RU2748010C1 - Method for predicting development of restenosis of coronary artery after stenting with bare metal or drug-eluting stent in patients with ischemic heart disease - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, in particular to cardiology, X-ray endovascular surgery, and discloses a method for predicting the likelihood of restenosis after coronary artery stenting. The method is characterized in that the patient's blood is taken and the values of the neutrophil-lymphocyte ratio (NLS), the width of distribution of erythrocytes by volume (RDW), the mean platelet volume (MPV) are recorded in physical quantities, then the Gensini index is calculated during coronary angiography, after which the probability of developing restenosis (hi (t)) is calculated according to the formula developed by the inventors.

EFFECT: invention improves accuracy of predicting the occurrence of restenosis after stenting with a bare metal stent and a drug-eluting stent in patients with coronary heart disease by taking into account clinical (gender, diabetes mellitus), laboratory (RDW, MPV, NLS) and angiographic parameters (Gensini index) and can be used to predict the occurrence of restenosis of bare metal and coated stents in coronary arteries during percutaneous coronary intervention in patients with ischemic heart disease.

1 cl, 1 dwg, 1 tbl

Description

The invention relates to medicine, in particular to cardiology, X-ray endovascular surgery and can be used to predict the occurrence of restenosis of bare metal and coated stents in coronary arteries during percutaneous coronary intervention in patients with coronary heart disease.

Stenting of the coronary artery in acute coronary syndrome allows you to preserve the myocardium, avoid complications of the acute period, and the progression of chronic heart failure. With chronic ischemic heart disease, it can significantly improve the patient's quality of life. However, this method has disadvantages: restenosis within the stent, stent thrombosis. [Buccheri D. et al. Understanding and managing in-stent restenosis: a review of clinical data, from pathogenesis to treatment // J. Thorac. Dis. 2016. Vol. 8, no.10. P. E1150-E11621]. Coronary stent, which is essentially an intravascular prosthesis, solved the problem of elastic collapse of the vessel walls, however, a new problem was identified - restenosis within the stent due to the proliferation of neointima, consisting mainly of smooth muscle cells and extracellular matrix [Christen T. et al. Mechanisms of Neointima Formation and Remodeling in the Porcine Coronary Artery // Circulation. 2001. Vol. 103, no. 6. P. 882-888.2]. The occurrence of hemodynamically significant restenosis of the coronary artery after stenting leads to stent failure, which in turn is the cause of the recurrence of myocardial ischemia in the form of stable angina pectoris of various functional classes or acute coronary syndrome in the form of unstable angina pectoris or myocardial infarction type 4C [Chen M.S. et al. Bare metal stent restenosis is not a benign clinical entity // Am. Heart J. 2006. Vol. 151, no. 6. P. 1260-1264.3]. All this dictates the need for repeated coronary angiography and elimination of restenosis by either re-stenting the affected vessel, or using the method of balloon angioplasty with a conventional balloon or a drug-eluting balloon [Alfonso F. et al. Current Treatment of In-Stent Restenosis // J. Am. Coll. Cardiol. 2014. Vol. 63, no.24. P. 2659-26734]. Recurrent coronary events pose a threat to the patient's health, cause a decrease in the quality of life and are associated with high economic costs in health care [Nayak A.K. et al. Myocardial Infarction as a Presentation of Clinical In-Stent Restenosis // Circ. J. 2006. Vol. 70, no.8. P. 1026-10295].

Despite numerous domestic and foreign studies, the authors' opinions on the risk factors for restenosis after stenting differ, therefore, the search for predictors of coronary artery restenosis after stenting is relevant at the moment [Byrne RA, Joner M., Kastrati A. Stent thrombosis and restenosis: what have we learned and where are we going? The Andreas Griintzig Lecture ESC 2014 // Eur. Heart J. 2015. Vol. 36, no. 47. p. 3320-3331].

It is known to use heart rate to predict stent restenosis during percutaneous coronary intervention in patients with ischemic heart disease in the late postoperative period (Patent RU No. 2662413 C1, IPC А61В 5/00 - 25.07.2018, bull. No. 21), the essence of which is as follows : the patient after percutaneous coronary intervention is measured by the heart rate. The obtained value is substituted into the declared mathematical model of the risk of developing restenosis in the coronary stent in the late postoperative period. EFFECT: method facilitates predicting restenosis of stents in coronary arteries during percutaneous coronary intervention in patients with ischemic heart disease by assessing the most significant indicator. However, the disadvantage of this technique is that it does not take into account the laboratory and other clinical parameters of the patient, the diameter of the stentable vessel and the length of the implanted stent.

Also known is a method for the diagnosis of restenosis of coronary arteries after endovascular myocardial revascularization (Patent RU No. 2308884, IPC А61В 5/0452 - 10/27/2007, bull. No. 30), characterized by the fact that the heart rate variability is assessed while taking α1β1β2-adrenergic blocker during 2 weeks. In this case, heart rate variability is assessed by recording an ECG for 6 minutes under the conditions of a standard 6-minute walk test against the background of the abolition of coronary active drugs. The α1β1β2-adrenergic blocker acridilol is prescribed at an average dose of 25 mg / day. Then, an ECG is re-recorded with an assessment of the heart rate variability after 2 weeks of monotherapy course under conditions of stress testing. Restenosis of the coronary artery is diagnosed with an increase in the indicators of the general level of neurohumoral regulation SDNN by 47.7% and SDANN by 59.2%, the degree of predominance of the parasympathetic link of regulation over the sympathetic pNN50 by 93.3% and the relative level of activity of the parasympathetic link of HF regulation by 90.5 %. The disadvantage of this method is the lack of analysis of concomitant diseases that can affect the development of restenosis, the lack of assessment of laboratory risk factors.

A known method for predicting the development of restenosis after stenting coronary arteries with stents without drug coverage (Patent RU No. 2395091, IPC G01N 33/53 - 20.07.2010, bull. No. 20). Why determine the genotypes of polymorphisms Glu298Asp of the endothelial nitric oxide synthase gene (eNOS) and Prol98Leu of the glutathione peroxidase-1 (GPx-1) gene. When only the Glu298 and Pro 198 alleles are detected in the patient, the Glu298Asp polymorphisms of the eNOS gene and the Prol98Leu polymorphisms of the GPx-1 gene predict a low risk of restenosis. If either the 298Asp allele of the Glu298Asp polymorphism of the eNOS gene or the 198Leu allele of the Prol98Leu polymorphism of the GPx-1 gene is detected, the average risk of restenosis is predicted. When the 298Asp allele of the Glu298Asp polymorphism of the eNOS gene and the 198Leu allele of the Prol98Leu polymorphism of the GPx-1 gene are identified, a high risk of restenosis is predicted. The disadvantage of this method is that it does not allow to quantify the likelihood of developing restenosis.

The closest in technical essence is a method for predicting restenosis in patients undergoing stenting of the right coronary artery, anterior interventricular branch, the circumflex branch and branches of the obtuse edge of the left coronary artery (Patent RU No. 2532340 C2, IPC G01N 33/48, G01N 33/68 - 10.11 .2014, bull. No. 31). The essence of the method lies in the fact that during stenting, blood is taken from the patient's ulnar vein and the prothrombin index, the content of very low density lipoproteins, high density lipoproteins, the atherogenic index are assessed, the size of the stenosis is determined, and then the prognostic coefficient is determined using the formula. However, the use of the prothrombin index in this method is not entirely correct, since this indicator can change when taking antiplatelet agents and during stenting, this group of drugs is prescribed in a loading dose that exceeds the daily average by 8 times. In addition, based on modern clinical recommendations, the content of low density lipoproteins is prognostically important, and the atherogenic index is of secondary importance, and this method does not take into account such known risk factors for restenosis as diabetes mellitus, smoking, and indicators of inflammatory status.

This invention is taken as a prototype.

The objective of the present invention is to create a prognostic model of the occurrence of restenosis of the coronary artery after stenting.

The utility of the claimed method lies in predicting the occurrence of restenosis of the coronary artery after stenting with a bare metal or drug-eluting stent.

The technical result of the claimed invention is to improve the accuracy of predicting the occurrence of restenosis after stenting with a bare metal stent and a drug-eluting stent in patients with coronary heart disease by taking into account clinical (gender, diabetes mellitus), laboratory (erythrocyte volume distribution width (RDW), average platelet volume (MPV), neutrophil-lymphocyte ratio (NLS)) and angiographic parameters (Gensini index).

Until now, this set of parameters has not been used to predict the occurrence of restenosis of the coronary arteries.

The technical result of the claimed invention is achieved due to the fact that the risk of restenosis after stenting is calculated by substituting the corresponding variables in the formula of proportional risks depending on the patient's gender, the presence of diabetes mellitus, parameters of the general blood test (RDW, MPV, neutrophil-lymphocyte ratio), index Gensini, calculated according to the protocol of coronary angiography.

The difference is that a complex of clinical (female gender, diabetes mellitus), laboratory (RDW, MPV, NLS) and angiographic parameters (Gensini index) is used to predict the occurrence of coronary artery restenosis after stenting, the likelihood of coronary artery restenosis after stenting is estimated by the formula :

h _i (t) = h0 (t) x exp (β1X1 + β2X2 + β3X3 + β4X4 + β5X5 + β6X6),

where X1-X6 are independent variables that take values from 0 to 1 in the presence or absence of a feature, and β1-β10 are constants that take the following values:

β1 - 0.918, β2 - 0.618, β3 - 0.40, β4 - 0.674, β5 - 0.770, β6 - 1.247.

The essence of the invention is illustrated by drawings, which show:

FIG. 1 - Analysis of the accuracy of the predictive scale using ROC curves (ROC analysis).

To assess the accuracy of the prognostic scale of the proposed method was used ROC - analysis (Fig. 1), in which the value of the area under which (C-statistics) reflects the diagnostic strength of the model (the ideal model approaches 1.0). Thus, the C-statistic of the proposed method was 0.73 (0.68-0.79), p <0.001.

The advantage provided by the above set of features is the prediction of the risk of coronary artery restenosis after stenting in patients with acute and chronic forms of coronary artery disease already in the admission-diagnostic department before the procedure of percutaneous coronary intervention; the possibility of intervening in the stenting process in order to correct the identified predictors.

The method is carried out as follows.

To predict the risk of coronary artery restenosis after stenting with a bare metal or drug-eluting stent prior to percutaneous coronary intervention, the following indicators are studied:

- Complete blood count (hemoglobin, the absolute number of erythrocytes in 1 ml of blood, the absolute number of leukocytes in 1 ml of blood, the absolute number of platelets in 1 ml of blood; leukocyte formula with the calculation of the absolute number of neutrophils, lymphocytes, monocytes, eosinophils, the width of distribution of erythrocytes by volume (RDW), mean platelet volume (MPV), the neutrophil-lymphocyte and lymphocyte-platelet ratio was calculated by calculating the ratio of the absolute number of corresponding cells in 1 ml of blood);

- Biochemical blood test (glucose, total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), triglycerides, total bilirubin, alanine aminotransferase, aspartate aminotransferase, creatinine);

- Coagulogram (APTT, prothrombin time, prothrombin index, Quick fibrinogen);

- Presence / absence of type 2 diabetes mellitus, hyperlipidemia, arterial hypertension.

Coronary angiography and stenting of the coronary artery are performed with a detailed description of the lesions of the basins of the left and right coronary arteries, the type of stent being implanted, the diameter and length of the stent, reflected in the study protocol. According to the coronary angiography protocol, the Genisni scale was used to calculate the index of the severity of coronary lesions.

For statistical analysis, a step-by-step Cox regression analysis algorithm was used (SPSS 23 software from SPSS Inc. (USA)), which allows determining the most diagnostically sensitive and specific combination from the proposed data. Of the many listed indicators, the following were identified as predictors of restenosis in the stent: female sex, diabetes mellitus, RDW> 11.9%, MPV> 8.25 fl, neutrophil-lymphocyte ratio> 1.72, Gensini index> 15.3 points ( Table 1):

The method is illustrated by specific clinical examples. Example 1. Patient F., 49 years old, was admitted to the admission-diagnostic department of the clinic with a diagnosis of ischemic heart disease. Unstable angina. From the anamnesis it is known that the patient suffers from type 2 diabetes mellitus and arterial hypertension. I do not smoke. Laboratory data: RDW - 16.29%, MPV - 9.3 fl, NLS - 2.25. The Gensini Index is 65 points. Stenting of the anterior interventricular branch was performed with 1 Driver 2.75x24 mm stent. ECG: sinus rhythm, the electrical axis of the heart is deflected to the left, heart rate 72 beats / min, c.ST on the isoline. According to the prognostic scale, the risk of restenosis in this patient is calculated: 51.1%. 4 months after percutaneous coronary intervention, the patient is admitted to the clinic with the return of symptoms of myocardial ischemia, diagnosed with ischemic heart disease. Unstable angina. A repeat coronary angiography is performed - 60% restenosis was revealed inside the stent of the anterior interventricular branch.

Example 2. Patient V., 56 years old, was admitted to the admission-diagnostic department of the clinic with a diagnosis of ischemic heart disease. Myocardial infarction without CST elevation of the lower wall of the left ventricle. From the anamnesis it is known that the patient does not suffer from type 2 diabetes mellitus and arterial hypertension. I do not smoke. Laboratory data: RDW - 10.84%, MPV - 7.2 fl, NLS - 2.36. The Gensini index is 13 points. Stenting of the right coronary artery with 1 bare metal stent was performed. ECG: sinus rhythm, electrical axis of the heart - normogram, heart rate 90 beats / min, depression c.ST up to 2 mm in leads II, III, AvF. According to the prognostic scale, the risk of restenosis in a given patient is calculated: 1.1%). 3 months after percutaneous coronary intervention, the patient is admitted to the clinic with the return of symptoms of myocardial ischemia, and a diagnosis of ischemic heart disease is made. Unstable angina. Repeated CAG was performed - restenosis inside the stent of the right coronary artery was not detected, stenting of the anterior interventricular branch was performed.

The proposed method makes it possible to more effectively control the course of restenosis of the coronary artery inside the stent, caused by neointimal hyperplasia and neontimal atherosclerosis.

Claims (13)

A method for predicting the likelihood of developing restenosis after stenting coronary arteries, which consists in calculating the likelihood of developing restenosis after stenting with both bare metal and drug-eluting stents, characterized in that it additionally takes into account the parameters of the general blood test, which are the distribution width of erythrocytes by volume (RDW), mean platelet volume (MPV), neutrophil-lymphocyte ratio (NLS), clinical parameters representing the sex of the patient, the presence or absence of diabetes mellitus, and the angiographic parameter representing the Gensini index, At the same time, before stenting, the patient's blood is taken and the values of NLS, RDW, MPV are recorded in physical quantities, then, during coronary angiography, the Gensini index is calculated, after which the probability of restenosis development (hi (t)), expressed as a percentage, is calculated using the formula: hi (t) = h0 (t) x exp (β1X1 + β2X2 + β3X3 + β4X4 + β5X5 + β6X6), where X1-X6 are independent variables that take values from 0 to 1 in the presence or absence of a sign: X1 - gender, 0 - male, 1 - female; X2 - diabetes mellitus, 0 - absence; 1 - availability; X3 - RDW, 0 - RDW <11.9% or RDW = 11.9%; 1 - RDW> 11.9%; X4 - MPV, 0 - MPV <8.25 fl or MPV = 8.25 fl; 1 - MPV> 8.25 fl; X5 - NLS, 0 - NLS <1.72 or NLS = 1.72; 1 - NLS> 1.72; X6 - Gensini index, 0 - Gensini index <15.3 points or Gensini index = 15.3 points; 1 - Gensini index> 15.3 points; h0 (t) is the basic risk, which takes values from 0.001 with 1 month of observation, 0.014 with 6 months of observation, 0.026 with observation for 1 year, 0.055 - 2 years, 0.085 - 3 years, and β1-β6 are constants that take the following values: β1 - 0.918, β2 - 0.618, β3 - 0.40, β4 - 0.674, β5 - 0.770, β6 - 1.247.

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