RU2741195C1 - Method for prediction of urgent cardiovascular complications in acute coronary syndrome in patients with oncological disease in past history - Google Patents

Abstract

FIELD: medicine.SUBSTANCE: invention refers to medicine, particularly to cardiology and can be used for prediction of developing cardiovascular complications in hospital period in acute coronary syndrome in patients with oncological disease in past history. GRACE scores are calculated, NT-proBNP (pg/ml) content is determined on the first day of hospitalization in acute coronary syndrome in patients with oncological disease in the past medical history, at the stage of preparation for treatment, during active treatment or after its completion. Total score "OZ.GRACE - NT-proBNP" is calculated from the constructed logistic regression equation. If the value is more than −0.1667, possible development of urgent cardiovascular complications in the hospital period in acute coronary syndrome in patients with oncological disease in the past history is predicted.EFFECT: method enables predicting development of urgent cardiovascular complications in hospital period in acute coronary syndrome in patients with oncological disease in past history.1 cl, 3 ex, 2 dwg

Description

The invention relates to medicine, namely to cardiology, and can be used to predict the development of urgent cardiovascular complications (CVC) in the hospital period with acute coronary syndrome (ACS) in patients with a history of cancer (OZ).

It is known that the largest contribution among the causes of mortality in the population belongs to cardiovascular diseases, including ischemic heart disease (IHD) and OZ. The high prevalence of coronary artery disease and OZ leads to the emergence of a large number of patients with combined pathology, requiring a special approach to management [1]. Regardless of how long ago the diagnosis of OZ was verified and antitumor therapy was performed, 1.9-4.2% of patients develop ACS [2]. In this case, the maximum risk of exacerbation of ischemic heart disease is observed with the progression of OZ, chemotherapy and radiation therapy, surgical interventions [3]. Iannaccone M. et al (2018) showed that the presence of OZ is a strong independent predictor (LI) and recurrent myocardial infarction (MI) (RR 2.1, 1.8-2.5, p <0.001) in ACS [4 ].

The main cause of hospital mortality in ACS remains the development of urgent CVC. At the same time, the current guidelines for the management of patients with ACS do not provide a clear position in relation to patients with a history of OZ [5, 6].

Currently, various methods, including models and scales, have been proposed for predicting the course of ACS, which make it possible to stratify the risk of complications and LI in patients during the hospital period. However, when developing such methods, the presence of OZ in the anamnesis was not taken into account. Moreover, a history of OZ is usually a criterion for exclusion from studies.

The GRACE scale is most often used to stratify the risk of death and / or recurrent MI from admission to 6 months after discharge. However, this scale assesses only the risk of LI and / or recurrent myocardial infarction, excluding other CVCs in the hospital period.

Various biomarkers are being actively studied to predict the course of ACS. One of the most studied is brain natriuretic peptide (NT-proBNP). NT-proBNP increases in ACS, while the dynamics of its level reflects both the severity of heart failure and is an independent predictor of low survival in patients with ACS both in the immediate and long-term period [7]. At the same time, NT-proBNP level control is used in OZ patients receiving chemotherapy courses in order to assess the risk of development and the severity of cardiotoxicity [8].

However, at present there are no special scales and models for patients with ACS with a history of OZ. The model “GRACE-NGAL - FV” developed by Shalenkova MA, Mikhailova ZD, Klimkin PF, Manyukova ET, Kulikanov SA was used as a prototype. (RU 2567031 C1, 2015), to predict the development of cardiovascular complications of ACS with ST segment elevation (ACS) [9]. In the proposed model, the authors used three variables obtained from logistic regression analysis: GRACE scores, the content of lipocalin associated with neutrophil gelatinase (s-NGAL, ng / ml), and left ventricular ejection fraction (LVEF) (%). The diagnostic significance of this model: AUC = 0.834 (95% CI, 0.708-0.921), p = 0.0001. However, the model is intended for use only in ACS and does not take into account the presence of OZ in the anamnesis.

The aim of the invention is to predict the development of urgent CVC in the hospital period with ACS in patients with a history of OZ.

To solve this goal in patients with ACS with a history of OZ (in preparation for treatment, during the period of active treatment or after its completion), the total indicator is calculated

"OZ: GRACE - NT-proBNP" by substituting the corresponding numerical values: points on the GRACE scale, the level of NT-proBNP (pg / ml) in the blood on the 1st day of hospitalization, into the constructed equation of logistic regression. If the value of the indicator "OZ: GRACE - NT-proBNP" is more than -0.1667, calculated on the 1st day of hospitalization, the likelihood of developing urgent CVC in the hospital period with ACS in patients with a history of OZ increases. The statistical significance of the resulting model is p <0.0001.

The diagnostic efficacy of the proposed method was studied in patients admitted urgently to the regional vascular center with ACS (n = 34) who had a verified OZ in history (in preparation for treatment, during the period of active treatment or after its completion). The average age of the patients was 66.4 ± 7.7 years. On admission, ST-ACS was in 13 patients, non-ST-segment elevation ACS (ST-ACS) - in 21 patients; the number of men (n = 17) and women (n = 17) was equal. The diagnosis of NSTE-ACS / NSTE-ACS was established in accordance with the National Recommendations [5, 6] according to the following criteria: anginal pain more than 20 minutes and less than 24 minutes old, high-sensitivity troponin I more than 0.1 ng / ml and / or ECG criteria NSTE-ACS / NSTE-ACS.

ACS patients (n = 34) had the following OZ localizations: lungs (n = 8), oncohematology (n = 7), mammary glands (n = 5), prostate gland (n = 4), large intestine (n = 3) , uterus (n = 3), melanoma (n = 1), kidney (n = 1), bladder (n = 1), glioblastoma (n = 1). The number of patients with T _1-2 was 50%, T _3-4 - 27%, and in 23% were not classified (patients with hematology and glioblastoma).

The examination and treatment of ACS patients with OZ (n = 34) was carried out in accordance with the current standards and recommendations for the management of patients with NSTE-ACS [5] and NSTE-ACS [6].

In the hospital period, the incidence of urgent CVC and LI was assessed. Based on the literature data [5, 6] and our own observations, the following urgent CVCs were identified: myocardial rupture (hemopericardium), cardiogenic shock, pulmonary edema, stent thrombosis, atrioventricular block of the III degree.

In all ACS patients with OZ (n = 34) on the 1st day of hospitalization: 1) the GRACE scores were calculated using a publicly available calculator presented at https://medicalc.ru/grace; 2) the content of: NT-proBNP (pg / ml) in the blood was determined by the method of one-stage enzyme-linked immunosorbent assay using two types of monoclonal antibodies to NT-proBNP using a set of "Vector-Best" (Novosibirsk), with an assessment of the optical density using a Sunrise spectrophotometer, Tesal, Austria.

During hospitalization, 56% (n = 19) of patients developed urgent CVC on average by 3.2 ± 1.8 days. Moreover, 4 patients had several (> 1) urgent CVCs; in 3 patients, urgent CVC had a recurrent course. 2 (6%) of 34 patients had LI. It should be noted that blood sampling and scoring on the GRACE scale in all ACS patients with OZ were performed before the development of urgent CVC.

When developing the proposed method in patients with ACS with a history of OZ (n = 34), clinical and laboratory parameters (quantitative and qualitative) (n = 46) were analyzed. The choice of variables for inclusion in the regression analysis was carried out taking into account the effect of multicollinearity. The response variable was coded as follows: code "1" (development of urgent SSO), code "0" (without development of urgent SSO). With the development of several urgent CVCs in one patient, or with relapse of the same urgent CVC, the response variable was also assigned the code "1".

Using logistic regression analysis in the ACS group with a history of OZ (n = 34), two significant variables were obtained (GRACE scores and NT-proBNP value). The parameters of logistic regression for predicting the development of urgent CVC in ACS with OZ in the hospital period for significant variables are presented in the table in figure 1, where Hosmer & Lemeshow test (Chi-squared = 6.4389 with 10 DF, P = 0.7771); Percent of cases correctly classified - 85.29%; AUC = 0.951 (95% CI, 0.817-0.996).

It was found that the GRACE scores and the NT-proBNP level were significant predictors of the development of urgent CVC in ACS with a history of OZ in the hospital period. The diagnostic significance of this model exceeded the established level (AUC> 0.70), which allowed it to be considered quite stable (AUC = 0.951 (95% CI, 0.817 - 0.996), p <0.0001).

To construct a logistic regression equation that makes it possible to predict the belonging of a particular object to a particular state, the following formula was used:

Y = a + β ₁ × X ₁ + β ₂ × X ₂ [10],

where Y is the response variable, a is a constant, X ₁ and X ₂ are predictor variables (X ₁ is the number of points on the GRACE scale, X ₂ is the NT-proBNP content (pg / ml)), β1, β ₂ are the coefficients of the corresponding predictor variables.

In the table presented in figure 1, the constant of the logistic regression equation (a), and the coefficients of the predictor variables (β ₁ , β ₂ ) are indicated.

Substituting the corresponding numerical values of the table into this formula, a logistic regression equation was constructed to predict the development of urgent CVOs in ACS with a history of OZ in the hospital period:

Y = -8.87992 + (0.048438 × GRACE score) + (0.0031794 × NT-proBNP value (pg / ml)).

The resulting integral indicator “Y” was named “OZ. GRACE - NT-proBNP ".

To assess the predictive value of the model, the indicator “OZ. GRACE - NT-proBNP "was included in the ROC-analysis, the results of which are presented in figure 2. It was found that when the value of the indicator" OZ. GRACE - NT-proBNP "more than -0.1667, the likelihood of developing urgent CVC increases, and the value less than or equal to -0.1667 is associated with a greater probability of the absence of urgent CVC in ACS with a history of OZ in the hospital period (AUC = 0.951 (95% CI , 0.817 - 0.996), p <0.0001).

Predictive sensitivity of the total indicator “OZ. GRACE - NT-proBNP "was 94.74% (95% CI 74 - 99.9), specificity - 86.67%) (95% CI 59.5-98.3); diagnostic efficiency - 90.71%; the likelihood ratio for a positive test result is 7.11, and for a negative one - 0.061.

The predictive accuracy of this model is 95.1%), which corresponds to the area under the ROC curve. The percentage of total cases predicted correctly was 85.29%.

The results were statistically processed using Statistica Version 12.0 software (StatSoft, USA), MedCalc Version 19.1.7. firm Softwa (Belgium). To identify the parameters associated with the development of adverse events (urgent CVE in ACS with a history of OZ in the hospital period), we used the logistic regression method, followed by the construction of a logistic regression equation based on statistically significant parameters. To determine the optimal ratio of the sensitivity and specificity values of the created prognostic model, ROC (Receiver Operating Characteristic) analysis was performed with the construction of a characteristic curve (ROC-curve) and indicating the area under the curve (AUC - Area Under the Curve). Differences were considered significant at p <0.05.

The proposed method is carried out as follows. Upon admission to patients with ACS with a history of OZ (in preparation for treatment, during active treatment or after its completion):

1) points are calculated on the GRACE scale “manually” or using publicly available calculators (for example, on the website https://medicalc.ru/grace);

2) on the first day of hospitalization, NT-proBNP content (pg / ml) is determined in blood serum by enzyme immunoassay.

The obtained specific values of points on the GRACE scale and the NT-proBNP content (pg / ml) are substituted into the equation:

OZ. GRACE - NT-proBNP = -8.87992 + (0.048438 × GRACE score) + (0.0031794 × NT-proBNP value (pg / ml)).

With the value of the indicator “OZ. GRACE - NT-proBNP "more than -0.1667 predict the possible development of urgent CVC in the hospital period with ACS in patients with a history of OZ.

Specific examples of using the proposed method Example No. 1

Extract from the case history No. 2019-8705. Patient Zh., 63 years old, was inpatient treatment from 03/26/19 to 03/29/19, Transferred to the intensive care unit (ICU) with a ST-ACS clinic for 30 minutes. from an anginal attack from the hematology department for the first time in his life (diagnosis: acute leukemia). A serious condition, clear consciousness, half-sitting position, pale skin, moist, pasty feet. In the lungs, vesicular breathing, single moist rales in the lower parts of the lungs (up to the angle of the shoulder blades), NPV 24 / min (Killip II). Heart sounds are muffled rhythmic, heart rate = pulse = 85 per minute, blood pressure 170/85 mm Hg, oxygen saturation 96%. The abdomen is soft, painless, the liver is not enlarged. ECG - sinus rhythm, T (-) in leads I, II, aVL, VI-6. Troponin I - 0.116 ng / ml (the norm is up to 0.1 ng / ml), in dynamics - 2.11 ng / ml. Diagnosis: IHD: acute anterior non-Q MI.

When calculated on the GRACE scale, values of 124 were obtained, which corresponded to the average risk of death and / or re-MI in the hospital period [6]. NT-proBNP content on admission (1st day) is 3440.22 pg / ml.

The calculation of the indicator “OZ. GRACE - NT-proBNP "by substituting the corresponding values into the resulting formula:

OZ. GRACE - NT-proBNP = -8.87992 + (0.048438 × 124) + (0.0031794 × 3440.22 = 8.0642.

Thus, the calculated indicator “OZ. GRACE - NT-proBNP "was found to be 8.0642, that is, more than -0.1667.

The patient refused to undergo selective coronary angiography (SCG), conservative treatment was carried out in accordance with the current recommendations. On the 3rd day, the patient developed severe shortness of breath with an increasing clinic of pulmonary edema. Despite the ongoing treatment, the condition progressively worsened and LI began (resuscitation measures - within 30 minutes without effect). The conclusion of postmortem examination: ischemic heart disease: acute anterolateral, high lateral non-Q MI. Killip IV. Pulmonary edema, cardiogenic shock, asystole from 29.03.2019, Acute leukemia. Bilateral hydrothorax. Bilateral polysegmental aleukocytic-hemorrhagic pneumonia.

Thus, on the 3rd day of the disease, patient G., 63 years old, with NSTE-ACS and OZ developed urgent CVC (pulmonary edema, cardiogenic shock), which led to LI. The indicator “OZ. GRACE - NT-proBNP ", calculated on the 1st day of the disease, was 8.0642 (more than -0.1667), which indicated a high likelihood of developing urgent CVC in the hospital period with ACS with a history of OZ. This was confirmed by the clinical course of the disease. At the same time, with the standard GRACE assessment (124 points), the risk of death and / or recurrent myocardial infarction in the hospital period was defined as “average”.

Example No. 2

Extract from the case history No. 2019-01957. Patient M., 64 years old, was inpatient treatment from 01/19/19 to 01/29/19, Delivered to the hospital from home with the clinic STE ACS 12 hours after the development of anginal pain syndrome, hospitalized in the ICU. History of MI (2014), right kidney cancer (T ₃ N ₀ M ₀ , condition after surgical treatment, 2010, metastasis to the left lung, 2018). On admission: a serious condition, clear consciousness, normal color skin, dry, no edema, hard breathing in the lungs, no wheezing, NPV 22 / min. (Killip I). Heart sounds are muffled rhythmic, heart rate = pulse = 84 beats. per minute, blood pressure 150/90 mm Hg. The abdomen is soft, painless, the liver is not enlarged. ECG - ST segment elevation in II, III, avF up to 4 mm. Troponin 1-1.5 ng / ml (the norm is up to 0.1 ng / ml). According to Echo-KG (on the 1st day) - hypokinesis of the basal, middle lower, inferior septal, inferolateral segments, LVEF 54%. Diagnosis: ischemic heart disease: acute lower LV MI. When calculated on the GRACE scale, values of 141 points were obtained, which corresponded to a high risk of death and / or recurrent myocardial infarction in the hospital period [5]. The NT-pro BNP content on admission (1 day) is 645.86 pg / ml.

The calculation of the indicator “OZ. GRACE - NT-proBNP "by substituting the corresponding values into the resulting formula:

OZ. GRACE - NT-proBNP = -8.87992 + (0.048438 × 141) + (0.0031794 × 645.86 -0.0033.

Thus, the calculated indicator “OZ. GRACE - NT-proBNP "was found to be 0.0033, which is more than -0.1667.

The treatment was carried out in accordance with the current guidelines. In SCG - acute occlusion of the right coronary artery (RCA), percutaneous coronary intervention (PCI) was performed with the installation of 2 non-drug-eluting stents. On the 4th day, the patient: relapse of anginal pain, the ECG increased ST segment elevation in II, III, avF up to 6 mm. In case of repeated SCG, occlusion of a previously installed stent in the RCA (class IV according to R. Merhran). RCA re-stenting was performed, 1 drug-eluting stent was installed (TIMI III blood flow).

The patient was discharged on the 10th day in a stable condition for further treatment in a sanatorium. Diagnosis at discharge: IHD: acute inferior Q MI with spread to the posterior-basal and lateral parts of the LV. Killip I. RCA stenting from 01/19/19, RCA stent thrombosis from 01/22/19, RCA stenting from 01/22/19, CHF II A, II FC. Cancer of the right kidney with metastasis to the left lung.

Thus, in patient M., 63 years old, the course of ACS was complicated by stent thrombosis on the 4th day of the disease. The indicator “OZ. GRACE - NT-proBNP ", calculated on the 1st day of the disease, was 0.0033 (more than -0.1667), which indicated a high likelihood of developing urgent CVC in the hospital period with ACS with a history of OZ. At the standard GRACE assessment (141 points), the risk of death and / or recurrent MI in the hospital period was defined as “high”.

Example No. 3

Extract from the case history No. 2019-08927. Patient M., 53 years old, was inpatient treatment from 04/02/19 to 04/12/19, was admitted to the hospital urgently with the NSTE ACS clinic 3 hours after the onset of a prolonged angina attack. History of chronic myeloid leukemia, chronic stage, during imatinib therapy. On admission: a serious condition, clear consciousness, normal color of the skin, clean, dry. In the lungs, vesicular breathing, weakened in the lower sections, no wheezing, NPV 18 per minute. (Killip I). Heart sounds are muffled rhythmic, heart rate = pulse = 68 beats / min, blood pressure 160/80 mm Hg. On the ECG - T (-) in I, III, aVF. Troponin I - 0.255 ng / ml (the norm is up to 0.1 ng / ml). Diagnosis: ischemic heart disease: acute inferior non-Q MI. When calculated on the GRACE scale, values of 109 points were obtained, which corresponded to the average risk of death and / or recurrent myocardial infarction in the hospital period [7]. The NT-proBNP content on admission was 303.82 pg / ml.

The calculation of the indicator “OZ. GRACE - NT-proBNP "by substituting the corresponding values into the resulting formula:

OZ. GRACE - NT-proBNP = -8.87992 + (0.048438 × 109) + (0.0031794 × 303.82 = -2.6342.

Thus, the calculated indicator “OZ. GRACE - NT-proBNP "was found to be -2.6342, which is less than -0.1667.

The treatment was carried out in accordance with the current guidelines. In SCG - subtotal stenosis of RCA of the proximal, middle, and distal third, PCI with stenting was performed (4 stents without drug coverage).

The patient was discharged on the 10th day in a stable condition for further treatment in a sanatorium. Diagnosis at discharge: IHD: acute inferior non-Q MI. RCA stenting dated 04/03/19, CHF PA (II FC) Chronic myeloid leukemia, chronic stage, during imatinib therapy.

Thus, in patient M., 53 years old, the hospital ACS period proceeded without the development of urgent CVC. The indicator “OZ. GRACE - NT-proBNP ", calculated on the 1st day of the disease, was -2.6342 (less than -0.1667), which indicated a low likelihood of developing urgent CVC in the hospital period with ACS with a history of OZ. This was confirmed by the clinical course of the disease. At the same time, the average risk of death and / or recurrent myocardial infarction in the hospital period was determined with the standard GRACE assessment (109 points).

INFORMATION SOURCES

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2. Luboyatnikova E.C., Duplyakov D.V. Acute coronary syndrome in patients with malignant neoplasms. Russian journal of cardiology. 2017; 3 (143): 140-144, doi: 10.15829 / 1560-4071-2017-3-140-144.

3. Balluzek M.F., Ionova A.K. Cardio-oncology in treatment and rehabilitation programs for cancer patients. Russian journal of cardiology. 2014; 5 (109): 75-80, doi: 10.15829 / 1560-4071-2014-5-75-80.

4. Iannaccone M., DAscenzo F., Vadala P., et al. Prevalence and outcome of patients with cancer and acute coronary syndrome undergoing percutaneous coronary intervention: a BleeMACS substudy. Eur Heart J Acute Cardiovasc Care. 2018; 7 (7): 631-638, doi: 10.1177 / 2048872617706501.

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8. Lopez-Sendon J., Alvarez-Ortega C, Zamora Aunon P. et al. Classification, prevalence, and outcomes of anticancer therapy-induced cardiotoxicity: the CARDIOTOX registry. Eur Heart J. 2020, doi: 10.1093 / eurheartj / ehaa006

9. Shalenkova M.A., Mikhailova Z.D., Klimkin P.F., Kulikanov S.A., Pogrebetskaya V.A. A method for predicting the development of cardiovascular complications of acute coronary syndrome with ST-segment elevation: patent RU 2567031 C1 Russia 2015.

10. StatSoft, Inc. (2012). Electronic textbook on statistics. Moscow, StatSoft. WEB: http://www.statsoft.ru/home/textbookydefault.htm.

Claims (1)

A method for predicting urgent cardiovascular complications in acute coronary syndrome in patients with a history of oncological disease, including calculating GRACE scores upon admission, determining the NT-proBNP content (pg / ml) in the blood on the 1st day of hospitalization, characterized by the fact that that in patients with acute coronary syndrome with a history of oncological disease, the total indicator "OZ.GRACE - NT-proBNP" is determined by substituting the obtained numerical values into the equation of logistic regression OZ. GRACE - NT-proBNP = -8.87992 + (0.048438 × points on the GRACE scale) + (0.0031794 × NT-proBNP value (pg / ml)), and with the value of OZ.GRACE - NT-proBNP »More than -0.1667 predict the possible development of urgent cardiovascular complications in the hospital period with acute coronary syndrome in patients with a history of oncological disease.

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