RU2426124C1 - Method of prediction of prevalence of stenotic transplant coronary bed lesion in recipients following cardiac transplantation - Google Patents

Abstract

FIELD: medicine. ^ SUBSTANCE: blood plasma is analysed for a cardiolipin antibody level. If at least two studies has shown an upper limit of the reference blood plasma cardiolipin antibody limits exceeded by 10-20%, the one-vascular stenotic lesion is predicted. The multivascular stenotic bed lesion is proven by at least two studies showing an upper limit of the reference blood plasma cardiolipin antibody limits exceeded by more than 21%. ^ EFFECT: use of the method allows predicting a severity of bed lesion in a patient, sizing the possibilities of subsequent treatment. ^ 4 dwg, 3 ex

Description

The invention relates to medicine, namely to transplantology, and can be used to predict the prevalence of stenotic lesions of the coronary bed after heart transplantation.

Transplanted heart coronary artery disease (BACPS) is the most common cause limiting the life expectancy of patients with a transplanted heart. The identification and assessment of risk factors for the development of this severe postoperative complication allows us to identify groups of patients requiring more careful monitoring and treatment, to improve the quality and life expectancy of patients with a transplanted heart.

There is a method for predicting the development of BCAPS in cardiac recipients by assessing the levels of antibodies to cardiolipin in cardiac recipients, suggesting that when reference values of ACL are exceeded, stenotic lesion of the coronary bed develops (Shumakov V.I., Shevchenko O.P., Kazakov E.N. ., Chestukhin V.V., Kormer A.Ya., Halilulin T.A., Orlova O.V., Shumakov D.V. Prognostic value of antibodies to cardiolipin in case of transplanted heart vasculopathy. Cardiology and cardiovascular surgery, 2008, No. 3, pp. 59-64). Nevertheless, this technique does not allow to predict the degree of subsequent lesion of the patient’s coronary bed, to evaluate the possibilities of further treatment. No methods have been found in the literature to predict the development of a single-vessel or multi-vessel stenotic lesion of the coronary arteries of a transplanted heart.

The task is to develop a method for predicting the prevalence of coronary lesions after heart transplantation at the stage of preoperative examination, as well as from 1 to 24 months after surgery.

The technical result consists in the possibility of predicting the prevalence of coronary lesion by detecting a single-vascular stenotic lesion of the coronary arteries after heart transplantation when exceeding the upper boundary of the reference values of the level of antibodies to blood plasma cardiolipin in two or more studies by 10-20%, and when exceeding the upper boundary of the reference values of the level of antibodies to blood plasma cardiolipin in two or more studies by 21% or more - multivascular, common stenotic Skogen coronary arteries.

The invention consists in the following.

The level of antibodies to cardiolipin in cardiac recipients is assessed at the stage of preoperative examination and / or within 1 to 24 months after surgery. When exceeding the upper boundary of the reference values of the level of antibodies to blood plasma cardiolipin in two or more studies by 10-20%, the development of an isolated, single-vessel stenotic lesion of the coronary arteries after heart transplantation is predicted. If the upper limit is exceeded in two or more studies by more than 21%, the development of multivascular stenotic lesion of coronary arteries of a transplanted heart is predicted.

The method is as follows.

To achieve a technical result at the stage of preoperative examination and / or within 1 to 24 months after heart transplantation using enzyme-linked immunosorbent assay in patients, the level of antibodies to cardiolipin is assessed using the AKL kit Diagnostic Systems Laboratory (Russia) or Orgentec diagnostika GMBH "(Germany). Patients with signs of inflammation or infection confirmed by clinical and laboratory methods (SRV above 5 mg / L, elevated ESR, changes in the blood formula, subfebrile or febrile body temperature, etc.) are excluded from the study on the assessment of AKL levels. The study does not include patients with morphological signs of acute cellular and humoral rejection of a transplanted heart (confirmed by immunohistochemical and morphological studies of myocardial biopsy samples).

This method was developed by the Federal State Institution Federal Scientific Center TiIO named after ac. V.I.Shumakova. Before surgery and up to 10 years after TS, 25 patients were examined. In order to assess the levels of antibodies to cardiolipin, more than 130 diagnostic tests were performed. The diagnosis of BCAPS was established according to a coronary angiographic study conducted annually. In 4 patients, a single-vessel lesion of the coronary arteries of the transplanted heart after heart transplantation was confirmed, in 6 - a multi-vessel. In the remaining patients of the control group with the level of antibodies to cardiolipin not exceeding the upper limit of the reference values, coronary lesions were not detected during the entire observation period.

In patients with multivascular coronary lesions, the level of antibodies to cardiolipin significantly exceeded the parameters of patients with isolated coronary artery lesions of 23.0 ± 6.59 IU / ml and 37.96 ± 24.41 IU / ml, respectively, p = 0.005.

Figure 1, position 1, presents the ACL data of patients with isolated single-vessel coronary lesion (4 patients, 26 studies), Figure 1, position 2, - patients with multi-vessel coronary lesion (6 patients, 24 studies).

The presented trend is manifested both in the period before surgery and in the period up to 2 years after the vehicle.

When the level of antibodies to cardiolipin exceeds the upper limit of reference values by 10-20%, the development of a single-vessel lesion of the coronary arteries is predicted. Patients of this group, with isolated lesions of the coronary arteries, had discrete stenoses in the permanent pancreas or PKA, which were identified during annual planned coronary angiographic studies.

Example 1. As a clinical example, the patient is considered J., 17 years old. Heart transplantation was performed on November 17, 2000. The patient had elevated levels of AKL before the TS (25 and 28 IU / ml). In the postoperative period, AKL levels also remained elevated: 26, 23, 24, 25 IU / ml (AKL kit "Laboratory of Diagnostic Systems", Russia, the upper limit of 23 IU / ml). As with the Orgentec diagnostika GMBH kit, Germany, the upper limit of 10 IU / ml (AKL level 12, 11 IU / ml), the level of AKL exceeded the upper limit of the reference values by 10-20%. At the same time, there were no clinical and laboratory signs of inflammation (the level of CRP in all samples did not exceed 5 mg / l), there were no signs of cellular and humoral rejection.

According to the survey, a single-vascular coronary lesion was predicted.

34 months after the TS, a coronary angiographic examination revealed an isolated lesion of the anterior interventricular branch (UMF).

In the presented Figure 2 is a coronarogram of the patient J., 17 years old. Stenosis of grade 3 in the proximal third of the LAD (Figure 2, position 3), 34 months after TS.

Revealed according to the study, stenosis of grade 3 in the proximal third of the LAD, required angioplasty with stenting, followed by a good hemodynamic effect. Thus, the prognosis of the development of a single-vascular lesion of the coronary bed was confirmed.

Example 2. In another case, patient T., 23 years old, is considered. Heart transplantation was performed on 02.02.2000. During examination prior to TS, the patient showed significantly elevated levels of AKL (33 and 53 IU / ml). After surgery, they also remained high (26, 25, 44, 25, 23, 27, 35, 26 IU / ml) and never fell below the upper boundary of the reference values (average level of 28.88 ± 7.08 IU / ml) , over 21% of the upper limit of reference values (AKL set "Laboratory of diagnostic systems", Russia). Using the "Orgentec diagnostika GMBH" kit, Germany, similar results were obtained (AKL level 15, 20, 13 IU / ml, average 16 IU / ml). The level of AKL similarly exceeded the upper limit of reference values by more than 21%.

As in all other clinical cases, at the time of assessing the levels of the presented AKL values, the patient had no signs of cellular and humoral rejection, and the level of CRP did not exceed 5 mg / L.

According to the survey, the development of a multivascular, widespread coronary lesion was predicted.

After 12 months on the control coronarography revealed multivascular lesion of the coronary arteries. The anterior interventricular branch is grade 3 stenosis in the proximal third. Envelope branch without pathology. Right coronary artery - two consecutive stenosis in the proximal third. The degree of damage to the coronary arteries required the implementation of repeated nuclear submarines with stenting.

In the presented Figure 3 shows a repeated coronarogram of the patient T., 23 years old. 21 months after heart transplantation. Restenosis in the area of a previously implanted stent, repeated ALL with stenting of the LAD (Figure 3, position 4).

This example demonstrates that if the plasma AKL is exceeded both in the preoperative period and in the first months of more than 21% of the upper limit of the reference values, the development of multivascular damage to the coronary arteries is predicted, which is confirmed by the data of repeated coronarographic studies and repeated angioplastics with stenting.

Among the patients of the second group with multivascular lesions of the coronary arteries, the lesions of 2 or 3 coronary arteries were most frequently encountered, diffuse lesions of the coronary arteries involving the distal bed were revealed, which was a significant limitation for performing adequate myocardial revascularization. All patients of the first group with isolated stenotic lesions underwent angioplasty (APL) of the affected arteries of the transplanted heart. For patients of the second group, with high levels of plasma AKL, adequate myocardial revascularization was possible in less than half.

To control the results, 15 patients were examined in whom the level of AKL did not exceed the upper limit of the reference values. No BCAPS was detected in any of the examined patients (mean AKL level was 18.46 ± 9.78 IU / ml).

Figure 4 shows the plasma AKL levels in heart recipients with isolated coronary artery disease (4 patients, 26 studies, Figure 4, position 5), multivascular coronary artery disease (6 patients, 24 studies, Figure 4, position 6) as well as in patients without signs of coronary artery damage (15 patients, 80 studies, Figure 4, position 7) during the entire observation period.

The groups of patients with single-vessel and multi-vessel coronary artery lesions differed in AKL levels both among themselves (Fig. 1), and with a group of patients without revealed BCAPS (a group of patients with single-vessel damage of coronary arteries and a group of patients without revealed BCAPS - p> 0.001, and a group of patients with multivascular damage to the coronary arteries and a group of patients without revealed BCAPS - p> 0.001).

Example 3. As a clinical example, patient S., 53 years old, is considered with a diagnosis of a condition after TS from 02/20/2001. Prior to the patient's TS, the levels of AKL did not exceed the reference values (13, 22, and 15 IU / ml). In the postoperative period, the picture remained the same, the levels of antibodies to cardiolipin remained normal: 12, 9, 14, 20, 20 (average 15.9 ± 4.7 IU / ml, while there were no clinical and laboratory signs of inflammation (level of SRV in all the samples did not exceed 5 mg / l), there were no signs of cellular and humoral rejection. According to the annual coronary angiographic studies of the patient, coronary lesions were not detected in the patient for the entire observation period.

This example clearly demonstrates that the normal level of antibodies to cardiolipin is not associated with the possibility of developing BCAPS in the long term.

The level of AKL in blood plasma should be recognized as one of the clearest markers associated with the detection of BCAPS, and the only one that allows predicting the prevalence of coronary lesions in the preoperative period and from the first months of monitoring recipients of the heart after surgery and the possibility of adequate myocardial revascularization in this case . In this connection, its diagnostic significance in the pre- and in the early postoperative periods seems extremely high.

Claims (1)

A method for preoperative prediction of single-vessel and multi-vessel stenotic lesions of the coronary graft in recipients of the heart by determining the level of antibodies to cardiolipin in the blood plasma of patients, characterized in that when exceeding the upper boundary of the reference values of the level of antibodies to cardiolipin in blood plasma in at least two studies on 10- 20% predict the development of an isolated, single-vessel stenotic lesion of the coronary arteries after heart transplantation, and if exceeded the upper limit of the reference values of the level of antibodies to cardiolipin in blood plasma in at least two studies more than 21% predict the development of multivascular stenotic lesions of the coronary arteries.

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