The final battleground of the cardiovascular system: A major breakthrough in heart failure treatment technology
Heart failure, known as the "last battleground" in the cardiovascular field, is heating up.
Recently, more than a dozen companies, including Heyuan Medical, Hexin Medical, Tongxin Medical, and Corvia Medical, have successively completed financing. Multiple technological routes, such as cell therapy, ventricular assist devices, bionic pacemakers, atrial shunts, and heart failure monitoring, have achieved simultaneous breakthroughs.
The "Chinese Guidelines for the Diagnosis and Treatment of Heart Failure" point out that the prevalence of heart failure among adults in developed countries is 1% - 2%. However, data from the hypertension survey in China from 2012 to 2015 show that the prevalence rate among people over 35 years old has reached 1.3%, with a total of about 13.7 million patients, and the number is still rising, especially among those over 65 years old. What's more troublesome is that the existing first - line drugs can only delay the symptoms but cannot prevent the continuous deterioration of the disease. Although the in - hospital mortality rate has decreased with the standardization of diagnosis and treatment, the prevalence and mortality rates remain high, and the situation is still very severe.
When clinical needs intersect with innovative technologies, a real - sense treatment revolution is taking place.
Recent financing events in the heart failure field
01 Four major directions of innovation in heart failure treatment
The FDA's "Breakthrough Devices" list is often regarded as a vane of the intersection of clinical needs and technological innovation. Statistics from Arterial Network show that in the heart failure track alone, more than a dozen products have received this certification. This title is usually awarded to innovative medical devices with significant clinical potential, especially for serious or life - threatening diseases/conditions where there is a lack of effective therapies or existing therapies have major limitations. The fact that products in the heart failure field have densely received this title just confirms the urgent global clinical demand for innovative heart failure therapies.
Some companies in the heart failure field that have obtained FDA Breakthrough Device certification
Heart failure refers to the impairment of the heart's systolic and diastolic functions, which causes problems in the pumping function, resulting in the heart's output being insufficient to meet the metabolic needs of the body, and then presenting a series of symptoms and signs. Clinically, it is called heart failure.
According to the China Cardiovascular Doctor Innovation Club, currently, the innovative technological paths for heart failure treatment can be divided into four directions: ① Reduce the heart's load; ② Improve the heart's work efficiency; ③ Promote the repair and regeneration of the heart; ④ Prevent fluctuations in the heart's load.
In these four major directions, there are a variety of innovative products. They solve heart failure problems at different stages, and some phenomenal products have also emerged. For example, the left ventricular assist device (LVAD, artificial heart). Several domestic products have been approved for providing mechanical support for the blood circulation of patients with advanced refractory left - sided heart failure, that is, transitional treatment before heart transplantation or for restoring heart function, as well as long - term treatment. This product provides a treatment option other than heart transplantation for end - stage heart failure, and the number of implantations has increased rapidly after its launch. From 2017 to 2024, 187 hospitals across the country completed a total of 1,446 LVAD implantation surgeries.
Innovative technological paths for heart failure treatment. Source: CCI Cardiovascular Doctor Innovation Club
02 Cell therapy enters the confirmatory verification stage
Among various innovative directions, induced pluripotent stem cells (iPSCs) have the potential to make the heart "regenerate". iPSC technology reprograms human somatic cells into pluripotent stem cells and then differentiates them into cardiomyocytes with contractile function. These cardiomyocytes can integrate into the damaged myocardium, contract synchronously with the original cardiomyocytes, and work together to improve heart function, providing the possibility of curing end - stage heart failure.
This technological route has attracted the attention of large pharmaceutical companies at home and abroad. China Resources Sanjiu and Novo Nordisk have both laid out this cutting - edge technology through the joint development model. China Resources Sanjiu chose to cooperate with Elipus Regenerative Medicine and reached a joint development agreement on the latter's HiCM - 188 (iPSC cardiomyocyte) project. Novo Nordisk chose the Japanese company Heartseed and reached a joint development cooperation on the latter's pipeline HS - 005.
Wang Yong, the general manager of the R & D center of China Resources Sanjiu, said: "The heart is the power pump of the human body, and its regenerative ability is very limited after adulthood. Myocardial infarction leads to the loss of a large number of cardiomyocytes and the formation of fibrotic scars, which is the main cause of heart failure.
The existing drugs are more like giving an energy drink to a tired heart. Drugs like the "new quadruple therapy" can inhibit the excessive activation of the neuroendocrine system and reduce the heart's burden, but they cannot reverse the necrotic myocardium. Some existing interventional therapies, such as cardiac resynchronization therapy (CRT) or implantable cardioverter - defibrillator (ICD), can make the heart's contraction more coordinated and prevent sudden death, but they are just "auxiliary tools" and cannot repair the heart.
When heart failure reaches the end - stage, patients only have two options: waiting in line for a scarce donor heart or implanting a ventricular assist device. And iPSCs provide a third option: on the one hand, iPSC technology can directly supplement fresh cardiomyocytes; on the other hand, these cells can also activate the dormant cardiomyocytes in the patient's body through paracrine action, further promoting the repair and functional recovery of the myocardial tissue.
Although iPSC cardiomyocyte therapy for heart failure is full of prospects, there are also many challenges on the way to becoming a drug. At the production end, its complex production process places extremely high requirements on CMC (Chemistry, Manufacturing, and Controls). It is necessary to overcome stability problems such as cell viability, batch - to - batch differences, storage, and transportation, and at the same time, avoid potential safety risks such as tumorigenicity and heterogeneity. At the clinical application end, in - depth clinical exploration and research are needed: clarify the optimal population of indications, ensure the compatibility between the cell characteristics and the patient's cardiac electrophysiological characteristics (such as rhythm), explore the survival time, mechanism of action, and minimum effective dose of the cells in the body. The entire industrialization process requires in - depth multidisciplinary collaboration, forming a closed - loop feedback from process optimization to clinical protocol design, and gradually accumulating experience."
These challenges need to be solved by enterprises through long - term exploration. Currently, iPSC cardiomyocyte therapy has completed exploratory clinical trials and is entering the confirmatory clinical trial stage.
03 Two global companies are expected to take the lead in crossing the finish line
Elipus and Heartseed are leading the progress in iPSC cardiomyocyte therapy for heart failure. Both companies have made multiple breakthroughs in the field of iPSC cardiomyocyte therapy for heart failure.
Elipus' HiCM - 188 has launched a Phase II clinical trial in China. Currently, a multi - center, randomized, controlled Phase II clinical trial of human iPSC - derived cardiomyocyte therapy for severe heart failure has been officially launched in China, and subjects are being publicly recruited. It has also launched Phase I/II clinical trials in the United States, Singapore, Thailand and other regions. Elipus has completed clinical drug administration for 20 patients with heart failure using iPSC cardiomyocytes, with the number of cases ranking first in similar global studies. The earliest 2 subjects have more than 5 years of long - term follow - up data, and the results show the safety and encouraging expected efficacy of cardiac regeneration therapy. Elipus revealed that the significant research results of the Phase I clinical trial have been invited to be presented at the American Heart Association Scientific Sessions (AHA) to be held in November 2025, and the research data will be announced at that time.
When talking about the changes, the world's first subject, 60 - year - old Uncle Han, demonstrated a jog in place during a follow - up visit and said, "I couldn't even walk 50 meters before, but now I can run around a 400 - meter track with my grandson without getting out of breath. My heart is as strong as it was when I was young."
In terms of industrialization, Elipus has established an automated, standardized, and large - scale production line, which is the prerequisite for continuously and stably providing iPSC drugs. It has also greatly reduced the cost and improved the accessibility of future iPSC cardiomyocyte therapy for heart failure. This production line is also equipped with an AI - driven quality monitoring system to achieve batch - to - batch consistency.
The Japanese company Heartseed, which focuses on iPSC cardiomyocyte therapy for heart failure, originated from Keio University in Japan. Heartseed's technological features are its unique purification process and unique cell culture technology. It has established a simple method to achieve large - scale purification of cardiomyocytes, and it is highly reproducible. Novo Nordisk chose to cooperate with it precisely because of its purification technology.
In addition, Heartseed found that when transplanting single cardiomyocytes, the implantation rate of the transplanted cells in the heart is only a few percent. To solve this problem, by using the characteristic that the same type of cells adhere to each other through the extracellular matrix, it has created myocardial spheres composed of about 1,000 cardiomyocytes and a special transplantation device, which has increased the implantation rate of the transplanted cells by dozens of times.
Heartseed has two pipelines: HS - 001 and HS - 005. The difference between the two pipelines lies in the surgical approach. HS - 001 is administered through thoracotomy, while HS - 005 is administered through vascular intervention. HS - 001 is led by Heartseed in development, and the implantation of 10 high - dose patients has been completed. In the previous low - dose transplantation, significant improvement in clinical data was observed in 3 out of 4 patients. Therefore, Heartseed is optimistic about the better results of HS - 001 in the high - dose cohort. HS - 005 is jointly developed with Novo Nordisk, and clinical trials are planned to be launched from 2025 to 2027.
According to the schedules disclosed by the two companies, if everything goes smoothly, the first iPSC cardiomyocyte therapy is expected to be launched in 2028, and the regenerative medicine for heart failure is about to enter the commercialization window period.
04 The atrial shunt device acquired by Johnson & Johnson has become a hot spot for financing
Among the innovative technologies for heart failure, the atrial shunt device is also worthy of attention. The atrial shunt device (Inter - atrial Shunt Device, IASD) has been the most active in terms of financing in the heart failure device track in recent years: more than half of the global financing events in this field from 2023 to 2024 were concentrated in this segment.
The technological logic of the atrial shunt device is simple: through a vascular interventional procedure, a small channel is established between the left atrium and the right atrium of the heart, allowing blood to flow from the high - pressure left side to the low - pressure right side, thereby reducing the load on the left ventricle.
Corvia Medical atrial shunt device and implantation schematic diagram
A clinical doctor said: "Previously, when we performed transseptal puncture, we found that it would instantly reduce the patient's left atrial pressure and relieve the patient's heart failure symptoms. So, in fact, there has always been an atrial shunt procedure. As long as we artificially connect the left and right atria, we can relieve the heart failure symptoms, and this can relieve the symptoms for about 1 - 2 months. However, patients are limited by the fact that they cannot have surgery all the time, so there is a certain market for the atrial shunt device. But this is still a palliative therapy, a temporary solution that treats the symptoms but not the root cause."
The development of atrial shunt device products has been tortuous. The products have gone through multiple iterations, and no product has been approved by the FDA for marketing yet. In 2022, the REDUCE LAP - HF II study of Corvia Medical, a star company in the atrial shunt device field, showed that implanting the Corvia IASD in patients with heart failure with preserved ejection fraction (HFpEF) failed to reduce the composite endpoint events, which led to a sharp decline in industry confidence. The significance of this negative result is to suggest that IASD is not a "one - size - fits - all" solution, and the indications need to be more precisely stratified. In recent years, with the successive disclosure of positive results from new clinical data, the market sentiment has gradually recovered, and capital has flowed in again, driving product iteration.
An ideal atrial shunt device should be a "hexagonal warrior". It should ensure the safe and reliable operation of the device, with an extremely low surgical failure rate and complications; have sufficient radial support force at the waist to ensure a stable and continuous left - to - right shunt; have a precise and adjustable shunt aperture and flow rate; have as low a device - related thrombus incidence as possible, and a high long - term patency rate.
Currently, the first batch of atrial shunt device products has entered the late - stage clinical trials. In 2024, Johnson & Johnson acquired V - Wave for $600 million, marking the official entry of the giant into this field, and the commercialization process is expected to speed up.
The current clinical studies have provided a preliminary answer to the safety and effectiveness of the atrial shunt device, but there are still many questions that need further exploration. For example, how will the patient's baseline hemodynamic parameters affect the treatment effect of the atrial shunt? More clinical data are needed to consolidate this.
Overall, innovative heart failure therapies are moving from "symptomatic treatment" to "etiological intervention". Breakthroughs in emerging technologies such as cell and gene therapy, heart failure monitoring, and atrial shunt devices are reshaping the management paradigm of heart failure. In the future, multimodal combination, personalized precision, and commercial accessibility will become the core directions, and the ultimate goal is to achieve the vision of "preventable, controllable, and curable heart failure".
References
Renewed Hope - Interpretation of the Groundbreaking Relive - HF Study on Left Atrial Shunt in Heart Failure - CCI Cardiovascular Doctor Innovation Club
Special Spring Festival Edition | A Brief Discussion on the Essence of Heart Failure Treatment - Starting from the REDUCE LAP - HF II Study - CCI Cardiovascular Doctor Innovation Club
Atrial Septal Shunt Device for Heart Failure with Preserved Ejection Fraction: Chinese Experts' Understanding and Recommendations - Chinese Journal of Interventional Cardiology