RU2844410C1 - Method for prediction of cardiovascular complications following coronary artery bypass surgery - Google Patents

Abstract

FIELD: medical science.

SUBSTANCE: invention relates to medicine, specifically to cardiosurgery and cardiology, and can be used for prediction of cardiovascular complications following coronary artery bypass surgery. Blood is drawn, thrombocytes are examined by flow cytometry. Examination is carried out before operation and in 3-5 days after operation. A platelet apoptosis index is detected by externalization of phosphatidylserine on their surface. If observing a decrease of this value by 20 % and less in relation to the preoperative level, a high risk of cardiovascular complications is predicted.

EFFECT: method provides an opportunity to increase the reliability and accuracy of predicting cardiovascular complications after coronary artery bypass surgery, due to the detection of an information-bearing marker, which is used to judge on the risk of cardiovascular complications, that is an indicator of thrombocyte apoptosis by externalization of phosphatidylserine on their surface.

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Description

The invention relates to medicine, more precisely to cardiac surgery and cardiology, and can find application in clinical practice for predicting the risk of developing cardiovascular complications.

Coronary heart disease (CHD) is the most important problem of modern cardiovascular surgery. Mortality from cardiovascular diseases in Russia is one of the highest in the world. One of the most effective methods of surgical treatment of CHD is aortocoronary bypass. Restoration of normal blood flow improves the condition of patients, which is confirmed by both laboratory and instrumental examination data and personal feelings. However, there is a risk of cardiovascular complications, which currently cannot be predicted accurately enough, either in the early stages or in the long term.

Currently, there is no assessment of long-term complications after coronary artery bypass grafting, and the patient's condition is judged based on standard laboratory and instrumental studies that reflect only the current condition. It is necessary to introduce a new biomarker that will be a predictor of cardiovascular complications in this group of patients.

A method for predicting clinical dynamics in patients with decompensated ischemic chronic heart failure (CHF) with systolic dysfunction of the LV is known (Patent No. 2770271, IPC G01N 33/50, published 2022). Prediction of clinical dynamics is carried out by analyzing the serum content of the serum biomarker LIGHT in patients using multiplex analysis.

When LIGHT levels of 30.05 ng/ml or more are detected in patients with acute decompensation of ischemic CHF with LV systolic dysfunction, the risk of developing adverse cardiovascular events is predicted.

The disadvantage of this method is that it is possible to make a prognosis only in patients who have already been diagnosed with CHF decompensation. Early risk prediction is impossible.

A method is known for predicting adverse cardiovascular events over 12 months in patients with chronic heart failure with recurrent angina after myocardial revascularization. The content of soluble ST2 is determined in the blood serum after the completion of the 6-minute walk test, based on which a high risk of developing adverse cardiovascular events is predicted. (Patent No. 2677611, IPC G01N 33/53, published 2019).

The disadvantage of this method is that it is impossible to make a prognosis in the early stages after the operation. In addition, the accuracy of the analysis suffers, since the patient's condition before the operation is not taken into account.

The closest method for predicting the postoperative course after CABG includes the study of platelets using flow cytometry (Pluta K, Porebska K, Urbanowicz T, et al. Platelet-Leucocyte Aggregates as Novel Biomarkers in Cardiovascular Diseases [published correction appears in Biology (Basel). 2022 Oct 24;11(11):1554. doi: 10.3390/biologyl 1111554]. Biology (Basel). 2022;11(2):224. Published 2022 Jan 30. doi: 10.3390/biologyl 1020224). Platelet and leukocyte aggregates bound by specific receptors are examined. They occur under conditions of severe stress, thrombosis, immune response, vascular damage and activation of leukocytes or platelets, and participate in the development of cardiovascular diseases (CVD). The increase in the level of these indicators is used to judge the risk factors for complications after surgery.

The disadvantage of this method is also its low accuracy, in addition, it does not allow identifying a group of people who need additional dispensary observation or preventive therapy.

The objective of the proposed invention is to eliminate the said drawbacks, increase the accuracy of forecasting by identifying a more informative marker by which the risk of cardiovascular complications is judged. Providing the ability to predict the personal risk of adverse cardiovascular events immediately after surgery. Identifying a group of patients who have undergone coronary artery bypass surgery for dispensary observation with the organization of effective targeted measures aimed at preventing the development of adverse cardiovascular events.

To solve the problem of predicting cardiovascular complications after coronary artery bypass grafting, including blood sampling, platelet testing by flow cytometry, it is proposed to conduct studies before surgery and 3-5 days after surgery. In this case, the platelet apoptosis index is determined by the externalization of phosphatidylserine on their surface, and when determining a decrease in this index by 20% or less relative to the preoperative level, a high risk of cardiovascular complications is predicted.

Platelets are direct participants in cardiovascular events, their condition is inextricably linked with a number of diseases, including coronary heart disease. Surface markers and, in particular, phosphatidylserine on the surface of platelets, which occurs exclusively during apoptosis, is a sensitive marker for a number of adverse cardiovascular events.

Platelets, as short-lived cells, quickly respond to changes in the body. Equally high levels of platelets in apoptosis before and after surgery indicate a high probability of cardiovascular complications. This method will allow us to determine the risk immediately after surgery and identify a group of high-risk patients who require careful follow-up to prevent the development of adverse cardiovascular events and prevent high premature mortality in these patients;

The method is carried out as follows.

When preparing the patient for surgery, blood is collected from the cubital vein using disposable systems in vacuum tubes containing 3.8% sodium citrate. After isolation by centrifugation, platelets were assessed by flow cytometry on a FACSCalibur device (Becton Dickinson, USA). Annexin-V-FITC fluorochromes with propidium iodide (BD Biosciences, USA) are used in accordance with the manufacturer's instructions. In this case, externalization of phosphatidylserine on the platelet surface was determined, thus assessing the percentage of platelets in apoptosis from their total number. A similar study is carried out 3-5 days after surgery. The risk of complications is predicted by analyzing the change in this indicator over time. If a decrease in apoptosis indicators by 20% or less is detected, a high risk of cardiovascular complications is predicted, and if the decrease is more than 20%, the prognosis is favorable.

An accurate prognosis of the disease course allows choosing the right treatment tactics, implementing preventive measures in the early stages after surgery. This ensures a reduction in the level of disability and mortality in this category of patients.

Example 1.

Patient D., 58 years old, was admitted to the cardiac surgery department 12 months after the onset of complaints of angina attacks and dyspnea during physical exertion. According to the ultrasound examination of the heart, no pathology was found. According to coronary angiography, there was subtotal stenosis of the anterior interventricular artery in the proximal third, 80% stenosis of the first diagonal artery at the mouth, and 70% stenosis of the right coronary artery. After the examination, a decision was made to perform surgical myocardial revascularization. Bypass grafting of the anterior interventricular, first diagonal, and posterior interventricular arteries was performed.

Before the operation and 5 days after the operation, platelet analysis was performed using the above-described method. The number of platelets in a state of apoptosis, measured by the externalization of phosphatidylserine index, before the operation was 42%, after 5 days it decreased to 28%. Prognosis: unfavorable postoperative course.

The patient was prescribed preventive drug therapy. However, the patient did not follow the recommendations.

A control study after 1 year revealed negative dynamics in the form of a decrease in the contractile function of the myocardium, the appearance of clinical manifestations in the form of shortness of breath, and chest pain during exertion.

Example 2.

Patient D., 63, was admitted to the cardiac surgery department 10 months after the first attack of angina pectoris with complaints of prolonged chest pain and severe dyspnea during physical exertion. According to coronary angiography, there is 80% stenosis of the anterior interventricular artery, 90% stenosis of the obtuse marginal branch at the mouth, and 80% widespread stenosis of the posterior interventricular artery. After examination, a decision is made to perform surgical myocardial revascularization. Bypass grafting of the anterior interventricular artery, posterolateral branch, and obtuse marginal branch is performed.

Before the operation and 3 days after the operation, platelet analysis was performed using the above-described method. The number of platelets in a state of apoptosis, measured by the externalization of phosphatidylserine index, before the operation was 46%, after 3 days it decreased to 21%. The prognosis is favorable postoperative course.

A control study after 1 year did not reveal any positive dynamics in the form of an increase in the ejection fraction or an increase in tolerance to physical activity. The patient has no complaints.

Example 3.

Patient M., 60 years old, was admitted to the cardiac surgery department 2 years after stenting of the anterior interventricular artery with complaints of angina attacks and dyspnea during physical exertion. According to coronary angiography, there is 90% stenosis of the left coronary artery at the orifice, and 80% stenosis of the first diagonal artery at the orifice. After examination, a decision is made to perform surgical myocardial revascularization. Bypass of the anterior interventricular and diagonal arteries is performed.

Before the operation and 4 days after the operation, platelet analysis was performed using the above-described method. The number of platelets in apoptosis, measured by the externalization of phosphatidylserine index, was 41% before the operation, and decreased to 21% after. Prognosis: unfavorable postoperative course.

A control study after 1 year revealed negative dynamics in the appearance of angina symptoms and a decrease in the left ventricular ejection fraction.

The proposed forecasting method was used in 20 patients undergoing treatment for coronary heart disease with multivessel coronary artery disease, for whom coronary artery bypass grafting was indicated. All patients underwent surgery and were discharged on the 7-10th day with improvement. A favorable prognosis was noted in 16 patients, requiring no special features in further observation. In four cases, the prognosis was unfavorable, which required a more aggressive therapeutic approach to treatment and more frequent observation. Control examinations within 1 year confirmed the prognosis in all cases.

The proposed method increases the reliability of the prognosis of the postoperative course of the disease, which allows for more effective treatment of this category of patients, improving the quality and duration of their lives. Thanks to this method, it becomes possible to determine a group of high-risk patients and begin early preventive measures, which will reduce the disability and mortality rates among patients with this disease.

Claims (1)

A method for predicting cardiovascular complications after coronary artery bypass grafting, including blood sampling, platelet testing using flow cytometry, characterized in that the testing is performed before surgery and 3-5 days after surgery, while the platelet apoptosis index is determined by externalization of phosphatidylserine on their surface, and when determining a decrease in this index by 20% or less relative to the preoperative level, a high risk of cardiovascular complications is predicted.