology.

Tricuspid valve pathology rarely occurs in isolation and is frequently associated with other cardiac conditions. This disease is not only insidious in onset and presents significant intraoperative challenges, but also poses substantial difficulties in the development of effective therapies, leading to its historical neglect. It was not until the late 1980s that the severe consequences of tricuspid valve disease began to receive proper clinical attention.

However, it is precisely this neglect that delays diagnosis and treatment, causing patients to miss the optimal window for intervention. The number of patients with tricuspid valve disease is continuing to rise.

The global number of patients with tricuspid regurgitation (TR) increased from 46.6 million in 2016 to 50.6 million in 2020, and is projected to reach 60.7 million by 2030. In China, the number of patients with tricuspid regurgitation rose from 8.6 million in 2016 to 9.2 million in 2020, and is expected to increase to 10.6 million by 2030.

Moreover, severe tricuspid regurgitation can lead to reduced cardiac output and systemic congestion, which may impair patients’ quality of life in mild cases and result in mortality in severe cases.

Regarding treatment modalities, surgical intervention still suffers from drawbacks such as significant invasiveness, a high incidence of complications, and elevated mortality rates. More than half of patients are ineligible for surgical treatment due to factors including advanced age, impaired cardiac function, and severe comorbidities.

Data indicate that the outcomes of surgical treatment for tricuspid regurgitation are suboptimal. The perioperative mortality rate for isolated surgical tricuspid valve replacement is as high as 10.9%, while that for isolated surgical tricuspid valve repair is 8.1%. These figures are several times higher than the perioperative mortality rates for isolated surgical mitral valve repair (1.4%–2.6%), mitral valve replacement (3.8%), and aortic valve replacement (2.2%).

The ultimate consequence of this situation is that a large number of patients with severe tricuspid regurgitation are left with only conservative management via conventional pharmacotherapy. Although medical therapy has demonstrated clear efficacy in managing right heart failure, it is largely unable to reverse the progression of the condition and has been proven to provide only transient benefits. Notably, the one-year mortality rate for patients with severe tricuspid insufficiency receiving medical management alone is as high as 36.1%, indicating a grim prognosis.

Fortunately, transcatheter tricuspid valve intervention (TTVI) has brought hope to patients with tricuspid regurgitation.

The 2021 ESC/EACTS Guidelines for the management of valvular heart disease recommend considering transcatheter tricuspid valve intervention in patients with symptomatic severe tricuspid regurgitation who are at high surgical risk and have suitable anatomical conditions.

China started in this field basically at the same time as the international community, and even took the lead. With the promotion of the development of this field by the industry, academia, research, and medical circles, more and more Chinese doctors have joined hands with domestic innovative medical device enterprises to explore this field.

Tricuspid valve treatment strategies are diverse, varying according to patient anatomy, etiology, and disease progression. Currently, transcatheter tricuspid valve devices independently developed in China include the NeoBlazar® transcatheter edge-to-edge repair system, the LUX-Valve system, and the K-Clip™ transcatheter tricuspid annuloplasty system.

Professor Lu Fanglin of the Department of Cardiovascular Surgery at Changhai Hospital, affiliated with Naval Medical University, is the principal inventor of the LuX-Valve, a transcatheter tricuspid valve replacement device. The first “non-radial force-dependent” transcatheter tricuspid valve device has completed enrollment of 150 patients in its confirmatory clinical trial. Meanwhile, the K-Clip™ transcatheter tricuspid annuloplasty system has officially launched its confirmatory clinical trial following the successful inaugural implantation by Academician Ge Junbo from Zhongshan Hospital, Fudan University, together with experts including Professor Zhou Daxin and Professor Pan Wenzhi.

Edge-to-edge repair, as the only interventional technique globally to have undergone large-scale, long-term clinical validation confirming its safety and efficacy, has already made significant strides in the field of mitral valve treatment. Recently, the TRILUMINATE Pivotal study, prominently announced at the American College of Cardiology Annual Scientific Session and World Congress of Cardiology (ACC.23/WCC), has added robust evidence supporting the safety and efficacy of transcatheter edge-to-edge repair (TEER) for the tricuspid valve. Results from this prospective randomized controlled trial demonstrated that, during one-year follow-up, the TEER group achieved significantly greater improvements in tricuspid regurgitation and quality of life compared to the control group, with an extremely low incidence of major adverse events post-procedure. These findings fully highlight the clinical benefits of TEER technology for symptomatic patients with severe tricuspid regurgitation.

In China, the primary hub for innovation and exploration in transcatheter edge-to-edge tricuspid valve repair (TEER) originated in Xiamen, which witnessed the birth of the NeoBlazar® transcatheter edge-to-edge tricuspid valve repair system. To date, under the guidance of Xiamen University Affiliated Cardiovascular Hospital, this product has been used in over 50 tricuspid valve procedures. There were no perioperative deaths among the subjects; immediate postoperative regurgitation was significantly reduced, and clinical symptoms showed substantial improvement during follow-up.

Xiamen University Affiliated Cardiovascular Hospital (hereinafter referred to as “Xiamen Heart Center”), as a sub-center of the National Clinical Research Center for Cardiovascular Diseases, performed the first case of ventricular aneurysm plication outside Europe and has since become the center with the highest global volume of such procedures. It was the first in the Asia-Pacific region to complete the transapical implantation of the AMEND mitral annuloplasty ring. The hospital routinely performs various complex and challenging transcatheter valve interventions, accumulating extensive and comprehensive surgical experience in the minimally invasive treatment of valvular heart disease, and initiated early exploration into transcatheter tricuspid valve interventions.

Wang Yan, President of Xiamen Cardiovascular Hospital, regards this as the final frontier in the field of structural heart disease. He believes that, in the absence of existing solutions, physicians have an obligation to offer hope to both the medical community and patients. He is determined to overcome the formidable challenge of tricuspid valve disease—a condition characterized by a high patient burden and severe complications, yet one that has long left clinicians with few effective options.

The tricuspid valve features a larger annulus and valve area compared to the mitral valve, exhibits significant anatomical variability, possesses more fragile annular tissue, and has thinner leaflets and chordae tendineae. Due to this complex anatomical structure, traditional valve stent design concepts are hardly applicable to the clinical anatomical and physiological needs of patients with tricuspid regurgitation, posing substantial challenges to the design and application of surgical devices.

After extensive research and clinical practice, Wang Yan believes that, drawing on the developmental trajectory of aortic and mitral valve surgeries, transcatheter edge-to-edge repair (TEER) will gradually become the mainstream interventional approach for tricuspid regurgitation. To this end, Wang Yan collaborated with Zhenyi Medical to jointly develop the NeoBlazar® Transcatheter Tricuspid Edge-to-Edge Repair System.

In July 2022, Wang Yan’s team successfully performed a minimally invasive transcatheter tricuspid valve repair using the NeoBlazar® transcatheter edge-to-edge tricuspid valve repair system in a high-risk patient with severe functional tricuspid regurgitation. This case marked the first enrollment in the NeoBlazar® confirmatory clinical trial across China, officially launching the nationwide multicenter clinical study.

Recalling the first surgery, Wang Yan admitted that due to differing understandings of the surgical plan and concepts, the entire procedure took nearly seven hours. His inner anxiety was only alleviated at the moment the surgery succeeded and the patient regained consciousness. Since then, he has identified the right direction and developed more precise surgical techniques.

As the first tricuspid valve repair device in China to enter large-scale clinical trials, and the only product at this stage capable of delivering two valves through a single sheath, the NeoBlazar® transcatheter edge-to-edge tricuspid valve repair system has seen rapid patient enrollment and numerous breakthroughs. Dr. Wang Yan and his team, working jointly with corporate engineers, continuously refined the protocol during research and clinical trials.

Currently, nearly 120 hospitals in China have performed edge-to-edge mitral valve repair procedures, whereas only a handful are capable of conducting edge-to-edge tricuspid valve repair. The primary challenges lie in the complex anatomical structure of the tricuspid valve and the intricate pathophysiological mechanisms of tricuspid regurgitation, which impose higher demands on transesophageal echocardiography (TEE). In particular, for patients who have undergone surgical valve replacement in the left heart system—whether with mechanical or bioprosthetic valves—severe artifacts are generated during conventional TEE assessment, posing significant difficulties in the evaluation of the tricuspid valve.

Wang Yan, in collaboration with the Xiamen Cardiovascular Hospital echocardiography team, innovatively applied a multi-view transesophageal approach combined with intraoperative multi-angle 3D transthoracic echocardiography analysis. This technique avoids artifacts from surgical valves, enables effective valve assessment, significantly improves the efficiency of preoperative evaluation, and reduces operative time, thereby pioneering transcatheter edge-to-edge tricuspid valve repair procedures in China.

Compared to the 5–6 hours required for a single procedure in the past, the NeoBlazar® transcatheter edge-to-edge tricuspid valve repair system reduces the operative time to under 2 hours. Relative to existing products on the market, this undoubtedly further enhances the safety and efficacy of the procedure.

“In the field of cardiac surgery, errors may occur during innovative exploration, but they should be avoided no matter how minor. ‘Do no harm’ is a fundamental principle I have always adhered to, and any technological innovation should be built upon this philosophy,” said Wang Yan.

Behind the impressive achievements lie the clinical experience, wisdom, and dedication of physicians and engineers. Due to the unique anatomical location and structure of the tricuspid valve, the development path of NeoBlazar® has been fraught with thorns and challenges.

It is precisely for this reason that Wang Yan permits virtually no errors in device R&D. He remains uncompromising, even as clinical trials approach. Before initiating clinical studies, Wang Yan requires the team to provide more than 10 product units, from which he randomly selects several for extreme stress testing. Clinical trials may only commence if all tested units pass; otherwise, the process must be restarted from scratch. This rigorous standard reflects not only his demands on engineers but also his commitment to safeguarding patients’ lives.

Wang Yan stated, “As physicians, we hope our products are life-saving. Therefore, we have subjected the product to rigorous scrutiny, raising one seemingly insurmountable and stringent requirement after another—from the clamping force and weight of the clip applier to the catheter models and device stability—and then working together to overcome them one by one. After dozens of iterations and optimizations, the product performance has reached an excellent level, yet we still demanded improved steerability. This is because ‘better steerability’ means that more patients can gain access to surgical intervention, saving more lives, and allowing us physicians to operate with greater ease and confidence during procedures.”

The NeoBlazar® transcatheter edge-to-edge tricuspid valve repair system operates on a mechanism similar to that of the TriClip system approved in Europe and the United States. However, Zhenyi Medical has drawn upon extensive frontline clinical experience from Xiamen Cardiovascular Hospital, implementing significant innovations and optimizations in product design. These enhancements ensure that the device’s design and performance are better aligned with the disease characteristics of Chinese patients and the procedural preferences of Chinese physicians.

Currently, NeoBlazar® features the smallest controlled bending radius among domestic products, establishing itself as a high-quality Chinese-made device whose performance surpasses that of international competitors. Among more than 50 completed cases, patients included those at high risk for redo sternotomy, such as individuals with severe tricuspid valve prolapse, prior corrective surgery for tetralogy of Fallot (trilogy), post-repair of ventricular/atrial septal defects, post-permanent pacemaker implantation, and multiple left-sided valve replacements (aortic/mitral valves). NeoBlazar® has provided these patients with a novel therapeutic option.

“We had a patient with severe tricuspid regurgitation, graded DTR 5+ preoperatively. Having sought medical advice across multiple regions due to intolerance to traditional open-heart surgery, the patient found hope in an innovative, domestically developed device. Postoperatively, the regurgitation was reduced directly to 1+. This represents the greatest significance of China’s medical innovation.”

“With patients’ lives repeatedly resting in his hands, Wang Yan is acutely aware that there is virtually no room for error.”

Since Edwards Lifesciences’ Cardioband received European approval in 2018, the tricuspid valve is no longer the “forgotten valve.” Currently, three devices have obtained CE certification in the European Union.

Although no transcatheter tricuspid valve intervention products have been approved in China, hospitals, research institutions, and companies such as Zhenyi Medical have conducted continuous research in the field of heart valves over the past five years, achieving substantial and breakthrough progress in the development and clinical application of valvular interventional devices.

Currently, research on devices and treatment modalities for tricuspid valve disease is advancing rapidly, with an increasing number of manufacturers focusing on interventional approaches and device design. In the future, open-heart surgeries will gradually become less frequent, as new minimally invasive interventional techniques are increasingly adopted.

It is worth noting that before the market truly achieves significant scale, Chinese physicians must remain committed to advancing and ultimately realizing numerous research explorations. Whether it is the empowerment of healthcare-related industries through technological progress or the extension of benefits to a broader patient population via emerging achievements, the development of domestically produced innovative medical devices provides ample reason for optimism. The collaborative explorations by medical experts such as Ge Junbo, Lu Fanglin, and Wang Yan, along with academia and industry, will serve as sparks igniting this “previously uncharted” frontier.

When the “forgotten valve” is no longer forgotten, we are well aware that in the exploration of life’s boundaries, humanity will never halt its progress due to the thorns along the way.