Big country Great Medic｜Nianguo Dong's team, pioneer of heart transplantation in China

On May 31st, under the concerted treatment of a multidisciplinary team led by Professor Nianguo Dong, Director of the Department of Cardiovascular Surgery at Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology (hereinafter referred to as "Wuhan Union Hospital"), a 9-month-old baby, Hanhan, successfully received a heart transplant. This is an operation that has attracted the attention of billions of people. A fresh heart flew from Guangxi to Wuhan, starting a relay of life spanning more than 1,000 kilometers. Professor Nianguo Dong's team brought Hanhan a new life, bringing the first Children's Day of her life.At present, Wuhan Union Hospital has established a complete set of heart transplantation technology system suitable for national conditions.

Professor Dong Nianguo's team in surgery

In the field of cardiovascular surgery in China, Professor Nianguo Dong's team from Wuhan Union Hospital are the leading experts. Not only can they perform all cardiac surgical procedures but are also one of the few teams in China that performs more than 100 heart transplant operations per year. The team has continuously made breakthroughs in R&D of several key technologies, making outstanding contributions to the development of heart transplantation.

Top 3 in the world: They have continuously held it for 7 years

Heart transplantation is the ultimate solution to save the lives of patients with end-stage heart disease, especially those with severe heart failure. In China, the incidence of heart failure is 0.9%. There are about 4 million heart failure patients nationwide, of which severe patients account for about 7% to 10%. Professor Nianguo Dong tells us that the patients with severe heart failure have a relatively high mortality rate. At present, heart transplantation is the most effective treatment method, and there are very few alternatives.

"My first patient was on September 26, 2008, a 20-year-old boy. Due to congestive hepatopathy at that time, he was completely unable to eat when he was brought in, and his abdominal was in severe pain.”Professor Nianguo Dong still clearly remembers this patient. After a successful heart transplant, this patient lived for more than a decade.  

Since the first heart transplant in 2008, Professor Nianguo Dong's team has continued to develop heart transplantation technology. In the past 7 years, the annual number of heart transplant operations has been around 100, maintaining the top three in the world. The five-year survival rate for patients after surgery is 84% which is 11% points higher than the International Society for Heart and Lung Transplantation report. The ten-year survival rate is 65%, which is 7-8% points higher than the international one.

In terms of quantity and quality, Prof. Dong and his team have achieved something extraordinary. So, in terms of technology, what major breakthroughs have they achieved?

Professor Nianguo Dong told us that in improving the effect of heart transplantation, they have mainly made breakthroughs in the following aspects to improve the effectiveness of the heart transplantations:

First, is to establish the donor heart preservation strategy of Wuhan Union Medical College Hospital. In the field of heart transplantation, due to the shortage of donor hearts, in many cases, the donor heart will be collected from other places. In this case, how to prolong the cooling time of the donor hearts and strengthen the protection of the myocardium is particularly important. The international standard for donor heart preservation is 4 hours. Wuhan Union Hospital has developed a special transfer box, which obtained 3 national patents, which can effectively prevent the donor organ from overcooling and overheating. This extends the preservation time of the donated heart to 6-8 hours, greatly improving the use efficiency of the heart.

Second, is to overcome a series of technical difficulties in complex heart transplantation,including heart transplantation with aortic malformation, one-stop hybrid heart transplantation, combined heart multi-organ transplantation, right-sided heart transplantation, etc.

Third, important breakthroughs have been made in children's heart transplantation. Currently, in pediatric heart transplantation, Wuhan Union Hospital has performed more than 100 surgeries. It ranks first in the country, accounting for more than one-third of the country's total and has also set several national records in children's heart transplants. For example, the two youngest heart transplant cases in the country completed last year, one was a three-month-old infant of 4.3 kg, and the other was a 66-day-old infant with a weight of only around 2kg.

"One of the children has a complex congenital heart disease combined with cardiomyopathy. Due to physiological hypoplasia, the patient’s left ventricle is only one to two millimeters, which is very thin. There is also a child whose heart grows on the right side, and we need to put the donor on the right side.  These are all complicated situations that challenge  your technique.” Professor Nianguo Dong said.

Organ Care System: make more donor hearts "useable"

Organ Care System is a new technique used for donor heart transfer, which currently is still in the clinical trial stages. For heart transplantation, the biggest challenge at present is the shortage of donor hearts. In this case, the shortest time to send the donor heart to the operating room is a key factor for the success of heart transplantation.

Professor Nianguo Dong told us that in developed countries, heart transplant teams often have their own ambulance vehicles, private jets, and helicopters, in this way, maximum efficiency of procuring the heart can be guaranteed. However, in our country, such conditions are not yet available at present, and we mainly have to take public transportation. In addition, China’s territory is quite vast, so more time must be allocated for transporting of heart.

At present, the protection method of cold ischemia is still commonly used worldwide in heart transportation. This method is to place the heart in a mixture of ice and water at about 4 degrees above zero for preservation and transportation. However, in this process, it is inevitable that some degree of damage to the heart will occur. According to reports, many donor hearts have lost their use value by the time they are delivered to the patient due to poor preservation technology during transfer. Under this circumstance, breaking through the traditional bottleneck of donor heart transfer has become core to improve the efficiency of heart transplantation. At present, research on the preservation of donor hearts by normothermic perfusion is also being carried out in other countries, but it has not yet been applied to clinics.

Professor Dong's team led the development of Organ Care System

The Organ Care System machine being jointly developed by Wuhan Union Medical College Hospital and magAssist is expected to greatly extend this preservation time. According to Professor Ping Li of Wuhan Union Medical College Hospital, in contrast to the cold ischemia protection for heart transfer, Organ Care System can realize the transfer of the heart from one place to another while the heart is beating outside the body. In the Organ Care System, by adding the patient's blood and a certain amount of pre-filling fluid, extracorporeal circulation can be established for the donor heart. This allows the donor heart to remain working during the transfusion, which can minimize the damage to the myocardium, thus making the transfusion easier.

Professor Nianguo Dong pointed out that in addition to prolonging the transit time, for some donor hearts that do not function particularly well, they can be repaired to some extent by perfusion through the warm blood transfer system, and then transplanted when the condition improves." Through this technology, more donor hearts can be used effectively for Chinese heart failure patients."

According to Prof. Ping Li, the research and development of the warm-blood transfer system has been undergoing since five years ago. From initial concept update to material preparation, and machine design, the team members have been making constant revisions. At present, the third-generation product of the machine has been launched. Animal experiments have been successfully taken, and practical application experiments on humans will be conducted soon. 

Ventricular assist devices: making more patients 'afford to wait'

If Organ Care System is to make more donor hearts "usable", the role of the new ventricular assist device is to make more patients "afford to wait".For heart transplant patients, the biggest risk is that their hearts can't wait for a donor to arrive. Bridging refers to the establishment of extracorporeal circulation through a cardiac (ventricular) assist device to maintain the patient's life while the patient is waiting for a heart donor.

Speaking of cardiac assist devices, let's start with extracorporeal membrane oxygenation (ECMO). This device, which was only known to very few doctors, have become widely known during the COVID-19 pandemic. In fact, in the field of heart transplantation, many patients with end-stage heart failure have their hearts completely unable to work while waiting for a donor, or even suffer from cardiogenic shock. During this time, it is necessary to maintain circulation for them and at present, the device usually used in China is ECMO.

The core parts of extracorporeal membrane oxygenation (ECMO) are membrane lung (artificial lung) and blood pump (artificial heart). It can provide long-term cardiopulmonary support for patients with severe cardiopulmonary failure, winning precious time for rescuing those in severe conditions. However, for many patients with severe heart failure, their lungs do not have primary diseases, and the use of membrane lungs will cause damage to the blood coagulation system. Therefore, independent ventricular assist devices have become a new option for heart transplantation internationally in recent years.

According to reports, the short-term extracorporeal ventricular assist device (Extra-VAD) developed by Professor Nianguo Dong's team and magAssist. has entered clinical trials. Ventricular assist device is an electromechanical integrated centrifugal pump device. The core technology is to optimize blood compatibility and reduce complications through the systematic integration of fluid mechanics and actuating mechanisms. At present, the cutting-edge products in the world have not yet entered the Chinese market. The available centrifugal blood pumps for extracorporeal circulation are imported products using the previous generation of technology. 

As Professor Nianguo Dong said, this ventricular assist device has several conceptual innovations. First, it removes the membrane lung to better protect the blood; second, the design of the centrifugal pump is designed to have much less impact on the entire coagulation system and other systems of the patient. Using this device during the bridging phase is much simpler to manage, has fewer complications, requires less blood, and has a lower overall cost. It is a godsend for patients, doctors, and nurses.

It is reported that the ventricular assist device can also be used for the treatment and recovery of patients who cannot be separated from cardiopulmonary bypass after thoracotomy, as well as critical emergencies such as fulminant myocarditis and cardiac arrest caused by acute diseases such as H1N1, serious traffic accidents, and drowning, and can increase survival rate by 50%.

Team: Everyone is an specialist and an all-rounder

If it wasn’t from personal experience, we would never have imagined that a heart transplant team would need so many people. It is reported that there are currently more than 200 people in the heart transplant team of Professor Nianguo Dong, including preoperative evaluation team, extracorporeal circulation team, operation team, anesthesia team, ICU team, nursing team, logistics support team, administrative team, and other specialists from various disciplines.

"Compared with other fields, heart transplantation is a very difficult and demanding type of surgery. It wasn't easy for us to build the team we are today. In addition to medical talents, we also need to have assistants who specialize in contacting and buying tickets, assistants who are adept at laws and regulations..."Professor Nianguo Dong said that heart transplantation is an integrative discipline, and all disciplines must go hand in hand and all disciplines require a strong team.

Professor Shu Chen is the main person in charge of the OPO (Organ Procurement Organization) team. He told us that at present China adopts voluntary organ donation after brain death of citizens. His job is to keep in touch with colleagues inside and outside the province and ready to receive donated hearts at any time.

"Because the quality of donor heart is the most important factor affecting the success or failure of the operation, the members of our heart procurement team not only have to travel frequently, but also need to be in a state of being ready to leave at any time upon notification."Professor Shu Chen said that starting from the Heart Procurement team, the entire Heart transplant team has to start preparations one by one. "As soon as the heart procurement team boards the plane, the surgical team would start picking up the patient and prepare for the operation. The heart is a fragile organ and is quite sensitive to cold ischemia, so whether it is transfer or transplantation, we have to race against time."

"It can be said that everyone is a specialist and an all-rounder." Professor Shu Chen also told us that although the team members have different divisions of labor, almost everyone does not only have one specialty but is multi-skilled. In the case of when other colleagues are not available, it is necessary to substitute him/her without delay. "Without a strong team and an excellent leader, the work can't be done." He added.

Professor Ping Li also believes that the reason why the team can stand out among the peers in the country is largely due to the advanced concepts of Professor Nianguo Dong and the boldness of execution stems from superb skills. At the same time, they have a very rigorous scientific attitude when carrying out surgery and research.

Talking about the successful experience, Professor Dong focused on the following aspects:

First, the seniors of Wuhan Union Medical College Hospital have laid a good foundation for the development of heart transplantation. As early as 1994, the former director, Professor Chenyuan Yang, was the first in the country to carry out a heart transplant operation, and the patient lived 28 days after the operation. Another former director, Professor Zongquan Sun, performed the second heart transplant in the country, and the patient survived for more than a year.

Secondly, the team has the spirit of dedication and hard work, and everyone has indeed paid a lot of hard work for the benefit of the patients. According to media calculations, to escort the heart, the heart transplant team of Union Medical College runs more than 200,000 kilometers every year, which is equivalent to circling the equator five times.

The third is to have the spirit of perseverance. He said that the team also faced a lot of difficulties when doing heart transplantation at the beginning. In 2008, 6 cases were performed, 11 cases in 2009, 13 cases in 2010, and 12 cases in 2011. At that time, there were four to five years when the team was in a wandering state, but it was also an accumulation. Later, there were 32 cases, 48 cases, and more than 70 cases, and it slowly started up.

"Up to now, we did not achieve it overnight, but also had a slow development and slow experience accumulation process. Our reputation is built upon the process of improving the survival rate of patients." Professor Nianguo Dong said.