Cancer and heart disease

Cardioncology – a new clinical discipline

Anastasia Penzina, "Scientific Russia"

At the last general meeting of professors of the Russian Academy of Sciences, an incredible impression was made by the report of a corresponding member of the Russian Academy of Sciences, cardiologist Simon Teimurazovich Matskeplishvili.

Thanks to the development of medicine in the world, mortality is noticeably reduced. Today, 15 million people have been cured of cancer in the USA alone. Cancer is no longer a sentence. However, cancer treatment affects the cardiovascular system. Chemotherapeutic agents and radiation therapy cause cardiotoxic effects after treatment. All this leads to the fact that mortality from heart failure is higher than from cancer. And patients, sometimes, simply do not know that certain drugs that save from cancer can cause irreparable damage to their heart. Simon Teimurazovich is sure that oncologists and cardiologists need close cooperation. For this, Russia needs a program of a new fundamental clinical discipline – cardioncology.

– At the last general meeting of professors of the Russian Academy of Sciences, you made an interesting report on a new discipline – cardioncology. What kind of discipline is this and why has it started to develop?

– I'll start from afar. Every year we treat cardiovascular diseases better and more effectively, which has become the main reason for a significant increase in people's life expectancy. On the other hand, today we know for sure that the longer a person lives, the greater the likelihood of cancer. Unfortunately, age and cancer are inextricably linked. There is even such a saying, slightly cynical: if a person did not die of cancer, then he simply did not live to see it.

Thus, it is impossible to simultaneously increase life expectancy and achieve a reduction in the incidence of cancer, at least for biological reasons.

Of course, along with cardiovascular diseases, we have become better at treating oncological diseases. This is both standard chemotherapy and targeted therapy, when drugs selectively affect the tumor. Among the new directions, immunotherapy based on the activation of the human immune system as a whole or against specific cancer antigens can be distinguished. This allows her to better recognize malignant cells and kill them. At the same time, when we significantly increase the overall activity of the immune response, the body can start working "against itself", leading to autoimmune complications due to damage to healthy tissues.

Of course, there are other methods of treatment, such as surgery, as well as radiotherapy – radiation, radioisotope, proton, carbon, boron-neutron capture. The latter are used in special cases, for example, in the treatment of brain and spinal cord cancer, eye tumors, tumors in young children, etc.

But with the advent of progressive approaches to the treatment of oncological diseases, it became clear that many cancer treatments have an extremely negative effect on the cardiovascular system. Moreover, today it is known that about half of the deaths among cancer patients are caused not by the disease itself, but by the so–called cardiotoxicity of treatment - damage to the heart or blood vessels as a result of exposure to some type of therapy.

This fact was the reason for the emergence of a new discipline – cardioncology. And we are not talking about a specialty that deals with heart oncology by analogy with neuro-oncology or oncogynecology. We are talking about a discipline that aims to identify problems of the cardiovascular system, to prevent and treat them in patients with an already established diagnosis of cancer, as well as in those patients who have had cancer. For example, today in the United States alone, about 15 million people have either recovered from cancer or continue treatment, turning this once terrible disease into a chronic form. But often these same patients get an appointment with cardiologists who do not always understand how and from what to treat them.

This problem is extremely relevant in our country. Moreover, quite a lot of cancer patients have a cardiological diagnosis: coronary heart disease or a previous myocardial infarction, cardiac arrhythmia and conduction, pathology of heart valves, high blood pressure. And when an oncologist is approached by a patient with stomach cancer, whose medical history mentions a myocardial infarction that was once suffered, the doctor fears that the patient may not survive the operation, and if he survives, then with significant complications. Therefore, the oncologist directs the patient to consult a cardiologist in the hope that he will give his recommendations for a successful outcome of the operation.

The cardiologist, being quite capable of helping such a patient in another situation, seeing the main diagnosis: stomach cancer with metastases, often refuses to treat such a patient or give permission for serious oncological intervention – he does not want to take responsibility for its outcome. And such a patient goes from one doctor to another in search of a way out of, as they explain to him, an extremely difficult situation. But time goes by, and the oncological disease "does not wait", but actively develops, sprouting into the surrounding tissues, or metastasizes. And often the decision-making process is delayed so long that the oncologist is simply no longer able to operate on the patient or prescribe chemotherapy. The same problem may arise when choosing targeted or radiation therapy. There are hundreds of thousands of such patients in our country who need help today. And, most surprisingly, there is nothing complicated about it. Back in 1999, my Italian colleagues and I developed and published in a leading international journal a technique that allows us to identify a group of patients who can be safely operated on even with a serious cardiological diagnosis. And these are the majority, but they are still denied treatment to this day.

Therefore, I would like to ask an extremely important question – can it be considered ethical to start cancer treatment without consulting each patient with a cardiologist? After all, this can prevent serious consequences for his cardiovascular system. The probability of successful cancer treatment is already quite high today, and heart failure or another cardiac complication of such treatment, strange as it may sound, is not at all easier than the oncological disease itself. And it is the cardiological diagnosis that will determine the prognosis of later life, and not the transferred oncological disease. Moreover, heart problems caused by antitumor treatment are not always amenable to standard methods used in cardiology.

Solving these complex issues requires a new approach, new knowledge and research, which formed the basis of the specialty of cardiology. This is an interdisciplinary field at the junction of not only medical specialties, such as oncology, cardiology, radiology and so on, but also physics, chemistry, mathematics, psychology and many others. Individual specialized centers, whether oncological or cardiological, are not able to solve such a task alone. Cardioncology, as well as all modern medicine, is a university, academic science, so we are actively developing this direction at Moscow University. I really hope that the Russian Academy of Sciences will be actively interested in them.

The participation of the Ministry of Health is very important, since the introduction of a cardioncological service will require a revision of approaches to providing medical care to many oncological patients. Already today, in most of the leading cancer centers in the USA and Europe, the first consultation of such patients is conducted jointly by an oncologist and a cardiologist. Together they choose the protocols of chemotherapy and surgery, observe the patient throughout the course of treatment.

– You mentioned foreign countries. Are there similar examples in Russia?

– Of course there is. But it is important to note here that the direction and discipline in our country are beginning to develop, and there are no specialists yet. We don't have such a cardiologist yet. As, indeed, in the rest of the world. This is both good and bad at the same time. On the one hand, there are no specialists, there are no training and retraining programs, there is no established service to provide assistance to a large number of patients. And on the other hand, there is a real opportunity to become the first and leading country in the world to adopt a national cardiology program to unite the efforts of various doctors in the joint fight against a serious illness. This, of course, implies large-scale scientific research in this area, and the development of completely new methods of prevention, diagnosis, treatment and rehabilitation of patients with cancer.

Today, such opportunities exist only in some medical centers in Russia, we actively contribute to the development and expansion of the geography of cardioncological consultations. For example, our Medical Center of Moscow State University closely cooperates with the Russian Cancer Research Center named after N.N. Blokhin in the field of identifying the risks of complications before oncological operations in patients with an established diagnosis of cardiovascular disease. Also, together with the Herzen Moscow Cancer Research Institute, we are conducting an important clinical study, during which we remotely monitor the condition of cancer patients using miniature portable devices - recorders of vital human parameters. We developed these truly unique devices at Moscow University in cooperation with our industrial partners. The small device is fixed on the patient's body and continuously monitors the indicators for an unlimited time and instantly transmits information to our server. Since one of the first manifestations of cardiotoxicity is most often arrhythmia, for the automatic analysis of the data obtained, we have developed an algorithm based on artificial intelligence technology that allows us to detect the earliest and clinically non-manifest cardiac arrhythmias with high accuracy in order to summon the patient in time and begin a full-fledged cardiological examination.

Cardionkology is also actively developing in other institutions – there are departments of cardionkology at the I.M. Sechenov First Moscow State Medical University and the A.I. Evdokimov Moscow State Medical and Dental University. Specialists from St. Petersburg, Novosibirsk, Tyumen are working in this direction. Such practical work is also extremely important.

But, nevertheless, I believe that individual, even fairly large and well-equipped centers, will not be able to solve such a global problem. Therefore, in order to implement regional pilot projects to create a cardioncological service, including one that actively uses our telemedicine developments, we discussed such opportunities with the Ministry of Health of the Rostov Region, with the leadership of the Ryazan region and our colleagues in Ryazan and came to a positive decision. It turned out that this is not so difficult. It is more difficult to figure out how to bring information to patients who need to understand when and where to contact them.

I am sure that the implementation of such a program in Russia is able to save the lives and health of hundreds of thousands of patients. Today, if you'll excuse the cynical expression, they are actually homeless. Neither oncologists nor cardiologists often do not know how to help them, and simply refuse treatment. There is such an expression – "fear does not stop death, it stops life" – so, first of all, you need to remove this fear and take the first step so that the seemingly cumbersome tangle of problems unravels in an elementary way. It is also extremely important to know that in addition to being able to predict the development of cardiotoxicity and detect it at the earliest stages, we can treat it – the appointment of certain basic and practically safe cardiological drugs in many cases helps to cope with damage to the cardiovascular system caused by one or another type of antitumor therapy.

I will give some illustrative and important examples for our country. There is a certain form of the disease, the so-called HER2-positive cancer, which occurs in about a quarter of all patients with this disease, that is, in many millions of women around the world. For its treatment, a special targeted therapy has been developed based on drugs that block HER2 receptors on tumor cells, preventing them from dividing and metastasizing. But it turned out that the same receptors are located on the heart cells. They are responsible for maintaining the viability of cardiomyocytes and ensure the balance of intracellular calcium and the integrity of contractile proteins. Therefore, when we block these HER2 receptors on tumor cells to treat cancer, we significantly increase the likelihood of cardiomyocyte damage.

Another illustrative example is a widespread and rather severe hematological disease – chronic lymphocytic leukemia, which annually takes the lives of hundreds of thousands of patients. Targeted therapy has also been developed for its treatment, which has radically changed the fate of many people. They take one capsule a day and almost forget about their diagnosis, continuing a normal life. But these drugs have a downside: one of the possible side effects is a violation of the heart rhythm – atrial fibrillation, aka atrial fibrillation. For a patient, such an arrhythmia in itself is not dangerous, however, when an oncologist sees its appearance, he often suggests interrupting chemotherapy to restore the rhythm, or simply waiting for a cardiologist's consultation. At the same time, the longer the break in treatment, the higher the probability of relapse of the disease, and the lower the possibility of successful repeat therapy. That is why in this situation, it is extremely important to establish contact between a chemotherapist and a cardiologist, who can determine that the arrhythmia is not dangerous and give permission to continue the main treatment.

These examples, like many others, emphasize the complexity of the problem, which, nevertheless, is quite solvable if you start to deal with it. As I have already said, it is important that the Russian Academy of Sciences pay attention to this issue. Once again, neither a leading cancer center nor a leading cardiology center are capable of coping with such a task alone, since not only doctors of various specialties, but also mathematicians, physicists, economists, lawyers, psychologists and many other scientists must work in the field of cardiology.

To predict and early identify patients at high risk of developing cardiotoxicity, it is necessary to apply big data analysis technologies using machine learning systems and artificial intelligence algorithms; it is necessary to develop innovative diagnostic techniques based on new physical principles; to introduce legal, economic, ethical, social and psychological approaches in this field of science and clinical practice; to study and offer a variety of treatment options for cardiac complications of cancer treatment. The Russian Academy of Sciences is perhaps the only scientific organization that unites specialists in each of these areas. No less important is the role of scientific and educational organizations, primarily the leading university of Russia - Moscow University, both in conducting scientific research and in training specialists and developing educational programs and standards in the field of cardiology, which are simply not there now.

Such an approach would allow our country to make a real global breakthrough in the entire world of science and medicine.

– How did it turn out that chemotherapy and other cancer treatments negatively affect the heart? Who first sounded the alarm – oncologists or cardiologists?

– It is difficult to say who sounded the alarm first. Personally, I became interested in this topic back in the 90s, more than 25 years ago, and even then it was known that, in particular, anthracyclines have significant cardiotoxicity. Actually, the correct name of this group of drugs is anthracycline antibiotics, since they have both high antitumor and antimicrobial activity. But, as data on the success of their treatment of various forms of cancer accumulated, reports began to appear that they seriously affect the cardiovascular system, causing severe heart failure.

This was the first real challenge for doctors, because having cured the tumor, we, nevertheless, can lose a person. Since then, many absolutely amazing drugs have appeared that allow, if not completely cure some forms of cancer, then transfer the disease to a chronic form, prolonging the patient's life for many years. But, as it turned out, one of the most formidable complications of their use were disorders of the cardiovascular system, not limited only to the development of heart failure. Certain drugs can cause severe, including life-threatening, cardiac arrhythmias, which can lead to sudden death. Other drugs lead to severe coronary artery spasms and myocardial infarctions. Unfortunately, the list of complications is extensive – severe arterial or pulmonary hypertension, venous thrombosis and pulmonary embolism, severe bleeding, and so on.

– Do oncologists warn patients about complications affecting the heart?

– Oncologists often say that if a person does not have cancer, then he is healthy. And they believe that heart failure, which can develop in him a few years after chemotherapy, is an incomparably smaller problem compared to a large tumor. That's not so. I am sure that today we must think about how to cure cancer, and about what the quality of life of the patient will be in 10 years. But in the rapidly changing paradigm of modern medicine, it is very difficult to implement this. The healthcare systems of developed countries are focused on the number of treated patients, not the quality of treatment. The increasing burden on doctors leads to a catastrophic lack of time, especially for the most important thing – a direct and direct dialogue between the doctor and the patient. Therefore, medicine is becoming quasi–instrumental - doctors treat people less and less and more often treat blood tests, cardiograms, tomography, endoscopy, biopsy, etc. And it is necessary to think about what will happen to the patient in 10 years, and not in a week, more and more often. And discuss with him all the issues of later life.

Of course, it is impossible to cure the disease by talking alone, but this is the only way to understand a person's soul, dispel his fears and doubts, and help cope with a serious illness. After all, many people are afraid of dying from cancer, but few people imagine the severity of diseases of the circulatory system. But the trick is that today cancer is not a verdict. Therefore, it is very important not only to convey to a person that he is curable, but also to choose a treatment for him that will protect his cardiovascular system.

Therefore, in my opinion, it is unethical to begin treatment of a patient with cancer without discussing with him the possible risks from the heart, so the patient must necessarily consult a cardiologist. In Russia, this happens extremely rarely, except in large cancer centers, which already understand that patients often die not at all from what they are being treated for.

There is a well–known joke: a doctor asks a colleague: "Does it happen to you that you treat a patient from one, and he dies from another?" "No," he says. I'm a good doctor – what I treat, that's why he dies."

Given the achievements of modern oncology, this is exactly the situation – patients are treated for cancer, and they die from heart problems. And we, cardiologists, can prevent this and help our colleagues.

– And if the oncologist says nothing about the risks of treatment, can the patient himself take the initiative and go to a cardiologist?

– Oncologists, of course, discuss the risks of treatment with patients, but this is often limited to the prevention of infectious complications or hard–to-bear side effects - nausea, vomiting, hair loss, weakness. Cardiological problems are rarely affected if there is no already established diagnosis of cardiovascular disease.

It is in the best interests of the patient himself to take care to preserve his health as much as possible. There is a high probability that his cancer will be cured, and in a few years his prognosis and quality of life will directly depend on the state of the cardiovascular system.

Therefore, the patient should take the initiative and ask the oncologist a question – are there any drugs toxic to the heart in the treatment protocol? How can I protect myself? How often do I need to be checked? Do I need to change the regimen of taking cardiac medications? It is important to understand that not all chemotherapy drugs are cardiotoxic, cancer immunotherapy does not always lead to myocarditis, radiation therapy does not necessarily cause damage to the heart valves or pericardium. In general, the frequency of pronounced cardiotoxicity is about 5-8%. But due to the fact that a huge number of people are covered by treatment, the number of patients is growing avalanche-like.

An oncologist may answer that a cardiological examination is not included in the standard of medical care and, accordingly, is not paid. Then the patient must independently find an opportunity to get a cardiologist's consultation. Therefore, I hope that our state will pay close attention to this problem, and regulatory documents will appear that will include regular examination of the cardiovascular system in the protocol for the treatment of oncological diseases.

The National Healthcare Project is being actively implemented in Russia, one of the target indicators of which, in particular, is to reduce mortality from diseases of the circulatory system to 450 cases per 100,000 population by 2024. Is it a lot or a little? For comparison, I will give some data – for example, in many European countries today this indicator is less than 100, in France and Italy – about 50. In the USA, the death rate of 450 cases per 100,000 population was reached in the early 70s of the last century, and this is more than 45 years ago. Therefore, we have something to strive for and, from my point of view, without a global solution to the problem of cardiovascular toxicity in the treatment of oncological diseases at the national level, it will be extremely difficult to achieve targets.

– What needs to be done now to save that part of the patients that you called homeless?

– Firstly, once again I apologize for such a cynical and possibly disrespectful term in relation to a huge number of really unhappy people. But there is no other way to call them. It is quite obvious that given the significant attention to the problem of cancer treatment in our country, a situation will inevitably arise in which the better oncologists treat their patients, the more of these patients we cardiologists will have. And Russian cardiologists are completely unprepared for the treatment of such patients.

Therefore, it is important to convince the state authorities that the problem exists, that there is a specific and considerable group of patients who need help. But patients should also take the initiative, which means they should be aware of their condition and the possible risks of treatment. Unfortunately, the mentality of people is arranged in such a way that many are ready to change the model of a mobile phone every few months, and at the same time stand in line for free medications at the polyclinic for a long time. People should understand that they are responsible for their own health – not an oncologist, cardiologist, health minister or even the president of the country. A person should take care of himself, this is his right, but also his duty. This requires a certain culture of attitude to one's health, which we, for the most part, do not have yet.

If we talk specifically about cardioncology, a patient with cancer should strive to get advice from a cardiologist before starting treatment. In many cases, a cardiologist will say that the risk is small, that everything will go well, tell you how to protect the heart and blood vessels or prescribe treatment. But, more importantly, this word and the support of a cardiologist can be a real help for both the patient and his oncologist. It will strengthen his faith, motivation to live, strength to fight cancer.

Yes, we have an unprecedented crisis of trust in our society – today people do not believe doctors, do not believe journalists, law enforcement agencies, teachers or ministries – they do not believe anyone. Therefore, for the successful implementation of such a project, the assistance of the country's top leadership is extremely important.

Unfortunately, anyone can get cancer. And it would be unfair and wrong if, after fighting cancer, he dies of heart disease. Today we have the knowledge and capabilities to help a large number of patients. In our Medical Center of Moscow State University, highly qualified specialists with a worldwide reputation work, unique equipment is concentrated, we are actively developing the cardiology service, helping every person who turns to us for help. Today we can both prevent the problem and identify it at the earliest stage and cure the patient.

I believe that both the Russian Academy of Sciences and Moscow University have every opportunity to implement the national cardiology program. It can be carried out only at the academic interdisciplinary level. My deep confidence is that together we will save hundreds of thousands of people. This, of course, will require additional funding, changes in the work of many medical structures. More recently, the chairman of the Accounts Chamber, Alexei Kudrin, announced that more than 1 trillion rubles remained unspent from the 2019 budget. In this sense, I have a spoiled psyche – when I see money not spent, as well as improperly spent, I instantly translate it into the number of people who could be saved. Human life is the highest value. But it can also be expressed in money for a doctor's consultation or for a drug. Therefore, the authorities should think about it. It is important. Now is the time – we need to move from words to deeds.

About the author:
Simon Teimurazovich Matskeplishvili – Doctor of Medical Sciences, Professor, Corresponding Member of the Russian Academy of Sciences, Deputy Director for Scientific Work and Head of the Department of Information Technologies in Biomedicine of the Medical Research and Educational Center of Lomonosov Moscow State University.

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