RU2220421C2 - Method for predicting instable stenocardia and finely local myocardial infarction - Google Patents

Abstract

FIELD: medicine, cardiology. SUBSTANCE: one should carry out periodical patient's blood sampling during a day, prepare samples of blood serum, detect values for myoglobin concentration in these samples due to radioimmune assay and fix them in dynamics, choose valuable myoglobin concentration values to compare them against a control and conclude upon availability and type of pathology, moreover, blood sampling, preparation of samples and successively above-mentioned procedures should be carried out immediately after patient's entering medicinal establishment for the first time, at their further periodical repetition for the first 6 h to conclude upon availability of instable stenocardia at keeping myoglobin concentration values ranged 80-200 ng/ml for the first 6 h, and for predicting MI one should continue the above- mentioned procedures for the first day and at keeping concentration values ranged 150-300 ng/ml during the first day it is possible to conclude upon availability of IM. EFFECT: higher objectivity and accuracy of diagnostics. 2 ex

Description

 The invention relates to medicine, namely to cardiology, and can be used in the differential diagnosis of unstable angina and small focal (without Q wave) myocardial infarction (MI) in patients with a cardiological profile, as well as the corresponding correction of a complex of therapeutic and rehabilitation measures in a hospital and post-hospital periods.

 Known methods for the diagnosis of unstable angina [1, 2, 3, 4, 5]. Unstable angina pectoris is a period of exacerbation of coronary heart disease, characterized by a high risk of developing large focal myocardial infarction and expressed in a qualitative change in angina attacks, primarily in the appearance of rest angina. Outside of pain attacks in this period, for a day or more, changes in the final part of the ventricular ECG complex are noted [1].

 The identification of unstable angina as a special condition is caused by the need to develop organizational and therapeutic measures that could, if not prevent the development of MI, at least make its course more favorable, as well as reduce the frequency of sudden death.

 There is also known a method for the diagnosis of angina pectoris [2], based on the analysis of patient complaints, the intensity and duration of anginal pain, their irradiation, communication with physical activity observed during an attack of myocardial ischemia. The main one listed for the diagnosis of unstable angina is a change in the nature of the attacks. Therefore, the condition of a patient in whom angina attacks are rare (1 time in 6-7 days) is recognized as unstable, if they differ from those that had previously or appeared for the first time in life and if a change in the end of the ventricular complex on the ECG is noted in the interictal period.

 The disadvantages of this method is the subjectivity of the patient’s assessment of their feelings and, as a result, the insufficient objectivity of the data obtained.

 An electrocardiographic method for diagnosing angina pectoris is also known [3], which consists in recording electrical potentials from the patient’s body surface, using signs indicating impaired electrophysiological and metabolic processes in areas of insufficient myocardial blood supply as objective criteria for myocardial ischemia.

 The disadvantage of this method is bias, since these changes are short-term, the frequency of their detection is low. In addition, due to the integrated nature of the reflection of the bioelectric activity of myocardial cells, difficulties in interpreting changes in the final part of the ventricular complex on the ECG in patients with hypertension, especially those with ECG signs of LV hypertrophy, do not allow to differentiate ischemia from damage and objectify this separation quite clearly.

 Also known is a scintigraphic method for the diagnosis of myocardial ischemia in angina pectoris [4], which consists in the intravenous administration of a radioactive indicator 201T1 (or its analogues) and an assessment of its accumulation and redistribution in the heart muscle.

 The disadvantages of this method are: the dependence of the detected perfusion defects on the localization of coronary stenosis, the degree and number of atherosclerotic stenotic coronary arteries; radiation load on the patient, limiting the frequency of studies in dynamics; the need to use a specialized expensive detection device - gamma camera.

 In addition, the disadvantages of these methods, with all their positive features, is the inability to do with one common technique for distinguishing patients by type of disease. This leads to a delay in the start of targeted treatment, to a rise in the cost of the research process, to the appointment of invasive procedures unnecessarily.

Therefore, two should be cited as the closest analogue:
- one as a way to diagnose unstable angina,
- another as a way to diagnose myocardial infarction.

 The closest way to diagnose unstable angina to the claimed technical solution is the method [5], which consists in analyzing the dynamics of serum myoglobin (Mg) after a stress test and before it. The essence of this method is to take the patient’s blood samples before and after performing a load test after 6, 12 and 24 hours, conducting a radioimmunoassay and measuring the concentration of serum myoglobin, evaluating the data obtained with fixing values of more than 80 ng / ml. Moreover, as a sample, bicycle ergometry is chosen. The method allows for the differential diagnosis of stable and unstable forms of angina pectoris.

 The disadvantages of this method is the fact that it can only be used if the patient is stabilized, but not for the differential diagnosis of unstable angina and small focal myocardial infarction in the acute period (first day) due to the presence of direct contraindications for VEM testing in this period.

 The closest analogue to the method for diagnosing MI is [6]. The essence of this method is to take the patient’s blood during the day, prepare blood serum samples, conduct a radioimmunoassay of the content of myoglobin in the patient’s blood serum, determine the concentration of myoglobin, fix them in dynamics and compare with the control. Moreover, the concentration of 54.25 ± 2.2 ng / ml (from 40 to 87 ng / ml) is taken as the control value of healthy individuals, and the average level of Mg concentration in patients with MI on the first day is 1027.7 ± 53.9 ng / ml

 The disadvantages of this method is that it is used in the late (more than six hours from the onset of acute coronary insufficiency) stages of the disease and therefore does not allow to differentiate unstable angina from small focal MI.

 The task of the invention is to increase the objectivity and accuracy of determining the pathology and its type: unstable angina pectoris or myocardial infarction while simplifying the method and observing the safety of the patient during the study.

 The essence of the invention lies in the fact that in the method for the diagnosis of unstable angina and small focal myocardial infarction, in which the patient’s blood sampling is periodically repeated during the day, blood serum samples are prepared, the concentration of myoglobin in them is determined by the radio-immune method and they are fixed in dynamics, choose from the obtained significant values of the concentration of myoglobin and compare them with the control, which judge the presence and type of pathology, while blood sampling, preparation of samples and sequentially others The above procedures are carried out immediately after the patient enters the medical institution for the first time, followed by periodic repetition of them during the first six hours and the presence of unstable angina is maintained while maintaining myoglobin concentrations in the range from 80 to 200 ng / ml for the first six hours, and for the diagnosis of myocardial infarction, the above procedures are continued during the first day, and while maintaining concentration values from 150 to 300 ng / ml during the day, the presence of myocardial infarction is judged.

 The inventive method is as follows: prepare a series of reaction tubes from the calculation: two tubes to determine the total introduced activity, twelve tubes - to build a calibration curve and two tubes for each analyzed serum.

 20 μl of myoglobin standards are added to calibration tubes, containing respectively: 0; 9.5; 47.5; 143; 475; 1140 ng / ml, and in experimental - 20 μl of patient sera.

 300 μl of labeled 125I-Mg are added to all tubes.

 Mix the contents of the tubes with a vortex mixer for 3-5 seconds. The tubes are incubated for 60 minutes at room temperature and continuously shaken (280 rpm) on a horizontal shaker.

 At the end of the incubation, the contents of all tubes are carefully removed using a water-jet pump, except for those intended to measure total activity.

 The count rate of the radionuclide 125-I in each pair on the gamma counter is determined. Counting time is one minute.

 The arithmetic mean of the count rate of the radionuclide in each pair of tubes is calculated: with the total activity introduced, with calibration and analyzed samples.

 A calibration curve is built in linear coordinates, defining the Mg concentration along the abscissa axis, and the corresponding average count rate along the ordinate axis. Through the points obtained, a smooth curve is drawn.

 The myoglobin content in the analyzed blood samples is determined. For this, the arithmetic average of the count rate of the radionuclide in test tubes containing patient samples is plotted along the ordinate axis. Through the obtained point, draw a straight line parallel to the abscissa axis, until it intersects with the calibration curve. The perpendicular is lowered from the intersection point to the intersection with the abscissa axis, where the Mg value in the analyzed samples is determined. Similarly, the content of myoglobin in the remaining samples is determined.

 After determining the concentrations of myoglobin, an analysis of the obtained data is performed. At the same time, the presence of unstable angina is judged while maintaining the concentration of myoglobin in the range from 80 to 200 ng / ml for the first six hours, and the preservation of the concentration of Mg during the day in the range from 150 to 300 ng / ml indicates the presence of small focal MI.

 For clinical verification of the proposed method, 255 patients were examined from 28 to 65 years old (average age 49.4 ± 0.8 years), 150 people with a diagnosis of angina pectoris, 50 with a diagnosis of small focal myocardial infarction, 26 with cardiac neurocirculatory dystonia, 16 with hypertension of stage 2 and 13 with osteochondrosis of the cervicothoracic spine with radicular manifestations and pain in the heart.

To solve the tasks, the study included patients with exacerbation of angina pectoris who met the following criteria:
1. The presence of a pain attack that required the introduction of analgesics, which made AMI suspected.

 2. The appearance of angina pectoris or angina of rest for the first time in life.

 3. Change in the nature of angina attacks in the form of an increase in their intensity, duration, decrease or disappearance of the reaction to nitroglycerin intake and / or an increase (more than 2-fold) in the number of angina attacks without changing their nature.

 Symptoms of the changed nature of the disease appeared within 1-4 weeks prior to hospitalization. For comparison, patients with chronic stable angina were examined with an increase in the number of angina attacks by less than 2 times. The control group of patients with functional pathology, which was necessary to differentiate with SC, allowed us to determine the sensitivity and specificity indicators in relation to coronary angiography and biochemical techniques.

 Duration of the disease up to 1 year was observed in 15% of the examined, the rest had a longer history. Myocardial infarction in the past suffered 75 (or 36.6%) of the examined. In the majority of patients, myocardial infarction was intramural, and only 29 of the examined had cicatricial changes, Q wave on the ECG, indicating a large focal myocardial infarction in the past. The most common concomitant illness was hypertension (GB). Its frequency was 55%. Changes in the spine were frequent - osteochondrosis was noted in 57% of patients. Chronic bronchitis (in 23 cases), peptic ulcer of the stomach and 12 duodenal ulcer (18 patients), chronic cholecystitis (14 cases) and thyrotoxicosis (in one).

 No new ECG changes were observed among the examined patients during hospitalization, and the existing ST-T changes were “nonspecific”.

 Along with the traditional survey, an anamnesis based on a formalized questionnaire developed by E. Sh. determination of blood cholesterol and triglycerides, fibrinogen, prothrombin, blood glucose, creatinine and b2-microglobulin in blood serum and urine. To obtain biochemical confirmation of ischemic myocardial damage, all patients underwent serial determination of serum myoglobin level, blood enzyme activity (creatine phosphokinase, MB fraction of creatine phosphokinase, lactate dehydrogenase, hydroxybutyrate dehydrogenase, aspartate transferase).

 Hypercholesterolemia and b-lipoproteinemia were observed in 55% of patients, fibrinogen level was increased in 41% of cases, which was a condition for increased thrombosis in NSC. Renal pathology was excluded, which could affect the slower elimination of protein markers of myocardial necrosis, in particular MG. For this purpose, the level of b2-microglobulin in blood serum and urine was determined (in no case should it exceed the upper limits of the norm - 2.4 μg / l in blood and 0.05 mg / l in urine.

 Statistical data processing was carried out on a PC XT 486 computer using the MED.STAT application package. For data processing, methods of variation statistics were used. For a comparative analysis, we used the methods of criteria for agreement x, correlation analysis. Significance of differences was determined by student t-test.

 Reference values of the MG level in control group individuals (neurocirculatory dystonia, cardialgia) were clarified. They amounted to 37.4 ± 1.7 ng / ml (with a range of fluctuations from 9.1 to 65.8 ng / ml). With stable angina pectoris, repeated blood sampling at the time of the onset of the attack and in dynamics did not reveal significant differences in the level of MG from the control group, it amounted to 44.3 ± 4.5 ng / ml.

 The study of changes in the level of MG in patients with NSC revealed its mandatory increase above 80 ng / ml, which is not characteristic of stable angina, averaging 136.2 ± 9.2 ng / ml (range from 80 to 200 ng / ml). Among patients with NSC, with an increase in the duration and intensity of the pain syndrome, a single determination of the MG level made it possible to detect a moderately pronounced transient hypermyoglobinemia with a 90% probability. Dynamic determination of the level of MG blood allows to identify peaks of hypermyoglobinemia in almost all patients in the acute period of NSC. In the group of patients with small focal MI, the Mg concentration averaged 208.3 ± 15.1 ng / ml (range from 150 to 300 ng / ml).

 Parallel MG determination of the activity of a number of enzymes showed a lower sensitivity. The activities of LDH, ACT, and CPK, which changed in 35% of cases, did not go beyond the boundaries of the "gray zone". The increase in the activity of highly specific for myocardial tissue MV-CPK was accompanied by hypermyoglobinemia, but was also less pronounced, the peak of its activity was observed at the 12th hour of the study. The sensitivity of Mg was significantly higher than previously considered methods and reached 90%.

 Examples of specific applications of the proposed method.

 Example 1. Patient T. V. I., 55 years old. Medical history N13923. He was admitted to the hospital at the time of an attack of acute coronary insufficiency with complaints of a burning sensation behind the sternum on the background of a psychoemotional load lasting 15 minutes, which were stopped by intramuscular injection of narcotic analgesics. I am ill with coronary artery disease angina pectoris II functional class for 2 years. Exacerbation of the disease took place within two days before hospitalization. The aggravation was manifested in an increase in angina attacks, a change in the causes of pain (they began to occur when walking on flat terrain up to 200 meters, at rest). The attacks have become more protracted. So, if in the previous time the duration of an angina attack did not exceed 5 minutes and the pain was quickly stopped by taking nitroglycerin, now the duration of an anginal attack has increased to 15 minutes. The pain is poorly stopped by taking nitroglycerin, leaving behind a "residual" pain of a dull nature. On the ECG: sinus rhythm - 85 per minute. The electrical axis of the heart is 30. Changes in the T wave in leads V5-V6. The ST segment is on the isoline. Biochemical studies: CPK 205 u / l. Cholesterol 188 mg / dl. White blood cells 6.3 • 10 • 6. ESR 7 mm / h. When examining the proposed method: Mg concentration was 140, 180, 125, 175, 64, 80 ng / ml, respectively. The diagnosis was made: coronary heart disease unstable angina pectoris. When observed in the dynamics and treatment, the patient's condition stabilized and began to correspond to the clinical picture of angina pectoris II functional class.

 Thus, the application of the proposed method made it possible to diagnose the unstable nature of angina pectoris on the basis of changes in the clinical picture and changes in Mg concentrations during the first 6 hours of hospitalization, indicating a violation of the integrity of the membranes of cardiomyocytes that did not reach the values and the duration of the increase in concentrations characteristic of MI. This was also confirmed by the absence of ECG changes characteristic of non-transmural MI, as well as the rapid stabilization of the patient's clinical condition.

 Example 2. Patient F.V.K., 39 years old. Received complaints of pain behind the sternum of an intense nature. Deterioration of the condition is observed during the month preceding hospitalization in the clinic, when pain began to be noted at rest, with emotional stress, their intensity and duration increased. After the last psycho-emotional stress at work, after 2 hours he was delivered to the clinic with complaints of: pain behind the sternum of a pressing nature, lasting up to 15 minutes, arising with slight physical exertion, not stopping with nitroglycerin. On an ECG: sinus rhythm, 80 per minute. The electrical axis of the heart is horizontal, signs of left ventricular hypertrophy. Changes in the ST segment and the T wave are not observed. Biochemical studies: CPK 215 u / L. Cholesterol 209 mg / dl. White blood cells 6.6 • 10 • 6. ESR 4 mm / h. When examining the proposed method: Mg concentration was 80, 110, 130, 181, 230, 160 ng / ml, respectively. The diagnosis was made: ischemic heart disease, small focal (not Q) myocardial infarction. The diagnosis is confirmed by changes in the ECG that appeared in a subsequent period. T wave became negative in leads III, aVF, V5-V6, up to 3 mm deep, symmetrical; as well as changes in the ESR reaction, the appearance of leukocytosis, indicating the presence of resorption-necrotic syndrome.

 Thus, the initial clinical picture and ECG changes did not allow to differentiate these two cases in the first 3 days from the time of hospitalization. And only the application of the proposed method allowed to clearly distinguish between these conditions.

Sources of information
1. Graziansky N.A. Unstable angina pectoris. Diagnosis, clinical options, treatment principles. / Guidelines. M., 1988, 19 p.

 2. Angina pectoris / Ed. D. Juliana. M., Medicine, 1980, p. 53-95.

 3. Goldhammer S., Schef D. Electrokardiographische untersuchungen bei kranker mit angina pectoris ("ambulatotischer typus"). - Leit-schrift fur Klinische medizin., 1933, 122-134.

 4. Lishmanov Yu.B., Chernov V.I. Myocardial scintigraphy in nuclear cardiology. Tomsk, Publishing House Tom. Un-a, 1997, p. 140-186.

 5. Podzemelnikov E.V., Bebeshko S.Ya. A method for the diagnosis of stable and unstable forms of angina pectoris. RU 2111697. Bull. Patents of the Russian Federation, 1998; fifteen.

 6. Ivanov S.G., Orlov V.N., Bulgakov S.A. Determining the concentration of myoglobin in the blood is a method of early diagnosis of myocardial infarction. Therapeutic Archive, 1981, N4, pp. 11-12.

Claims (1)

A method for the diagnosis of unstable angina and small-focal myocardial infarction (MI), in which the patient’s blood sampling is periodically repeated during the day, blood serum samples are prepared, the concentration of myoglobin in them is determined by the radio-immune method and recorded in dynamics, significant values of the concentration of myoglobin are selected from the resultant and compare them with the control, which judge the presence and type of pathology, characterized in that the blood sampling, preparation of samples and sequentially the other above mentioned procedures they are tested immediately after the patient’s admission to a medical institution for the first time, followed by periodic repetition of them during the first six hours and they are judged on the presence of unstable angina while maintaining myoglobin concentrations in the range from 80 to 200 ng / ml for the first six hours, and for diagnosis MI continue the above procedures during the first day and while maintaining concentration values from 150 to 300 ng / ml during the day they judge the presence of MI.