RU2716749C1 - Method for predicting the progression of chronic cardiac failure within a year after a previous myocardial infarction - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to cardiology, and can be used to predict progression of chronic cardiac failure (CCF) within one year after a previous myocardial infarction. In 6 months after myocardial infarction, blood is sampled and erythrocyte beta adrenoreactivity is determined. If observing erythrocyte adrenoreactivity values – β-ARM is more than or equal to 49.53 standard units, progression of chronic cardiac failure is predicted. If observing values of β-ARM below 49.53 standard units, predicted favorable course of disease.

EFFECT: method provides more accurate prediction of CCF progression within a year after myocardial infarction by evaluating the β-ARM, which is an early predictor of CCF progression in the patients.

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Description

The invention relates to medicine, namely to cardiology.

Chronic heart failure (CHF) is one of the most important medical and socio-economic problems of the present. The prevalence of CHF in the Russian Federation ranges from 4.9 to 8.5%, while NYHA (Classification of the New York Heart Association) accounts for 1.8 to 3.1% of severe CHF of the III-IV functional class (FC) [1]. Considering that. that the proportion of patients with heart failure in the population remains high, and the progression of symptoms contributes to a high risk of hospitalization and mortality in this category of patients, the search for new predictors of the risk of adverse outcomes in patients with heart failure remains relevant [2]. Taking into account the fact that often the root cause of heart failure is a previous myocardial infarction (MI), the study of patients with heart failure who have had MI is of the greatest interest both for science and for practical public health, especially in the era of updating the arsenal of diagnostic methods and tactics management of patients with acute coronary pathology [3].

Currently, in our country there are a number of works devoted to the problem of studying the red blood cell adrenoreactivity in various cardiovascular pathologies, but among them there are relatively few works that focus on heart failure. Single works indicate the prognostic value of the erythrocyte beta-adrenoreactivity indicator to assess the severity of CHF [4-7]. Analysis of the average values of beta-adrenoreactivity in these studies showed a significant excess in patients with more severe chronic heart failure, as well as with chronic heart failure of ischemic origin. At the same time, a universal method for assessing the progression of heart failure by analyzing beta-adrenoreactivity of red blood cells in patients with MI was never developed.

There is a method of evaluating red blood cell adrenoreactivity by changing the erythrocyte sedimentation rate, characterized in that the determination is carried out under the action of adrenaline in vitro in several concentrations against the background of their beta-adrenoreceptor blockade with beta-blocker obzidan added to the studied citrate venous blood [8]. The disadvantage of this method is that the studies were carried out to identify certain groups of people potentially capable of developing a stress response, mainly athletes and students during exams, as well as to predict the therapeutic effect of inhibitors in patients with cardiovascular pathology. This method does not reflect the possibility of applying the methodology for determining beta-adrenoreactivity of erythrocytes in patients with severe cardiovascular pathology, such as heart failure, in particular, in combination with the transferred MI.

An adequate prototype was not found in the analyzed patent and scientific medical literature.

The objective of the invention is to develop a highly informative method for predicting the progression of heart failure within a year after MI.

The problem is solved by determining the beta-adrenergic reactivity of red blood cells 6 months after MI transferred to the model of red blood cells in a small volume of venous blood by a method based on a change in the osmotic resistance of red blood cells under the influence of beta-blocker. When identifying the indicator β-AWP≥49.53 srvc predict the risk of progression of heart failure within a year after MI.

The proposed method for predicting the progression of heart failure after myocardial infarction is based on the assessment of the destructive effect of catecholamines on the membrane structures of cells. Under conditions of prolonged and strong stimulation by catecholamines, the number of adrenergic receptors on the erythrocyte membrane decreases and their functional state, the general biological phenomenon of desensitization of the cell membrane, changes. This fact is a reflection of the single principle of the neuroendocrine system - the principle of "feedback: the higher the level of catecholamines in the blood, the fewer receptors on the cell membranes. Accordingly, with an increase in the blood of mediators of the sympathoadrenal system, which is accompanied by desensitization of adrenergic receptors of erythrocyte cell membranes, the values erythrocyte membrane adrenoreactivity index (β-APM) increases, and adrenoreactivity decreases, and vice versa, with a decrease in the number of mediators, β-APM values decrease, and adrenoreactivity increases [9].

Evaluation of β-AWP is an early predictor of CHF progression in patients after MI, and it allows to identify a cohort of patients who have a high risk of progression of heart failure in the post-infarction period.

The technical result of the proposed invention is to improve the accuracy of prediction of the course of the disease, which allows you to:

- to assess the personal risk of progression of heart failure in patients within a year after MI;

- determine the priority group of patients with progression of heart failure after myocardial infarction for subsequent follow-up observation with the optimization of effective targeted personalized measures aimed at preventing the progression of heart failure.

The present invention can be used in healthcare to improve the accuracy of predicting the progression of heart failure in patients after MI.

Based on the foregoing, it should be considered that the invention meets the conditions of patentability "Novelty", "Inventive step", "Industrial applicability".

The invention will be clear from the following description and the attached figure.

In FIG. 1 presents the results of ROC analysis. The characterological curve (ROC-curve) of sensitivity and specificity of β-AWP values in the stratification of the risk of progression of heart failure during the year after MI is reflected. Specificity values (%) are plotted along the abscissa, and sensitivity (%) is plotted along the ordinates. According to the analysis, it follows that the “cut-off point” is cut off, which characterizes the prediction of the risk of progression of heart failure after transferred MI with a sensitivity of 92.3% with a specificity of 62.2% is the value of β-AWP≥49.53 el. (AUC - 0.71, p = 0.025).

The method is as follows:

In patients with CHF, 6 months after MI transferred from a cubital vein, blood is sampled into sterile vacuum systems in a volume of 2 ml containing an anticoagulant at the rate of 0.1 ml per 5.0 ml of blood in order to determine the beta-adrenoreactivity of red blood cells. For this purpose, a commercial set of the Agat-Med company “BETA-ARM AGAT” is used. Material used: whole blood.

1. 0.2 ml of whole blood with an anticoagulant is added to 0.2 ml of physiological saline, mixed, avoiding pricing. This sample is suitable for further processing for 3 hours at room temperature.

2. Reagents are added to centrifuge tubes according to the following scheme: two control and two experimental samples for each analyzed blood sample.

The supernatant is transferred to a photometer cuvette and the absorbance of the control samples is measured against physiological saline at a wavelength of 540 (500-560) nm in a cuvette with an absorbing light layer thickness of 10 mm or 5 mm.

3. The value of P-AWP is calculated by the formula:

where β-AWP is the value of the indicator of beta-adrenoreactivity of red blood cells, conventional units;

E01 and E02 - optical density of the experimental samples, unit opt. Density;

EK1 and EK2 - optical densities of control samples, unit opt.

The optical density in the control samples should be in the range of 0.4-1.3 units. opt. tight for cuvettes with a thickness of a light-absorbing layer of 10 mm (0.2-0.65 units of opt. density. for cuvettes with a thickness of a light-absorbing layer of 5 mm).

Statistical processing of the data obtained in the study was carried out using the STATISTICA 10.0 software and the demo version of SPSS Statistics 20.0. To analyze the quantitative data for compliance with the normal distribution law, the Shapiro-Wilk test was used. Quantitative data are presented as median and interquartile range (Me (Q25; 75)). To compare the quantitative data in two independent samples in the case of a distribution other than normal, the Mann-Whitney U-test was used. To determine the sensitivity and specificity of the beta-adrenergic reactivity indicator in stratification of the risk of progression of heart failure, ROC analysis was used. The critical level of significance in testing statistical hypotheses was taken equal to 0.05 (p-value - achieved significance level).

The study included 50 patients (40 men and 10 women) 6 months after myocardial infarction. The average age of men was 57.0 ± 11.5 years, the average age of women was 72.1 ± 10.2 years. At the time of inclusion in the study, all patients had heart failure of functional class I-III (FC) in accordance with the New York classification heart associations (NYHA, 1964) and received basic therapy for CHF - beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, mineralocorticoid receptor antagonists and, if necessary, diuretics.

After inclusion in the study, patients with CHF who underwent MI had a blood sampling followed by its analysis to determine beta-adrenoreactivity of red blood cells. Subsequently, patients were followed up for 6 months, after which an analysis was made of the frequency of onset of CHF progression (for 1 or more FCs according to NYHA according to the results of a 6-minute walk test). The clinical course of the disease was evaluated as favorable if during the entire study period of observation, against the background of adequately conducted therapy, the patient did not have progression of heart failure.

6 months after inclusion in the study, all examined patients were retrospectively divided into 2 groups in order to identify the possibility of associating the level of β-AWP with the development of progression of heart failure. The first group (group 1, n = 37) included patients with a stable course of heart failure, the second group (group 2, n = 13) included patients with progression of heart failure. The groups were comparable according to the main clinical and anamnestic indicators: according to the level of quality of life (determined by the European questionnaire for assessing the quality of life EQ-5D-3L), according to the characteristics of transferred MI (clinical picture, electrocardiogram data (presence of Q wave, ST segment elevation), presence complications in the acute period of myocardial infarction), according to the severity of coronary atherosclerosis (according to coronary angiography), but to the main indicators of the structural and functional state of the left ventricle (according to echocardiography), according to the presence of background pathology and frequency of administration of the main groups of drugs.

An analysis of beta-adrenoreactivity showed that in patients with progressive heart failure the level of β-AWP was 58.8 (50.9; 78.0) conventional units, which significantly exceeded the same indicator in patients with stable chronic heart failure (46.8 (38.0; 66.3) conventional units (p = 0.025)) (table 1).

According to the ROC analysis (Fig. 1), the “cut-off point” - cut off, characterizing the development of progression of heart failure during the year after MI, with a sensitivity of this criterion of 92.3% with a specificity of 62.2%, is the level of β-APM≥ 49.53 conventional units (AUC - 0.71, p = 0.025).

Thus, the indicator proposed in the invention demonstrated high predictive accuracy in assessing the probability of progression of heart failure in patients with MI, which allows us to recommend this method for stratifying the risk of progression of heart failure, as well as early personified diagnosis of this group of patients.

The proposed method for predicting the risk of progression of heart failure in patients after MI is illustrated by the following clinical examples, indicating that the detection of β-APM≥49.53 conv. is an important prognostic test for identifying patients at high risk of progression of heart failure within a year after MI.

Clinical example 1.

Patient K., male, 65 years old. In February 2017, he suffered an acute primary anterolateral Q-myocardial infarction with ST segment elevation. At the time of myocardial infarction, a typical clinical picture was observed. The post-infarction period was uneventful, anginal pain did not recur.

According to the results of coronary angiography: stenosis of the proximal segment of the right coronary artery (PKA) 40%; stenosis of the proximal segment of the anterior descending artery (PNA) 50% with calcification; stenosis of the middle PNA segment 75% with calcification; stenosis of the first branch of the obtuse margin (1BTC) 75%. According to echocardiography, the ejection fraction of the left ventricle (LVEF) is 38%>.

Clinical diagnosis: Main disease: CHD: acute primary anterolateral Q-myocardial infarction with ST segment elevation from 02/12/2017. Atherosclerosis of the coronary arteries: PKA - 40% in the proximal third, PNA - 50% in the proximal third and 75% in the middle third, 1BTC - 75%. Operation: Balloon dilation and stenting with the Xience Xpedition stent (drug-coated stent) - 3 × 48 mm of the proximal and middle segments of the PNA. Balloon dilatation and stenting with a Calypso stent (drug-coated stent) - 3 × 23 mm 1BTC. Background disease: Stage III hypertension, target BP level achieved. Atherosclerosis of the carotid (on both sides up to 10%) and femoral (on both sides up to 15%) arteries. Dyslipidemia. Chronic kidney disease C2 (GFR = 67 ml / min / 1.73 m ² ). Obesity 1 tbsp. Risk 4. Complications: Killip I. CHF IIA, FC II (NYHA).

Upon discharge from the hospital, the patient continued to be troubled by shortness of breath while walking about 300 meters, climbing stairs above 2 floors. The 6-minute walk test (TSH) was 320 meters. The patient was prescribed the following treatment for discharge: brilint 90 mg * 2 times a day, cardiomagnyl 75 mg 1 time per day, atorvastine 40 mg 1 time per day, bisoprolol 10 mg 1 time per day, lisinopril 10 mg 1 time per day, veroshpiron 50 mg 1 time per day, torasemide 10 mg 1 time per day.

6 months after myocardial infarction, the level of β-AWP in the blood was 60.81 conventional units. (> 49.53 conventional units), which allowed us to predict a high risk of an unfavorable course of the disease in the form of progression of heart failure. Indeed, 3 months after inclusion in the study, the patient experienced adequate progression of heart failure in the form of increased shortness of breath, weakness, and dyspnea when walking about 200 meters against the background of adequate therapy. The distance TShH was 180 meters (CHF III FC according to NYHA).

Clinical example 2.

Patient M., male, 60 years old. In March 2017, he suffered an acute primary anterolateral Q-myocardial infarction with an ST elevation. A heart attack was characterized by the presence of a typical clinical picture. The post-infarction period was uneventful, anginal pain did not recur.

According to the results of coronary angiography: stenotic atherosclerosis of the coronary arteries: PNA - occlusion in the proximal third, the first diagonal artery (1DA) - 50% stenosis in the proximal third, artery envelope (OA) - 30% stenosis in the proximal third. According to the results of echocardiography of LVEF, 39%.

Clinical diagnosis: Main disease: CHD: acute primary anterolateral Q-myocardial infarction with ST elevation from 03.15.17. Atherosclerosis of the coronary arteries: PNA - occlusion in the proximal third, 1DA - 50% in the proximal third, OA - 30% in the proximal third. Operation: balloon dilatation and stenting with the Xience Xpedition stent (drug-coated stent) - 3 × 23 mm of the proximal segment of the PNA. Background disease: Stage III hypertension, target BP level achieved. Dyslipidemia. Atherosclerosis of the carotid arteries (20%). Obesity of 1 degree. Type 2 diabetes mellitus, first detected, target glycated hemoglobin level <7.5%, glycated hemoglobin level 6.9% achieved. Chronic kidney disease C2 (GFR = 65 ml / min / 1.73 m ² ). Risk 4. Complications: Killip I. CHF ON, FC II (NYHA). Pulmonary venous hypertension of 1 degree. Pulmonary arterial hypertension of 1 degree. Blockade of the anteroposterior branch of the left leg of the bundle of His.

Upon discharge from the hospital, the patient was disturbed by shortness of breath when walking at a normal pace of about 400 meters. TShH amounted to 360 meters. The patient was prescribed the following treatment for discharge: cardiomagnyl 75 mg 1 time per day, plavix 75 mg 1 time per day, rosuvastatin 20 mg 1 time per day, metoprolol 25 mg 2 times per day, fosinopril 5 mg 1 time per day, veroshpiron 50 mg 1 time per day, torasemide 5 mg 1 time per day, siofor 850 mg 1 time per day.

6 months after myocardial infarction, the level of P-AWP in the blood of this patient was 26.78 conventional units. (<49.53 conventional units), which made it possible to predict the absence of progression of heart failure within a year after MI. Indeed, after 6 months of follow-up, the patient did not have a single case of progression of heart failure.

Clinical example 3.

Patient A., female, 68 years old. In January 2017, she suffered an acute primary anterior Q myocardial infarction with an ST segment elevation. Myocardial infarction proceeded with typical symptoms. The post-infarction period was uneventful, anginal pain did not recur.

According to the results of coronary angiography: PNA stenosis of 75% in the proximal third, OA stenosis of 50% in the proximal third, 1BTC stenosis of 30% in the middle third. According to the results of echocardiography - LVEF - 40%.

Clinical diagnosis: Main disease: coronary heart disease: acute primary anterior Q myocardial infarction with ST elevation from 01/28/17. Atherosclerosis of the coronary arteries: PNA - 75% in the proximal third, 1BTC - 30% in the middle third, OA - 50% in the proximal third. Operation: balloon dilatation and stenting with a Calypso stent (drug-eluting stent) - 3 × 23 mm of the proximal PNA segment. Background disease: Stage III hypertension, target BP level achieved. Atherosclerosis of the carotid arteries (20% on both sides), atherosclerosis of the femoral arteries (10% on both sides). Obesity 2 tbsp. Violation of tolerance to carbohydrates. Chronic kidney disease C2 (GFR = 60 ml / min / 1.73 m ² ). Risk 4. Complications: Killip I. CHF IIA, FC II (NYHA).

Upon discharge from the hospital, the patient was still worried about shortness of breath arising from walking 300-350 meters. TShH amounted to 330 meters. The patient was prescribed the following treatment for discharge: cardiomagnyl 75 mg 1 time per day, plavix 75 mg 1 time per day, atorvastatin 40 mg 1 time per day, metoprolol 25 mg 2 times per day, lisinopril 10 mg 1 time per day, veroshpiron 50 mg 1 time per day, torasemide 10 mg 1 time per day.

6 months after myocardial infarction, the level of the indicator (β-AWP in the blood was 49.53 conventional units, which made it possible to predict a high risk of an unfavorable course of the disease in the form of progression of heart failure. Indeed, 3 months after inclusion in the study, the patient had adequate of the treatment, progression of CHF was observed in the form of increased shortness of breath, weakness, and shortness of breath when walking 150-200 meters.The distance TLC was 175 meters (CHF III FC according to NYHA).

Using the presented clinical cases as an example, it has been convincingly demonstrated that the level of β-APM ≥49.53 conv.ed. has prognostic value in relation to predicting the progression of heart failure within a year after MI.

Proposed as an invention, the method was tested on 50 patients with heart failure and transferred myocardial infarction and allows to predict the risk of progression of heart failure within one year after myocardial infarction. which contributes to the identification of a priority group of patients with increased risk for more intensive follow-up with the organization of effective personalized events and the implementation of reasonable pathogenetic therapy aimed at preventing the development of progression of heart failure, which will prevent high premature mortality in this category of patients.

LIST OF REFERENCES

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Claims (1)

A method for predicting the progression of chronic heart failure within a year after a myocardial infarction, characterized in that a patient is sampled 6 months after a myocardial infarction and the erythrocyte beta-adrenoreactivity is determined, and if the erythrocyte adrenoreactivity index values are determined, β-APM is greater than or equal to 49.53 conventional units predict the progression of chronic heart failure, and if β-AWP values are detected below 49.53 arb. predict a favorable course of the disease.

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