Prof. Dr. Yoto Yotov is a specialist in internal medicine, cardiology, public he alth and he alth management. He graduated in medicine in 1988 at the Medical University of Varna. He worked as a ward therapist 1988-1993 in Burgas. Since 1993, he has been an assistant, senior assistant, chief assistant, and since 2012 - an associate professor at the First Clinic of Cardiology, at the Department of Cardiology and the Department of Internal Medicine of the Medical University-Varna.
He has acquired speci alties in internal medicine (1994), cardiology (1998), public he alth and he alth management (2000). In 1993, he obtained a Master's degree in Noncommunicable Disease Epidemiology and Biostatistics at Erasmus University, Rotterdam, the Netherlands.
He specialized in the Netherlands and Switzerland. In 2007, he defended his thesis on the topic "Assessment of the global cardiovascular risk for the development of ischemic heart disease in women" and was awarded the scientific and educational degree "doctor".
In 2009, he acquired the title "Specialist in Hypertension" from the European Society of Hypertension. He is a member of the European Society of Cardiology, the European Society of Hypertension, the European Association for Cardiac Imaging, the European Association for the Prevention and Rehabilitation of Cardiovascular Diseases, the European Association for Heart Failure.
He is a member of the Board of Directors of the Society of Cardiologists in Bulgaria and former chairman of the Working Group on Echocardiography of the Society of Cardiologists in Bulgaria, member of the Board of the Heart-Lung Association, Varna, secretary and member of the Board of Directors of the Association of Echocardiography Specialists "Varnaeho", Varna.
In 2014, he was the director of the hypertension summer school organized by the European Hypertension Society. His main scientific interests are in the field of prevention and imaging of cardiovascular diseases, hypertension, heart failure.
He has participated in many clinical trials of drugs in cardiology since 1994, being the national coordinator in two of them, and a member of the International Steering Committee (STEERING COMMITTEE) in three.
He has over 40 publications and 60 participations in scientific congresses.
. We talk to Prof. Dr. Yoto Yotov about the latest treatment for symptomatic heart failure with preserved cardiac ejection fraction.
Prof. Yotov, a medication is now available in Bulgaria, which is defined as the first and only therapy approved in Europe for the treatment of adult patients with symptomatic heart failure. Can you explain more exactly how this medication works? What is the effect of applying it?
- At the beginning I want to make an important clarification. The message applies to patients who have symptomatic heart failure with preserved ejection fraction. This medication was approved for use and is prescribed by the He alth Insurance Fund for patients with a reduced ejection fraction - i.e., the group of more seriously ill patients.
We are talking about the drug empagliflozin, with the trade name Jardines, which belongs to the group of diabetes drugs, such as inhibitors of a cotransporter in the kidney known as SGLT2. It is a sodium-glucose cotransporter that acts in the kidney and leads to the excretion of glucose, sodium and fluids. That is, it also has a diuretic effect.
Initially, this group of medications was registered and used as an oral antidiabetic agent. But then extensive research, initially in the diabetic group and subsequently in non-diabetic patients, showed that this drug has a beneficial effect in patients with symptomatic heart failure, against the background of the rest of their already established therapy.
It was originally used and tested, as already mentioned, in patients with heart failure with reduced ejection fraction - that is, with reduced pumping function of the heart. And its benefit has been proven in terms of reducing hospitalizations due to heart failure and cardiovascular mortality, as well as improving the functional status and quality of life of these patients.
A year and a half ago, favorable results were also published that the medication also affects patients with symptoms of heart failure, in whom, however, we do not have a violation in the pumping function of the heart. Uniquely, this is the first drug to demonstrate benefit in this subset of heart failure patients in reducing heart failure hospitalizations and cardiovascular mortality, as all others used to treat heart failure have so far failed to show such advantage.
These results give us great hope, as it could enable cardiologists to use the drug across the spectrum of heart failure patients, regardless of their pumping function - whether it's reduced, whether they have diabetes or not. This can change the prognosis of these patients, as well as, of course, their symptoms.
In our previous conversation, we emphasized untreated and poorly controlled hypertension as a risk for heart failure. Now you are paying attention to diabetes mellitus, not only as a major risk factor for the development of heart failure, but also that the disease worsens the prognosis in such patients. Could you please explain what is the relationship diabetes mellitus - heart failure?
- The connection, to a large extent, is clear. Both arterial hypertension and diabetes mellitus are generally a major risk factor for the development of cardiovascular diseases. On the one hand, diabetes mellitus leads to more severe and earlier atherosclerosis, with the development of ischemic heart disease, which in its final stage leads to heart failure.
On the other hand, there is already evidence that diabetes itself and its metabolic disorders lead to direct damage to the heart and to the so-called diabetic cardiomyopathy – damage to the heart muscle from diabetes itself, which leads directly to manifestations of heart failure.
Note that this achievement with the drug empagliflozin for the treatment of heart failure patients with preserved ejection fraction is very large, since the majority of phenotypically manifested patients with this subtype of heart failure are precisely diabetics. But the interesting thing is that this one, basically created, as I already mentioned, as an antidiabetic drug, shows the same effects, regardless of whether the patient has diabetes mellitus or not.
This is proof that the drug really has a great future. Second in importance, if we have to make the link again with diabetes mellitus, is that the drug also has a protective function in relation to the kidneys - it reduces the damage to kidney function as a result of diabetes mellitus. This is extremely important for these patients. The problem is that, in addition to cardiovascular diseases, another big scourge for this group of patients is the development of kidney failure during the course of the disease.
Prof. Dr. Yoto Yotov
Why are women with diabetes at a higher risk of developing heart failure than men?
- In general, the female gender is, how should I say, a little more damaged and with a greater potential risk of heart failure, because the metabolic disorders that occur as a result of the development of diabetes mellitus, to a greater extent damage the female organism.
Of course, the intimate mechanisms of this process are not completely clear, we do not know why this happens. But one of the reasons is that diabetes mellitus with its metabolic disorders leads to the fact that the protective function of female sex hormones is reduced. That is, it appears as a counterbalance to their positive role for women.
First, they are identified as the main reason women live longer. And secondly, the complications of cardiovascular disease in women usually occur between 5 and 10 years after those of men, precisely thanks to the protective function of female sex hormones. However, the occurrence of diabetes mellitus in women actually nullifies this benefit of female sex hormones and makes them equal and even more likely to develop cardiovascular disease in the presence of diabetes than in men.
Why does heart failure with preserved ejection fraction have a worse outcome than that with reduced function?
- I would not say that heart failure patients with preserved ejection fraction have a worse prognosis than those with reduced ejection fraction. But we still have to keep something else in mind: the prognosis, at best, is almost as bad as for those with a reduced ejection fraction. However, recent data suggest that there may be a slightly better prognosis in these patients.
But in general, the development of heart failure, regardless of the ejection fraction, is an extremely unfavorable disease in humans. The five-year survival of patients after the onset of heart failure, whether with preserved or reduced ejection fraction, is at best just over 50%.
That is, approximately 40% of patients die within 5 years, regardless of the ejection fraction. So the idea is basically to protect the development of heart failure as much as possible.
That is why the treatment of both diabetes and hypertension is extremely important precisely as a protective factor for the development of heart failure. And now, when it has developed, new opportunities are being sought, which the drug empagliflozin now gives us.
As a medicine, it has another advantage, apart from the benefits I mentioned before – its intake is extremely convenient. Unlike other medications, empagliflozin does not require dose titration. The dose is only one - 10 mg, and there is no need to increase or decrease, which makes it extremely convenient to take.
Secondly, its side effects are quite few - they are comparable to those of a placebo. So it is a relatively safe medication, which really gives a future to the preparation and its use in the practice of doctors in Bulgaria, and not only here, of course.
Are there already approved protocols for its implementation?
- For patients with a reduced ejection fraction in Bulgaria, there is permission from January 1st for two medications, one of which is empagliflozin, indicated for heart failure and chronic kidney disease
That is, it can be written with a discount from the He alth Insurance Fund, with a reimbursement of 75%. There are still no established protocols in Bulgaria for the administration of the medication in patients with heart failure with preserved ejection fraction, as the decision of the European Association has just arrived. You know these things take a little more tech time. But I hope that by the end of the year the authorization will also be received for its use with reimbursement in patients with a preserved ejection fraction.
What are the challenges and what is more specific in the diagnosis of heart failure patients with preserved fraction?
- Often this diagnosis is quite difficult because it requires a little more attention and searching on the part of the doctor for the cause of the patient's symptoms. Because in most cases, when a patient has shortness of breath - the most common symptom of heart failure, and the doctor found that there is a violation in the pumping function of the heart, he somehow associates these symptoms with the corresponding disease. But when the patient has shortness of breath, especially during physical exertion, and the doctor sees that the pumping function is preserved, he begins to look for some other reasons for the complaints and does not associate them with heart failure with a preserved ejection fraction.
This, on the one hand, delays the diagnostic process, as well as the timely establishment of the diagnosis and the search for an adequate solution to the problem. On the other hand, the very diagnosis of heart failure with a preserved ejection fraction is much more complicated.
I often give the following example: usually in patients with a reduced ejection fraction the echographic criteria that we, cardiologists, are based on are at best 3-4, while in those with a preserved ejection fraction all international associations describe up to 22 criteria to be observed and fulfilled in order to make the correct diagnosis. That is, there is a step-by-step way of making the diagnosis, which means that it is much more difficult. But every doctor who comes across a patient with the relevant symptoms should also think about the possibility that he also has heart failure with a preserved ejection fraction.
You define it as heterogeneous suffering. What do you mean?
- This is because, unlike heart failure with a reduced ejection fraction, here the symptoms are phenotypically different in terms of appearances and aspects. For example, some patients are women who may or may not have hypertension and diabetes mellitus, as well as a faster heart rate.
Another phenotype is, for example, men who are overweight, have sleep apnea, but have a preserved ejection fraction and no ischemic heart disease. That is, the variety of phenotypic manifestations in this heart failure with a preserved ejection fraction is much greater, and this leads somewhat to difficulties in the diagnosis itself.
While usually patients with heart failure with reduced pumping fraction are men over 60 years old, most often with ischemic heart disease. That is, they as a group are much more clearly distinguishable and more pronounced as a phenotype, while the subgroup with preserved push fraction is much more heterogeneous and diverse.