RU2848905C1 - Method for predicting mortality in patients with myocardial infarction-associated cardiac shock during two-year follow-up period - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to cardiology and can be used to predict mortality in patients with myocardial infarction-associated cardiogenic shock (MI CS) over a two-year observation period. When a patient develops MI CS, the absolute neutrophil count, absolute lymphocyte count, absolute monocyte count, and CK-MB activity are determined in the peripheral blood, and then the modified systemic inflammatory response index SIRI-CK-MB is determined using a special formula. A SIRI-CK-MB value of 133.9 or higher predicts a high risk of mortality within two years after the development of MI CS.

EFFECT: method allows predicting mortality in patients with MI CS during a two-year observation period by determining the value of the modified systemic inflammatory response index.

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Description

The invention relates to medicine, namely to cardiology, and can be used to predict two-year mortality in patients with myocardial infarction-associated cardiogenic shock (MI) at stage C according to the classification of the American Society of Cardiovascular Angiography and Intervention (SCAI).

Cardiogenic shock (CS) is one of the most serious complications of myocardial infarction (MI). Decreased cardiac output in CS is accompanied by severe progressive hypoperfusion of internal organs and can ultimately lead to multiple organ dysfunction. Mortality rate in CS exceeds 40%. Mortality risk is determined by the clinical profile of patients; however, standard mortality prediction scales are not always applicable in patients with CS [1]. The latest CS staging system was proposed in 2019 by the American Society of Cardiovascular Angiography and Intervention (SCAI) and includes a 5-stage classification of CS from A to E, where stage A represents a condition with a risk of developing CS, and stage E represents the stage of “extreme” CS with circulatory collapse. Stage C is considered the stage of “classic CS,” at which internal organ hypoperfusion develops [2]. The risk of in-hospital mortality increases progressively from stage A to stage E. However, it remains possible that, in addition to the stage of MI according to the SCAI scale, at which the patient is in a certain time period, the decisive prognostic factor may be the heterogeneity of MI itself from a pathophysiological point of view, and therefore there remains a need to search for a new approach to determine the prognosis, especially in patients at stage C, which is most often the stage at which patients with MI are admitted to the intensive care unit [3].

It has been shown that the systemic inflammatory response, caused by both the primary damage to cardiac tissue during infarction and progressive multiple organ failure, plays a significant role in the development and progression of myocardial infarction [4]. Recently, systemic inflammation indices based on complete blood count results have attracted the attention of researchers as prognostic biomarkers: their determination is relatively inexpensive, simple to perform, and their calculation is intuitive [5].

The systemic inflammation response index (SIRI) is determined based on the levels of monocytes, neutrophils, and lymphocytes. Neutrophils are among the first to be activated during inflammation and produce a wide range of biologically active mediators and reactive oxygen species. Monocytes are the circulating precursors of tissue macrophages, the main phagocytic cells, which are also capable of producing cytokines. Lymphocytes, the cells of the adaptive immune system, are the main regulators of inflammation and the immune response [6]. Calculating SIRI thus provides a comprehensive assessment of key cellular mediators of inflammation. However, this indicator is nonspecific and can increase with any type of inflammatory response, regardless of its etiology.

A known method for predicting five-year mortality in patients after ST-segment elevation MI involves determining the SIRI index at the time of the patient's admission to hospital. SIRI values greater than the 75th quartile predict an increased risk of mortality in patients within 5 years [7].

This method is the closest to the declared one in terms of technical essence and the achieved result and was chosen as a prototype.

A drawback of this method is that SIRI is a non-specific indicator for patients with MI. Therefore, it is important to study the feasibility of using a modified SIRI index that takes into account, along with the absolute immune cell count, the activity of the creatine phosphokinase fraction MB (SIRI-CPK-MB) to predict mortality in patients with MI over a two-year follow-up period.

The aim of the invention is to improve the accuracy of predicting mortality in patients with myocardial infarction within two years after the development of myocardial infarction.

The stated goal is achieved by determining the absolute content of neutrophils, absolute content of lymphocytes, absolute content of monocytes in the peripheral blood of a patient with the development of myocardial infarction, as key cellular mediators of inflammation development, as well as determining the activity of CPK-MB as a biomarker of the size of myocardial damage, and then determining the modified index of the systemic inflammatory response SIRI-CPK-MB using the formula

SIRI-KFK-MB = NEU × MON × KFK-MB ÷ LYMPH

where SIRI-CPK-MB is the modified systemic inflammatory response index,

NEU - absolute neutrophil count,

MON - absolute monocyte count,

CPK-MB - activity of the MB fraction of creatine phosphokinase,

LYMPH - absolute lymphocyte count,

and with a SIRI-CK-MB value of 133.9 or more, a high risk of patient mortality is predicted within two years after the development of myocardial infarction.

What is new in the proposed method is that, during the development of MI, the activity of the MB fraction of creatine phosphokinase is additionally determined, and then the modified systemic inflammatory response index SIRI-CPK-MB is determined using the formula

SIRI-KFK-MB = NEU × MON × KFK-MB ÷ LYMPH,

where SIRI-CPK-MB is the modified systemic inflammatory response index,

NEU - absolute neutrophil count,

MON - absolute monocyte count,

CPK-MB - activity of the MB fraction of creatine phosphokinase,

LYMPH - absolute lymphocyte count,

and with a SIRI-CK-MB value of 133.9 or more, a high risk of patient mortality is predicted within two years after the development of myocardial infarction.

The essential features of the proposed invention have demonstrated in the claimed set new properties that do not clearly follow from the level of technology in this area and are not obvious to a specialist.

An identical set of features was not found in the patent and scientific medical literature.

The method proposed as an invention can be used in practical healthcare to improve the accuracy of predicting mortality in patients with myocardial infarction during a two-year observation period.

Based on the above, the proposed method should be considered as complying with the patentability conditions of “Novelty”, “Inventive step”, “Industrial applicability”.

The invention will be understood from the following description and the accompanying figures. Fig. 1 shows survival curves obtained using the Kaplan-Meier method: 1 - for patients with MI bypass and SIRI-CK-MB<133.9 and 2 - for patients with MI bypass and SIRI-CK-MB≥133.9.

The method is carried out as follows.

The study included 44 patients diagnosed with stage C coronary artery bypass graft infarction (CAI) according to the American Society of Cardiovascular Angiography and Intervention (SCAI) classification. Patient records were retrospectively analyzed, including clinical, anamnestic, laboratory, and instrumental data. Mortality was assessed at 1, 6, 12, and 24 months. All patients signed informed consent for the processing of their medical data upon hospital admission. The study protocol was approved by the Biomedical Ethics Committee of the Research Institute of Cardiology (Protocol No. 266 dated May 22, 2024).

In the development of MI in patients with CAD, the absolute content of neutrophils, absolute content of lymphocytes, absolute content of monocytes, concentration of CPK-MB were determined in the peripheral blood and, based on the results of the studies, the SIRI-CPK-MB index was determined using the formula

SIRI-KFK-MB = NEU × MON × KFK-MB ÷ LYMPH

where SIRI-CPK-MB is the modified systemic inflammatory response index,

NEU - absolute neutrophil count,

MON - absolute monocyte count,

CPK-MB - activity of the MB fraction of creatine phosphokinase,

LYMPH - absolute lymphocyte count

Mortality in the overall group of patients with MI was 20.4% after 1 month; 25% after 6 months; 31.8% after 1 year and 43.2% after 2 years of follow-up. High values of the SIRI-CK-MB index, based on the absolute counts of monocytes, neutrophils, and lymphocytes, as well as CK-MB concentrations, were associated with patient mortality at 1 month (104.7 [43.8; 346.1] in survivors vs. 269.0 [154.0; 526.6] in deceased patients, p=0.023), 6 months (104.7 [43.8; 346.1] in survivors vs. 260.1 [138.3; 526.7] in deceased patients, p=0.046), and 2 years of follow-up (92.8 [43.8; 254.5] in survivors vs. 260.1 [117.4; 803.6] in deceased patients, p=0.028). A ROC analysis was performed, according to which a SIRI-CK-MB index value equal to or greater than 133.9 predicted a high risk of patient mortality (AUC 0.695; sensitivity 73.7%; specificity 72.0%; p=0.028). Pearson's chi-square test with Yates' correction was applied, according to which SIRI-CK-MB values equal to or greater than 133.9 were associated with mortality in patients diagnosed with stage C CABG MI (p=0.007). Survival curves were constructed using the Kaplan-Meier method (Fig. 1) and the log-rank test was performed. Patients with SIRI-CK-MB≥133.9 had a higher mortality rate during two years of follow-up compared with patients with SIRI-CK-MB<133.9, according to the log-rank test (p=0.001). Thus, SIRI-CK-MB can be used to predict mortality during a two-year follow-up period in patients with stage C MI according to the American Society of Cardiovascular Angiography and Intervention (SCAI) classification.

Below are 2 clinical examples of the proposed method.

Example 1

Patient K., 60 years old, was admitted urgently to the emergency cardiology department.

Diagnosis: coronary artery disease: acute recurrent anterior Q-MI with ST segment elevation from 09/02/20. Post-infarction cardiosclerosis 2012.

The patient developed myocardial infarction, stage C according to the SCAI scale.

Objective: pain-to-door time: 87 min; door-to-balloon time: 54 min; Glasgow Coma Scale score: 15; systolic blood pressure on admission: 113 mmHg; diastolic blood pressure: 79 mmHg; mean arterial pressure: 96 mmHg; heart rate: 64 beats/min; respiratory rate: 16 breaths/min; central venous pressure: 5 cm H2O; vasoactive inotropic index: 10.

In the development of MI in a patient with CA, the absolute neutrophil count, absolute monocyte count, and absolute lymphocyte count were determined. The following results were obtained: neutrophils: 5.67×10 ⁹ /l; monocytes: 0.95×10 ⁹ /l; lymphocytes: 2.61×10 ⁹ /l. The concentration of CK-MB was determined: 16.9 U/l.

Based on the results of the blood tests, the patient's SIRI-CPK-MB index was determined to be 34.81 (<133.9).

Upon follow-up at 1 month, 6 months, 1 year, and 2 years, the patient is alive.

Example 2

Patient P., 69 years old, was admitted urgently to the emergency cardiology department.

Diagnosis: coronary artery disease: acute recurrent anterior Q-MI with ST segment elevation from November 30, 2020. Post-infarction cardiosclerosis of unspecified duration.

The patient developed myocardial infarction, stage C according to the SCAI scale.

Objective: pain-to-door time: 540 min; door-to-balloon time: 70 min; Glasgow Coma Scale score: 15; systolic blood pressure on admission: 108 mmHg; diastolic blood pressure: 76 mmHg; mean arterial pressure: 87 mmHg; heart rate: 110 beats/min; respiratory rate: 18 breaths/min; central venous pressure: 7 cm H2O; vasoactive inotropic index: 10.

In the development of MI in a patient with CA, the absolute neutrophil count, absolute monocyte count, and absolute lymphocyte count were determined. The following results were obtained: neutrophils: 7.92×10 ⁹ /l; monocytes: 0.95×10 ⁹ /l; lymphocytes: 2.03×10 ⁹ /l. The concentration of CK-MB was determined: 218 U/l.

Based on the results of the blood tests, the patient's SIRI-CPK-MB index was determined to be 808.8 (>133.9).

At follow-up at 1 month, 6 months, and 1 year, the patient was alive. At the 2-year follow-up, the patient was declared dead.

The method proposed as an invention has been tested on 44 patients and improves the accuracy of mortality prediction during a two-year observation period in patients with myocardial infarction.

Sources of information:

1. Jentzer J.C. Understanding Cardiogenic Shock Severity and Mortality Risk Assessment // Circ Heart Fail. 2020; 13(9): e007568.

doi: 10.1161/CIRCHEARTFAILURE.120.007568.

2. Baran D.A., Grines C.L., Bailey S., et al. SCAI clinical expert consensus statement on the classification of cardiogenic shock: This document was endorsed by the American College of Cardiology (ACC), the American Heart Association (AHA), the Society of Critical Care Medicine (SCCM), and the Society of Thoracic Surgeons (STS) in April 2019 // Catheter Cardiovasc Interv. 2019; 94(1): 29-37.

doi: 10.1002/ccd.28329.

3. Dil S., Kercheva M., Panteleev O., et al. Myocardial Infarction-Associated Shock: A Comprehensive Analysis of Phenotypes, SCAI Classification, and Outcome Assessment // Medicina. 2025; 61(1): 103.

doi: 10.3390/medicina61010103.

4. Dettling A., Weimann J., Sundermeyer J., et al. Association of systemic inflammation with shock severity, 30-day mortality, and therapy response in patients with cardiogenic shock // Clin Res Cardiol. 2024; 113(2): 324-335.

doi:10.1007/s00392-023-02336-8.

5. Yang Y., Xu Y., Liu S., et al. The systemic inflammation indexes predict all-cause mortality in peritoneal dialysis patients // Ren Fail. 2023; 45(1): 2160348.

doi: 10.1080/0886022X.2022.2160348.

6. Ma M., Wu K., Sun T., et al. Impacts of systemic inflammation response index on the prognosis of patients with ischemic heart failure after percutaneous coronary intervention // Front Immunol. 2024; 15: 1324890.

doi: 10.3389/fimmu.2024.1324890.

7. Marchi F., Pylypiv N., Parlanti A., et al. Systemic Immune-Inflammation Index and Systemic Inflammatory Response Index as Predictors of Mortality in ST-Elevation Myocardial Infarction // J Clin Med. 2024; 13(5): 1256.

doi: 10.3390/jcm13051256.

Claims (8)

A method for predicting mortality in patients with myocardial infarction-associated cardiogenic shock over a two-year observation period, which consists in determining the absolute neutrophil count, absolute monocyte count, and absolute lymphocyte count in the peripheral blood of a patient with the development of myocardial infarction-associated shock, characterized in that the activity of the MB fraction of creatine phosphokinase is additionally determined, and then the modified systemic inflammatory response index SIRI-CK-MB is determined using the formula SIRI-KFK-MB = NEU × MON × KFK-MB / LYMPH, where SIRI-CPK-MB is the modified systemic inflammatory response index, NEU – absolute neutrophil count, MON – absolute monocyte count, CPK-MB – activity of the MB fraction of creatine phosphokinase, LYMPH – absolute lymphocyte count, and with a SIRI-CK-MB value of 133.9 or more, a high risk of patient mortality is predicted within two years after the development of myocardial infarction-associated cardiogenic shock.