RU2398507C1 - Method of predicting degree of risk of restenosis development in coronary stent - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to cardiology and can be used to predict degree of restenosis development in coronary stent. For this purpose rate of nitrogen-containing preparation metabolism is determined by introduction the preparation into the test. As test-preparation introduced is caffeine in dose 150-300 mg orally once. After 6 hours ratio of N-acetyl-derivative of the preparation to non-metabolised preparation in urine is determined. If value of said ratio equals 73 % and lower favourable outcome of stenting is predicted.

EFFECT: said procedure ensures increase of accuracy in predicting degree of risk of restenosis development in coronary stent.

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Description

The invention relates to medicine, namely to cardiology, and can be used to predict the degree of risk of developing restenosis in the coronary stent.

A known method for predicting the development of restenosis based on clinical or anatomical parameters (1 - Hirshfeld J.W. Jr. et al., 1991). This method is taken as an analog.

There is a method for predicting the risk of developing restenosis in the coronary stent, adopted as a prototype, according to which, when GP IIb / IIIA platelet receptor glycoprotein receptor blockers are not used, fatal restenosis often develops, myocardial infarction; the use of GP IIb / IIIA platelet glycoprotein receptor blockers increases the reliability of predicting a favorable stenting outcome (2 - Osiev A.G., Grazhdankin I.O., 2008). However, the known method does not have sufficient accuracy.

The aim of the present invention is to improve the accuracy of predicting the degree of risk of developing restenosis in the coronary stent.

The technical result is achieved in that the metabolic rate of the nitrogen-containing compound is determined by the acetylator, by which the outcome of stenting is judged.

The technical result is also achieved by the fact that caffeine in a dose of 150-300 mg is used as a test preparation, the ratio of the N-acetyl derivative and the non-metabolized nitrogen-containing compound is determined and a favorable stenting outcome is predicted with a ratio of 73% or less.

The method is as follows.

Upon admission, patients with coronary heart disease complain of pain in the heart region with characteristic irradiation.

During examination, patients were diagnosed with stable angina of the I-III functional class.

An angiographic study revealed de novo stenoses of type A-B1, excluding damage to the trunk of the left coronary artery, osteal localization, and the proximal segment of the anterior interventricular branch. The reference diameter of the artery in the lesion is 4 to 3.3 mm with a lesion length of 10 to 18 mm. The ejection fraction is 45% or more. There are no signs of calcification and thrombosis in the affected area.

Patients underwent coronary stenting 6-8 months before admission. In this case, a stent with a diameter of 3.0-4 mm is implanted with a length of 10 to 20 mm, with the stent completely covering the lesion area. Residual stenosis in the area of stent implantation is 5% or less in the absence of edge dissection and deceleration of blood flow in the target artery after stent implantation.

6-8 months after coronary stenting, patients seek advice with complaints of pain in the heart, shortness of breath. An angiographic study determines the narrowing of the lumen in the stent by 50% or more (1.7 mm or more of the reference diameter), which gives reason to judge the development of restenosis.

Patients are selected for the subsequent prediction of the development of restenosis: men aged 40 to 65 years with stable angina pectoris I-III functional class; in the absence of a history of diabetes mellitus and other pathologies of the endocrine system; as well as in the absence of a history of intolerance to sulfa drugs and caffeine.

Nitrogen-containing compounds — sulfadimesin (at a dose of 250-500 mg), caffeine (at a dose of 150-300 mg), etc. were used as a test drug. 6 hours after a single oral administration of the drug, urine was collected and the ratio was determined using high-performance liquid chromatography N-acetyl derivative to a non-metabolized drug. With rapid acetylation, the acetylation coefficient is more than 73%. At the same time, the course of coronary heart disease is predicted as more severe with a high probability of developing instant restenosis after the coronary agency procedure.

Subsequent coronary stenting revealed that long-term positive results of the operation were observed only in patients with slow acetylation - 73% or less.

The method is further explained by examples of its implementation.

Example 1

Patient D. was admitted with a diagnosis of coronary heart disease. Unstable angina, PIX (myocardial infarction of the anterior wall of the left ventricle). Condition after stenting of the middle third of the anterior interventricular branch.

From the history of the disease, it is known that without previous angina pectoris suffered a Q-forming myocardial infarction of anterior-widespread localization; was in hospital treatment. The ejection fraction is 45%. Akinesis of the anterolateral and apical segments of the left ventricle. Stenosis of the anterior interventricular branch in the middle third by 50%. OV, PKA not changed, performed TLAP avg. / 3 PMZHV. The condition remained stable for about 1 month; in the future - the return of angina pectoris, administration of nitroglycerin. Transferred repeated myocardial infarction of anterior-widespread localization; was in hospital treatment. After 8 months. a follow-up examination revealed restenosis after TLAA by 75%, performed TLAA and stenting of the anterior interventricular branch with a positive angiographic result. After discharge, pain of an anginal nature was not disturbed. Currently on therapy: Crestor 10 mg / day, Nebilet 5 mg / day, Plavix 75 mg / day, Prestarium 2 mg / day, Thrombo ACC 100 mg / day. Six months later, wave-like pains appeared in the left half of the chest cavity of a aching nature, with a positive effect from nitrates.

Status at admission: moderate. Position: not forced. Skin, mucous membranes: normal color and humidity. Subcutaneous tissue: well defined. Lymph nodes: not enlarged. Osteoarticular system: without pathology. Thyroid: not enlarged. Swelling: no.

Respiratory organs: chest: regular shape. BH: 16. Percussion sound: pulmonary. Auscultatory: vesicular breathing, carried out in all departments. No wheezing.

Circulatory system. Pathological pulsation: no. The boundaries of the relative dullness of the heart are within normal limits. Auscultatory: tones are muffled, rhythmic, no noise. Heart rate: 59 rpm. HELL: 120/80. Noises in the projection of the femoral and carotid arteries are not heard. Ripple in the peripheral arteries is satisfactory.

Digestive organs. Appetite, swallowing: not disturbed. Tongue: wet, pink. Belly: soft, b / w. Liver: not palpable. Spleen: not palpable.

Consciousness: clear. Memory: saved. Hearing: saved. Vision: saved, astigmatism. Focal symptoms: not detected. Meningic symptoms: no.

ECG (admission): ECG: sinus rhythm, correct, heart rate: 66 beats. in minutes Cicatricial stage of the Q-forming anterior-septal region of the left ventricle of myocardial infarction.

Performed coronary angiography.

Ventriculography: BWW 135 ml, KSO 62 ml. The ejection fraction is 45%. Mitral regurgitation is absent. Segmental contractility (right oblique projection): ankinesis of the anterolateral, hypokinesis of the apical segments. Selective coronarography: the type of coronary circulation is left. The trunk of the left coronary artery is usually developed, not changed. Anterior ventricular branch: restenosis after stenting 75%. The lesion area is 4 mm, the extent of the lesion is 18 mm. The enveloping branch, the right coronary artery is not changed.

An in-stent stenosis of the middle segment of the anterior interventricular branch was performed using a balloon with a diameter of 4 mm and a length of 20 mm with a satisfactory angiographic effect. The inner surface of the stent is coated with paclitaxel - 1 μg / mm ² , which has a biphasic release kinetics in accordance with the healing phases of the vessel with a “burst” at the beginning and slow release for 31 days. After this period, the release of the drug does not occur. Paclitaxel in the doses used does not show a cytotoxic effect, but is a cytostatic, slowing down the division of smooth muscle cells and the secretion of extracellular matrix, without inhibiting the division of endothelial cells.

The postoperative period was uneventful. During the hospital stay, the patient's condition remained stable: anginal pain did not recur, hemodynamic parameters remained stable: NPV = 16 per min, heart rate = 69 beats / min, blood pressure 120/80 mm RT. Art.

Clinical blood and urine tests, biochemical analysis of blood without features.

A study of the “fast” acetylation phenotype with caffeine in a dose of 150 mg. 6 hours after a single oral administration of the drug in urine, the ratio of the N-acetyl derivative to the non-metabolized drug (caffeine) was determined by liquid chromatography. The acetylation coefficient is 74%.

When conducting Holter monitoring of rhythm and conduction disturbances was not detected. The ST segment is stable.

With echocardiography: the cavity of the heart is not expanded. Left ventricle contractility: reduced, the nature of the movement - akinesia, localization - the apex, anterior wall, interventricular septum, level - the middle and apical third, ejection fraction of 45%; end-diastolic size: in the parasternal position 5.0 cm; finite systolic size: in the parasternal position 4.0 cm; end-diastolic volume 116 cm ³ ; finite systolic volume 71 cm ³ ; the thickness of the interventricular septum in diastole is 6 mm; the thickness of the back wall in diastole is 8 mm. The aorta is not expanded - 3.0 cm. Mitral valve: the movement of the valves is multidirectional, with D-echo regurgitation in the left atrium of the first degree.

The patient received medication with nitrates, ACE inhibitors, β-blockers, antiplatelet agents (Trombo Ass 100 mg / day, Plavix 75 mg / day), statins.

Subsequently, the patient was discharged from the hospital with recommendations for further treatment, compliance with the diet, labor and follow-up examination after 6 months.

Example 2

Patient S., 58 years old, was admitted with a diagnosis of coronary heart disease.

Condition after direct stenting of the middle third of the anterior interventricular branch. Hypertension 2 tbsp. Heart rhythm disturbance: supraventricular ventricular extrasystole.

From the medical history of the disease, it is known that the patient suffers from hypertension from 55 years. The maximum blood pressure is 180/100, adapted to 130/80 mmHg. Art. IHD since 2003, when there were pains behind the sternum during exercise. In 2004, an intense anginal attack stopped on his own. Subsequently, an increase in angina attacks, a decrease in exercise tolerance was noted.

With coronary angiography - stenosis of the middle third of the anterior interventricular branch by 50%. Slowing antegrade filling of coronary arteries. The reference diameter of the artery in the lesion area is 3.3 mm with a lesion length of 10 mm.

Stenting of the middle third of the anterior interventricular branch was performed. A stent with a diameter of 3.5 mm and a length of 12 mm is implanted.

Over the next 3 months, the return of angina pectoris (with high physical exertion). Accepts: sotaleks 40 mg × 2 times a day, enap 5 mg × 2 times a day, thromboass, furosemide 40 mg per day. Zocor 10 mg × at night. During the examination, the load test is not informative. He was hospitalized for control CAG.

Objective status: admission status: relatively satisfactory Position: not forced. Constitutional features: no features. Skin, mucous membranes: normal color and humidity. Subcutaneous tissue: well defined. Lymph nodes: not enlarged. Bone-articular system: osteochondrosis of the spine. Thyroid: not enlarged. Swelling: no.

Chest: regular shape. BH: 16. Percussion sound: pulmonary. Auscultatory: vesicular breathing, performed in all departments. No wheezing.

Borders of relative dullness of the heart: extended to the left 1 cm outward from the left midclavicular line. Auscultatory: tones are muffled, rhythmic, systolic murmur at the apex. Heart rate: 57 rpm. HELL: 130/80 mmHg Art. No noise is heard in the projection of the femoral and carotid arteries. Ripple in the peripheral arteries is satisfactory. Tongue: wet, pink. Belly: soft. Liver: not palpable. Spleen: not palpable. Urination: free. S. Pasternatsky: negative on both sides. Consciousness: clear. Memory: saved. Hearing: saved. Vision: reduced, saved. Focal symptoms: not detected. There is no meningeal symptomatology.

On ECHO-KG: SLP - 21.7 square meters. cm expanded, pancreas not expanded - 2.4 cm. Left ventricle, contractility: satisfactory, ejection fraction 68%, end-diastolic size: in the parasternal position 5.8 cm; finite systolic size: in the parasternal position 4.1 cm; the thickness of the interventricular septum in diastole is 9 mm; the thickness of the back wall in diastole is 9 mm. The aorta is compacted with signs of calcification, not expanded - 3.1 cm. Aortic valve - valves are sealed, opening amplitude - 1.7 cm. Mitral valve - valve movement is multidirectional, valves are sealed.

Bicycle ergometry result: initial heart rate (HR) 63 beats. in minutes Bicycle ergometry result: initial systolic pressure 130 mm RT. st .; initial diastolic pressure of 80 mm RT. st .; achieved level and time of termination of the load: power 125 W - 2 min, 42 s; maximum pressure: systolic - 200 mm RT. st .; maximum pressure: diastolic - 90 mm RT. st .; criterion for termination of the load - due to patient fatigue, proper submaximal rhythm - 140 beats. in minutes (age 50-59 years). Bicycle ergometry result: achieved rhythm - 125 beats. in min .; ECG changes are not available. Evaluation of the sample is not informative due to patient fatigue, average load tolerance (100-125 W).

Electrocardiography: sinus rhythm, heart rate 65 beats. in minutes; rhythm disturbance - extrasystole: by source - ventricular, Laun group - 3-4 (multimorphic extrasystole, sometimes paired extrasystole) EOS is rejected to the left, no changes in the ST-T segment were detected.

Clinical blood and urine tests, biochemical analysis of blood without features.

The study of the phenotype of acetylation with caffeine in a dose of 300 mg. 6 hours after a single oral administration of the drug in urine, the ratio of the N-acetyl derivative to the non-metabolized drug (caffeine) was determined by liquid chromatography. The acetylation coefficient is 73%. The acetylation phenotype is “slow”.

Diagnostic angiography. Ventriculography: end-diastolic volume of 127 ml, end-systolic volume of 42 ml. The ejection fraction is 68%. Mitral regurgitation is absent. Segmental contractility (right oblique projection): satisfactory. Selective coronarography. The type of coronary circulation is right. Left coronary artery: the trunk of the LCA is usually developed, not changed. Anterior ventricular branch: in the middle third, the state after stenting without restenosis, proximal to the stent is stenosed by 30-40%. Envelope branch, right coronary artery: irregularities in the contours.

The postoperative period was uneventful. During the hospital stay, the patient's condition remained stable: anginal pain did not recur, hemodynamic parameters remained stable: NPV = 16 per minute, heart rate = 69 beats / min, blood pressure - 120/80 mm RT. Art.

The patient received medication with nitrates, ACE inhibitors, antiarrhythmic drugs, β-blockers, antiplatelet agents, and statins. Subsequently, the patient was discharged from the hospital with recommendations for further treatment, compliance with diet and labor.

Example 3

Patient M., 53 years old, was admitted with a diagnosis of coronary heart disease: a condition after direct stenting of the middle third of the right coronary artery. Hypertension 2 tbsp.

From the anamnesis of the disease, it is known that the patient suffers from hypertension from 50 years. The maximum blood pressure is 170/100, adapted to 120/80 mmHg. Art. IHD since 2002, when there were pains behind the sternum during exercise. He was treated in various hospitals. Increased seizures within 3 months.

Coronary angiography - stenosis of the middle third of the right coronary artery by 75%. The reference diameter of the artery in the lesion area is 3.2 mm with a lesion length of 15 mm.

Stenting of the middle third of the right coronary artery was performed. A stent with a diameter of 3.5 mm and a length of 18 mm is implanted. The inner surface of the stent is coated with paclitaxel. The high lipophilicity of paclitaxel provides rapid penetration into the vessel wall and slows the proliferation of smooth muscle cells. Optimization of delivery in the form of a low profile of the cylinder reduces the friction force and allows the device in vessels of 2 mm Synthetic glycocalyx surface treatment of the stent creates a natural shield against blood clots.

After discharge, she feels well, anginal pains do not bother. Physical exercise tolerates well. Accepts: concor 5 mg × 1 time per day, enap 5 mg × 2 times per day, thromboass 100 mg × 1 time per day, plavix 75 mg × 1 time per day. Zocor 10 mg × at night. During the examination, the load test is negative. He was hospitalized for control CAG.

Objective status: Status upon receipt: relatively satisfactory. Position: not forced. Constitutional features: no features. Skin, mucous membranes: normal color and humidity. Subcutaneous tissue: well defined. Lymph nodes: not enlarged. Bone-articular system: osteochondrosis of the spine. Thyroid: not enlarged. Swelling: no.

Chest: regular shape. BH: 16. Percussion sound: pulmonary. Auscultatory: vesicular breathing, performed in all departments. No wheezing.

Borders of relative dullness of the heart: extended to the left 1 cm outward from the left midclavicular line. Auscultatory: tones are muffled, rhythmic, systolic murmur at the apex. Heart rate: 57 rpm. HELL: 130/80 mmHg Art. No noise is heard in the projection of the femoral and carotid arteries. Ripple in the peripheral arteries is satisfactory. Tongue: wet, pink. Belly: soft. Liver: not palpable. Spleen: not palpable. Urination: free. S. Pasternatsky: negative on both sides. Consciousness: clear. Memory: saved. Hearing: saved. Vision: reduced, saved. Focal symptoms: not detected. There is no meningeal symptomatology.

On ECHO-KG: SLP -21.7 sq. cm expanded, pancreas not expanded - 2.5 cm. Left ventricle, contractility: satisfactory, ejection fraction of 65%, end-diastolic size: in the parasternal position 5.7 cm; finite systolic size: in the parasternal position 4.0 cm; the thickness of the interventricular septum in diastole is 8 mm; the thickness of the back wall in diastole is 9 mm. The aorta is compacted with signs of calcification, not expanded - 3.3 cm. Aortic valve - valves are sealed, opening amplitude - 1.7 cm. Mitral valve - valve movement is multidirectional, valves are sealed.

Bicycle ergometry result: initial heart rate (HR) 63 beats. in minutes Bicycle ergometry result: initial systolic pressure 130 mm RT. st .; initial diastolic pressure of 80 mm RT. st .; achieved level and time of termination of the load: power 125 W - 3 min, 42 s; maximum pressure: systolic - 180 mm RT. st .; maximum pressure: diastolic - 90 mm RT. st .; the criterion for the termination of the load is the achievement of submaximal heart rate, proper submaximal rhythm is 140 beats. per minute (age 50-59 years), the achieved rhythm is 141 beats. in minutes; ECG changes are not available. Sample rating is negative, average load tolerance (100-125 W).

Electrocardiography: sinus rhythm, correct. Heart rate 65 beats. in minutes EOS is rejected to the left, no changes in the ST-T segment were detected.

Clinical blood and urine tests, biochemical analysis of blood without features.

The study of the phenotype of acetylation with caffeine in a dose of 300 mg. 6 hours after a single oral administration of the drug in urine, the ratio of the N-acetyl derivative to the non-metabolized drug (caffeine) was determined by liquid chromatography. The acetylation coefficient is 73%. The acetylation phenotype is “slow”.

Diagnostic angiography. Ventriculography: end-diastolic volume of 125 ml, end-systolic volume of 44 ml. The ejection fraction is 66%. Mitral regurgitation is absent. Segmental contractility (right oblique projection): satisfactory. Selective coronarography. The type of coronary circulation is right. Left coronary artery: the trunk of the LCA is usually developed, not changed. The anterior interventricular branch, the envelope of the branch without hemodynamically significant changes. The right coronary artery in the middle third, the state after stenting without restenosis.

The postoperative period was uneventful. During the hospital stay, the patient's condition remained stable: anginal pain did not recur, hemodynamic parameters remained stable: NPV = 16 per minute, heart rate = 69 beats / min, blood pressure - 120/80 mm RT. Art.

The patient received medication with ACE inhibitors, β-blockers, antiplatelet agents, and statins.

Subsequently, the patient was discharged from the hospital with recommendations for further treatment, compliance with diet and labor.

Subsequent coronary stenting revealed that long-term positive results of the operation were observed only in patients with slow acetylation - 73% or less.

According to the method for predicting the degree of risk of developing restenosis in the coronary stent, 98 patients were diagnosed. Achieved the achievement of the objectives of the invention in 96 patients.

Information sources

1. Hirshfeld J.W. Jr., Schwartz J.S., Jugo R., MacDonald R.G., Goldberg S., Savage M.P., et al. Restenosis after coronary angioplasty: a multivariate statistical model to relate lesion and procedure variables to restenosis. The M-HEART Investigators. J Am Coll Cardiol 1991; 18: 647-56. 31-133.

2. Osiev A.G., Grazhdankin I.O. Percutaneous coronary interventions in patients with diabetes mellitus: The obvious cannot be ignored. Found on the Internet: Google http://www.infarktu.net/upload/files/teksti.doc.

Claims (1)

A method for predicting the risk of developing restenosis in the coronary stent, including determining the metabolic rate of a nitrogen-containing drug by administering a test drug, characterized in that caffeine is used as a test drug in a dose of 150-300 mg orally once, then after 6 hours it is determined in urine the ratio of the N-acetyl derivative to the non-metabolized drug, and with a ratio of 73% or lower, a favorable stenting outcome is predicted.