Author: Zhang Jing

Source: China Food and Drug Administration

 Intracardiac ultrasound (ICE) is an emerging echocardiographic diagnostic technology, which places a catheter equipped with a micro-ultrasound transducer probe inside the cardiac chambers through a vascular pathway, transmits and receives high-frequency ultrasound signals, and realizes real-time imaging of cardiac anatomy. Currently, ICE has been applied to a variety of procedures, such as radiofrequency ablation of atrial fibrillation, left auricle occlusion, atrial septal defect occlusion, mitral valvuloplasty, endomyocardial biopsy, and so on.

 Clinical studies have shown that the application of ICE can effectively improve the accuracy, safety and efficiency of atrial fibrillation radiofrequency ablation, left heart ear blockade and other surgical procedures, reduce the risk of surgery, minimize complications, shrink the cost of surgery, and at the same time improve the comfort of patients. Based on the significant clinical advantages, the market demand for ICE system is very broad, and many well-known multinational companies around the world are actively laying out ICE-related product pipelines.

 Technology Iteration and Upgrade

 As early as the 1950s, some researchers began to explore the use of catheters and ultrasound technology to image the heart structure. However, due to technical limitations, the exploration was not successful. It was not until the 1980s that ICE was applied with the development of ultrasound imaging and catheterization. However, at the beginning of its application, ICE's high transducer frequency (20-40 MHz) and limited tissue penetration capability could not be used to obtain intracardiac anatomical maps.

 Since then, some researchers have developed low-frequency transducers (9 MHz) that allow ICE systems to image intracardiac structures, but these systems still suffer from shortcomings such as low catheter flexibility, low imaging depth, and inability to be used to observe intact cardiac structures. In response, some R&D manufacturers have optimized the imaging depth of ICE systems by using lower frequency (5MHz) transducers, but the corresponding transducer size is large, limiting the clinical application of ICE products.

 With the innovation and advancement of ultrasound phased array technology, ICE has ushered in an opportunity for development. The application of ultrasound phased array technology in the field of ICE not only solves the problem of large transducer size, but also promotes the further expansion of the clinical applications of ICE systems. Simply put, phased array ICE has greater imaging depth and clearer images. At the same time, ICE can also provide a variety of imaging information, such as color blood flow signals, tissue Doppler images, spectral Doppler images, and so on.

 At the same time, the ultrasound transducer has been miniaturized, promoting the widespread clinical application of rotary ICE. Rotary ICE and phased-array ICE have their own advantages: rotary ICE provides higher near-field resolution in applications, and phased-array ICE provides a variety of information such as cardiac anatomical structures, color blood flow signals, and spectral Doppler images. Currently, phased array ICE is more widely used and dominates the market.

 At the turn of the century, Siemens Healthcare introduced the first 2D ICE catheter, ACUSONAcuNav. This product was initially used to guide atrial septal puncture, and subsequently began to be used in a variety of structural heart surgery procedures, such as atrial septal defect occlusion, and left auricle occlusion. 2D ICE supports biplane or triplane imaging, which displays two or three different planar views, but the physician needs to reconstruct these images in his or her mind into a 3D anatomical structure.

 With the wide application of ICE, its performance has been optimized, and it has gradually evolved from two-dimensional imaging to three-dimensional imaging, which greatly enhances the guidance and visualization capabilities. Three-dimensional ICE can directly present three-dimensional anatomical structure diagrams during application, which facilitates doctors to carry out surgery more easily.

 In recent years, Siemens, Johnson & Johnson and other companies have innovated and launched real-time 3D ICE systems. Compared with 2D ICE, real-time 3D ICE is not only capable of real-time imaging, but also can display the three-dimensional structure of the heart and blood flow and other information, and present a clearer and more accurate image.

 From the direction of product development, it is expected that more and more ICE systems will be developed from 2D to 3D, and even from 3D to 3D real-time imaging, which will develop in the direction of greater clarity, precision and multi-functionality.

 Clinical advantages are obvious

 Previously, there have been clinical applications of transesophageal ultrasound (TEE) and transthoracic ultrasound (TTE). Compared with TEE, ICE is more flexible and can image from inside the heart, thus more accurately detecting blood clots and guiding surgery. In addition, TEE requires general anesthesia for some special populations, while ICE only requires local anesthesia and avoids the discomfort of esophageal intubation, as well as the mechanical damage to the esophageal wall mucosa from the TEE probe and the thermal damage that can be caused by scanning. Compared with TTE, ICE is not affected by obesity, emphysema, thoracic deformity and other factors, and can realize shorter distance and higher precision imaging.

 At the same time, compared with TEE, TTE and other traditional methods, ICE can real-time monitoring of intraoperative thrombosis and pericardial effusion and other potential risks of complications, thus effectively improving the safety of the operation; at the same time, ICE can be operated independently by the doctor, does not rely on ultrasound and anesthesiologists, the surgical arrangements are more flexible, but also reduces the cost of the operation personnel to improve the efficiency of the operation, reducing the operation of the various aspects of the time-consuming.

 In clinical practice, TEE results have been the gold standard for detecting left atrial and left auricular thrombus before performing atrial fibrillation catheter ablation or left auricular blockade. Of interest, there are clinical data showing that the accuracy of ICE and TEE in the assessment of left auricular thrombus is comparable, and the image quality of ICE is higher; while ICE is superior to TEE in terms of the validity of the diagnosis of left auricular thrombus.

 In addition, by scanning the catheter layer by layer from one end of the left auricle to the other, ICE can completely display the maximum caliber, diameter of the landing zone, and effective working depth of the left auricle in each axial direction, thus guiding the selection of the blocker more precisely. A multicenter study found that ICE-guided left auricular occlusion was less time-consuming and more efficient in all aspects of the procedure, with a significant reduction in the cost of anesthesia and ultrasound professionals.

 In the treatment of atrial fibrillation, ICE has been used early on for catheter ablation of atrial fibrillation. Compared with traditional X-ray imaging, ICE can effectively reduce the amount of X-rays used, reduce radiation exposure to patients and physicians, and can be used to more clearly and accurately determine the cardiac condition during the procedure. Therefore, ICE can replace or partially replace X-ray imaging technology in the field of AF treatment.

 Based on the advantages of ICE's high surgical precision, low safety risks, and fewer patient complications, shorter hospitalization time, and faster recovery, it is expected that the technology will be applied to a wider range of clinical applications.

 Huge market space

 In terms of application scenarios, ICE has high clinical application value in the treatment of atrial fibrillation, congenital heart disease, cardiac stroke, atrial septal defect, mitral stenosis, tricuspid stenosis, aortic stenosis and other diseases. The domestic patient population of the above diseases is extremely large, and with the steady rise in the income level of the population and the increasing demand for accurate treatment, ICE products are gradually developing into just-demand products.

 The strong market demand breeds a huge market. Arterial network in accordance with the ICE catheter market price of 20,000 yuan / root, the market penetration rate of 10% for the calculation, China's ICE catheter market size of more than 10 billion yuan; in accordance with the ICE host market price of 1 million / unit for the calculation, if each three hospitals are equipped with only one ICE host, China's ICE host market size of more than 1.4 billion yuan (does not include the non-triple A hospitals).

 Although the ICE market has broad prospects for development, it is still in the early stages of development. China Structural Heart Disease Industry Report 2021” released by the Structural Heart Disease Group of the Cardiovascular Physicians Branch of the Chinese Medical Doctors' Association in January this year shows that in 2021, the volume of transcatheter aortic valve replacement surgeries (excluding clinical studies) in China exceeded 6,500, the volume of transcatheter rim-to-rim repair surgeries is about 350, the volume of left heart ear block surgeries is about 14,000, and the volume of congenital heart disease interventional The volume of surgery is about 75,000 cases, and the number of structural heart disease interventions in China is far from reaching a plateau.

 It is noteworthy that more and more innovative medical devices for structural heart disease treatment, such as transcatheter mitral valve repair devices, transcatheter tricuspid annuloplasty devices, and trans-femoral vein tricuspid valve repair devices, have been approved by domestic innovative enterprises one after another. Meanwhile, relevant enterprises are increasing the market education and academic promotion of ICE technology and products. Against this background, the penetration rate of structural heart disease interventional procedures in China will continue to increase, and the use of ICE products for structural heart disease interventional procedures will further increase.

 Data released by Frost & Sullivan shows that the market size of China's structural heart disease interventional devices market has grown from 400 million yuan in 2017 to 2 billion yuan in 2021, with a compound annual growth rate of 48.3%; it is expected that by 2025, the market size will reach 10.4 billion yuan, with a compound annual growth rate of 51%. It is foreseeable that the size of the ICE market will also grow at a high rate in tandem.

 Enterprises actively layout

 At present, a number of global medical device giants, such as Siemens, Philips, GE Healthcare, Johnson & Johnson, Abbott, Boston Scientific, etc. have laid out ICE field. Among them, Siemens, Johnson & Johnson, Philips and other companies have developed 3D or 4D imaging ICE products, some of which have been approved by the U.S. Food and Drug Administration (FDA) for marketing. In China, the ICE products that have been approved for marketing are mainly from multinational companies such as Siemens, Boston Scientific, Johnson & Johnson, and Abbott.

 It is noteworthy that many innovative enterprises in China, such as TingSheng Technology, Saihe Medical, Ice Crystal Intelligence, Xinhuan Technology, etc., are also actively developing ICE products and have made breakthrough progress. For example, Ting Sheng Technology has successively developed 2D and 4D imaging ICE systems, the former is mainly used for simple structural heart disease and electrophysiology surgery, while the latter is mainly used for complex structural heart disease and electrophysiology surgery. The former is mainly used for simple structural heart disease and electrophysiology surgeries, while the latter is mainly used for complex structural heart disease and electrophysiology surgeries. In March this year, Nicholson Technology completed the first exploratory human clinical trial of domestically produced ICE.

 The ICE system independently developed by Saiho Medical successfully completed domestic animal experiments in August this year, and the experimental results show that the product has good safety and image function effectiveness. At present, the product has formally entered the clinical trial stage.

 Ice Crystal Intelligence completed a 10 million yuan angel round of financing in August this year, and the funds raised will be mainly used for the company's HD-ICE (next-generation cardiac intracavitary ultrasound) product research and development. The product has high definition and high maneuverability, and is expected to further improve the effectiveness and safety of structural heart disease interventional procedures.

 In addition, Heartworld's ICE system is also in the R&D stage.

For the above innovative enterprises, on the one hand, as China's ICE market is still in the early stage of development, the related products and market penetration rate is relatively low, the enterprises have a large space for development; on the other hand, many well-known medical device enterprises around the world are actively laying out the field of ICE, which will bring great competitive pressure to the innovative enterprises. In this case, local ICE enterprises should increase the investment of personnel, equipment, environment, capital and time, focus on the development and optimization of transducer process, connecting cable process and encapsulation process, improve the production efficiency and yield rate, ensure the realization of mass production, and at the same time, reduce the manufacturing cost as much as possible, so as to further improve the competitiveness of the enterprise itself.