RU2195179C2 - Method for diagnostics of viable myocardium - Google Patents

Abstract

FIELD: medicine, cardiology, cardiosurgery. SUBSTANCE: patient with ischemic cardiac disease undergoes an ultrasound testing to evaluate regional contractility of left ventricle. Repeated ultrasound testing for evaluating regional contractility of left ventricle is carried out 2 h later after a single peroral intake of 60 mg trimetazidine (preductal 20, vastarel). In case of viable myocardium one should obtain improved regional contractility at the background of medicinal preparation in departments with initially decreased contractility. EFFECT: higher accuracy of diagnostics. 3 ex, 1 tbl

Description

 The proposed development relates to the field of medicine and relates to cardiology and cardiac surgery.

 A known method for the diagnosis of viable myocardium in patients with coronary heart disease [1], which use dobutamine (dobutrex), a synthetic catecholamine that increases heart rate, increases blood pressure and myocardial contractility. Two schemes (protocols) of stress echocardiography are used: 1) using small doses administered intravenously with a dispenser from 2.5 or 5 to 10 or 20 μg / kg / min for 3 minutes, followed by a comparison of local contractility with the original data; 2) followed by the introduction of high doses of dobutamine (up to 40 μg / kg / min), followed by a comparison of local contractility with baseline data. The first protocol of this study allows us to identify an improvement in the initially impaired local contractility, with the subsequent administration of high doses of the drug (the second protocol), the contractility of the sites deteriorates both improving contractility at low doses of the drug and others that do not increase contractility against the background of small doses of dobutamine. The sensitivity of the dobutamine test in relation to a viable myocardium at a dose of 5 μg / kg / min for 3 minutes, followed by an increase to 10 μg / kg / min for 3 minutes, was 72% (95% confidence interval from 60.9 % to 81.3%), specificity 92% (95% confidence interval from 82.4% to 97.3%) [2]. According to other authors, when using initial doses of dobutamine 5 μg / kg / min for 3 minutes with a subsequent increase in dose to 10, 15, 20, 30 and 40 μg / kg / min, the sensitivity was 98%, specificity 91% [ 3].

 The disadvantage of this method is the presence of a large number of contraindications: hemodynamically significant obstruction to the outflow from the left ventricle, hemodynamically significant valvular heart defects, predisposition or anamnestic indications of clinically significant or chronic arrhythmias, congestive heart failure (III - IY class according to NYHA), significant cardiac conduction disorders recently suffered (up to 30 days) myocardial infarction, unstable angina, high arterial hypertension, anamnestic indications of hemorrhage cal stroke, aortic aneurysm, history data on hypertensive response to dobutamine or its analogs. Stress is not recommended for patients with significant electrolyte abnormalities (hypokalemia, hypomagnesemia), with a significantly longer ECT QT interval, with dilated cardiomyopathy or cardiografts, with closed-angle form of glaucoma, uncompensated hyperthyroidism, taking antiarrhythmic drugs class I and antiarrhythmic drugs (1) 3 classes (amiodarone, cordarone), consuming atropine (or other anticholinergics), digoxin, tricyclic antidepressants. Another disadvantage of this method is the need for intravenous infestation, the presence of a dispenser, constant monitoring of blood pressure, heart rate, ECG, the participation of at least 2 doctors who are ready to provide resuscitation. Subjectively examined often noted tremor, headache, flushing, dizziness, paresthesia, nausea, feeling of heat, dry mouth. A sufficient number of complications during the test (first of all, an excessive hypertonic reaction, the appearance of various types of rhythm disturbances, provocation of angina pectoris up to myocardial infarction), as well as the relatively high cost of dobutamine, limit its distribution in medical institutions of our country. Although with small doses of dobutamine (protocol 1), the risk of complications is reduced.

 A known method for the diagnosis of a viable myocardium with enoximon, which is a non-glycoside and nonsympathomimetic drug with a positive inotropic effect that does not affect heart rate and blood pressure and is an inhibitor of phosphodiesterase III; the drug realizes its inotropic effect due to an increase in CAMP inside the cell. Enoximon is administered intravenously by a bolus at a dose of 1 mg / kg for 5 minutes under echocardiographic control before, during and 10 minutes after the dose. The sensitivity of the sample in patients with LV ejection fraction less than 40% was 93%, specificity - 92% [4]. There are significantly fewer complications compared to the dobutamine breakdown. The disadvantages of this method include invasiveness, and most importantly, the low prevalence of this drug in the pharmacy network and its high cost.

 Also known is a method for diagnosing a viable myocardium using low physical activity. It is based on an increase in the concentration of endogenous catecholamines under the influence of low physical exertion and their effect on a viable myocardium, which leads to an improvement in initially impaired local contractility. Dosed physical activity is performed on a bicycle ergometer (VEM) in a vertical position with an initial power of 25 W and increasing it by 25 W every three minutes. After the first stage or increase in heart rate by 10-20 beats / min, ultrasound data is recorded in the sitting position, also at the end of the test at peak load or in the first minute of rest in a horizontal position. The sensitivity and specificity of the sample were 83% and 76%, respectively, positive predictive accuracy - 83%, negative predictive accuracy - 76% [3].

 The disadvantage of this method is the additional use of a bicycle ergometer, constant heart rate and blood pressure control, the participation of at least two doctors, the deterioration in the quality of ultrasound examination due to increased respiratory excursion of the chest, narrowing of the ultrasound window.

 Closest to the proposed method is a method for the diagnosis of viable myocardium in patients with coronary heart disease using stress echocardiography with low doses of dipyridamole (chimes, persantine) to identify a viable myocardium. An increase in the contractility of a viable myocardium under the influence of small doses of dipyridamole is realized due to two possible mechanisms: hemodynamic (due to an increase in perfusion in the region) or metabolic, associated with the accumulation of endogenous adenosine and leading to an increase in contractility of a viable myocardium regardless of the degree of perfusion due to blockade of slow calcium channels ( with a decrease in calcium in the cytoplasm), stimulation of glycolysis, suppression of the formation of free radicals. Dipyridamole, diluted with saline, is administered intravenously at a dose of 0.28 mg / kg for 4 minutes. An echocardiographic examination is carried out before, during and after the administration of the entire dose. By comparing the initial and obtained data, a conclusion is made about the presence or absence of a viable myocardium. The sensitivity of the method was 67% (confidence interval from 55.8% to 77%), specificity - 95% (confidence interval from 86.7% to 99%), diagnostic accuracy - 79% [2]. With another method of administering dipyridamole intravenously in small doses of 0.26 mg / kg for 2 minutes and comparing the initial and obtained data, the sensitivity to viable myocardium was 97%, specificity 91%, positive predictive accuracy 96%, negative - 91% [3].

 The disadvantages of the method is the effect of the drug on the cardiovascular system: a decrease in systemic blood pressure, an increase in heart rate, provocation of rhythm and angina; subjectively examined noted headache, dizziness, flushing, pulsation of the vessels of the head, nausea, asthma attacks. Contraindications to the dipyridamole test: an allergic reaction to dipyridamole in the anamnesis, obstructive respiratory diseases, the presence of severe LV myocardial hypertrophy. Another disadvantage of this method is its invasiveness, the need for continuous monitoring of blood pressure, heart rate, ECG, the presence of at least two doctors.

 The essence of the development lies in the fact that in the diagnosis of viable myocardium in patients with coronary heart disease, based on the improvement of initially impaired local contractility under the influence of a drug that affects the contractility of viable myocardium, with preliminary and subsequent ultrasound examination of the heart to detect changes in impaired local contractility, as a drug that affects the contractility of a viable myocardium, a tablet form of the trimetazi cytoprotector is used ins (preduktal 20 vastarel) in a single oral daily dose and subsequent ultrasonic assessment local contractility at the height of the drug concentration in blood.

 The proposed method for the diagnosis of viable myocardium in patients with coronary heart disease is implemented as follows.

 Initially, the patient undergoes an ultrasound examination of the heart with a segmental assessment of contractility, 60 milligrams of trimetazidine (preductal 20, vastarel) are given orally once, and then after two hours a second ultrasound examination is performed. By comparing the initial and obtained data, a conclusion is made about the presence or absence of a viable myocardium. The use of video enhances diagnostic value.

 Example 1. Patient M., 51 years old. Diagnosis: ischemic heart disease. Angina pectoris III functional class. Post-infarction cardiosclerosis (Q-myocardial infarction from 10.21.98). NK IIA. Coronary angiography was performed and is preparing for surgical treatment of coronary artery disease. To solve the question of the feasibility of surgical treatment, a test with dipyridamole was conducted to determine a viable myocardium. Initially, akinetic segments were identified - 6, hypokinetic - 4, normokinetic - 6. The index of violation of local contractility (INLS) was 2.00. After intravenous administration of dipyridamole at a dose of 0.28 mg / kg for 4 minutes, the following were revealed: akinetic segments - 6, hypokinetic - 1, normokinetic - 9; INLS was 1.81. The next day, the patient was given once 60 mg of trimetazidine and after 2 hours an ultrasound examination was performed. Its results: akinetic segments - 5, hypokinetic - 2, normokinetic - 9; INLS was 1.75. Thus, an improvement in local contractility occurred in both cases, but when using the preductal, a viable segment from previously akinetic in previous studies was revealed (it became hypokinetic).

 Example 2. Patient M., 58 years old. Diagnosis: ischemic heart disease. Angina pectoris III functional class. Post-infarction cardiosclerosis (Q-myocardial infarction from 10.01.99). Ventricular extrasystole of the II gradation (on Laun). Hypertension stage II, moderate. NK IIA. Coronary angiography was performed and is preparing for surgical treatment of coronary artery disease. To solve the question of the feasibility of surgical treatment, a test with dipyridamole was conducted to determine a viable myocardium. Initially, akinetic segments were identified - 6, hypokinetic - 3, normokinetic - 7. The index of violation of local contractility (INLS) was 1.937. After intravenous administration of dipyridamole at a dose of 0.28 mg / kg for 4 minutes, the following were revealed: akinetic segments - 3, hypokinetic - 5, normokinetic - 8; INLS was 1.6875. The next day, the patient was given once 60 mg of trimetazidine and after 2 hours an ultrasound examination was performed. Its results: akinetic segments - 2, hypokinetic - 2, normokinetic - 14; INLS was 1.5. Thus, an improvement in local contractility occurred in both cases, but the use of a preductal revealed a viable segment from previously akinetic (including breakdown with dipyridamole) and a decrease in hypokinetic segments due to their normokinesia (compared with the initial and dipyridamole data).

 Example 3. Patient L, 51 years old. Diagnosis: ischemic heart disease. Angina pectoris III functional class. Post-infarction cardiosclerosis (Q-myocardial infarction from 04/13/99). NK IIA. Coronary angiography was performed and is preparing for surgical treatment of coronary artery disease. To solve the question of the feasibility of surgical treatment, a test with dipyridamole was conducted to determine a viable myocardium. Initially, akinetic segments were identified - 3, hypokinetic - 3, normokinetic - 10. The index of the violation of local contractility (INLS) was 1.5625. After intravenous administration of dipyridamole at a dose of 0.28 mg / kg for 4 minutes, the following were revealed: akinetic segments - 2, hypokinetic - 3, normokinetic - 11; INLS was 1.4375. The next day, the patient was given once 60 mg of trimetazidine and after 2 hours an ultrasound examination was performed. Its results: akinetic segments - 2, hypokinetic - 2, normokinetic - 12; INLS was 1.375. Thus, an improvement in local contractility occurred in both cases, but compared with the dipyridamole test, an additional improvement was due to the transition of the hypokinetic segment to normokinetic.

 The authors compared the data of 10 patients who successively conducted dipyridamole and acute trimetazidine tests for a viable myocardium. In one case with a dipyridamole test, ischemia was provoked (including clinical and ECG data) with an increase in INLS from 1.8125 to 2.1875 (i.e., the absence of a viable myocardium), in this patient an acute trimetazidine test also did not reveal the presence of a viable myocardium (INLS remained former), but without provocation of ischemia (including clinical and ECG data). According to the survey results, the data presented in table. 1 (average value, average deviation, significance of differences).

Compared with the dipyridamole test at a dose of 0.28 mg / kg for 4 minutes to determine a viable myocardium in relation to the acute test with trimetazidine (a single oral administration of trimetazidine at a dose of 60 mg followed by examination after 2 hours), the following data were obtained:
Sensitivity 100%
100% specificity
Predictive value of a positive test 100%
Predictive value of negative test 100%
Diagnostic accuracy 100%
Naturally, these data will be adjusted with an increase in the number of examined patients.

 Thus, the use of a single oral dose of 60 mg trimetazidine is as effective in determining viable myocardium in patients with coronary heart disease, as is the test with dipyridamole at a dose of 0.28 mg / kg intravenously for 4 minutes.

 Non-invasiveness, ease of implementation and low cost are the advantage and advantage of the proposed method compared to the analogue.

Literature
1. Alekhin M.N., Sedov V.P., Sidorenko B.A. "The possibilities of stress echocardiography in detecting a viable myocardium." Journal of Cardiology 1999, 2, p. 86-91.

 2. Picano E., Ostojic M., Varga A., Sicari R., Djordevic-Dikic A., Nedeljkovic I., Torres M. Combined low dose dipyridamol-dobutamine stress-echocardiography to identify myocardial viability. JACC Vol. 27, No 6. May 1996: 1422-8.

 3. Buziashvili Yu. I., Asymbekova E.U., Matskeplishvili S.T. "Diagnosis of reversible myocardial dysfunction in patients with coronary heart disease according to stress echocardiography." Journal of Thoracic and Cardiovascular Surgery 1999, 6, p. 68-80.

 4. Carlino M., Chierchia S., Lu C. et al. Enoximon echocardiograghy for identification of viable myocardium in patients with ischemic ventricular dysfunction: comparsion with dobutamine echocardiograghy and positron emission tomography. J Am Coil Cardiol 1997; 29: Suppl A: 917.

Claims (1)

 A method for diagnosing a viable myocardium, including ultrasound examination before and after drug administration, and characterized in that the drug is an oral cytoprotector trimetazidine (preductal 20, vararel) in a single dose of 60 mg, followed by ultrasound at a height of the concentration of the drug in the blood .

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