RU2745473C1 - Method for predicting the risk of developing repeated remodeling of the left ventricular myocardium within 12 months after surgical treatment of ischemic cardiomyopathy - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: present invention relates to medicine, namely to cardiac surgery, and relates to predicting the risk of developing re-remodeling of the left ventricular myocardium within 12 months after surgical treatment of ischemic cardiomyopathy. For this, invasive coronary angiography and radionuclide equilibrium tomoventriculography with 99mTc-pyrophosphate are performed at rest and against the background of successive intravenous infusions of dobutamine at doses of 5, 10, 15 mcg/kg/min for 5 minutes each. Based on the results obtained, the stress-induced change in the parameters of the ejection fraction and the standard deviation of the phase histogram of the left ventricle of the heart is determined. Then, the prognostic probability of the development of repeated remodeling of the left ventricle of the heart is calculated according to the original formula, and at a value of more than 0.5, a high probability of the development of repeated remodeling of the left ventricle of the heart after surgical treatment of ICMP is predicted.

EFFECT: method provides high predictive accuracy and reproducibility of diagnostics.

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Description

The invention relates to medicine, namely to radionuclide diagnostics in cardiology, and is intended to predict the risk of re-remodeling of the left ventricle of the heart (LV) after surgical treatment of ischemic cardiomyopathy (ICMP) in order to improve the selection of patients for this type of treatment and the choice of tactics for their postoperative period. The method can be used in cardiology departments of medical and diagnostic institutions equipped with radioisotope laboratories.

It is known that coronary heart disease (CHD) remains one of the main causes of death and disability in the world population, as well as one of the main factors in the development of chronic heart failure (CHF) [1]

To designate patients with CHF and IHD in history, the term "ischemic cardiomyopathy" was introduced into clinical practice - a condition characterized by myocardial dysfunction with inadequate perfusion caused by obstructive coronary artery disease [2]. Of particular importance to this nosology is the fact that among patients with various cardiomyopathies, it is precisely patients with ICMP that have the worst prognosis [3]. A number of studies have shown that surgical treatment of this pathology has an advantage over conservative therapy [4, 5]. It may include maximal revascularization, LV cavity reconstruction, and mitral valve repair. However, despite all efforts, up to 30% of patients undergo repeated LV remodeling in the delayed period after surgical treatment of ICMP [6], which is associated with a poor prognosis [7]. In connection with this, there is a need to develop new criteria for selecting patients for surgical correction of ICMP.

Myocardial contractile reserve in the form of a response by increased contractility to inotropic stimulation is a recognized prognostic criterion for the restoration of the contractile function of the heart after surgical treatment of ICMP [8]. It is known that methods based on the identification of the contractile reserve are more specific compared to methods based on the assessment of perfusion in terms of restoration of dysfunctional myocardium after revascularization [9].

A known method for predicting LV myocardial remodeling by determining specific genetic markers [10]. The disadvantage of this method is the high cost and complexity of implementation.

A known method for predicting the unfavorable course of CHF ischemic genesis [11], based on the detection of the level of tissue inhibitor of matrix metalloproteinases in the blood and carrying out an echocardiographic (EchoCG) study of the heart with the calculation of a specific index (CVC). The disadvantage of this method is the high operator dependence of echocardiography, as well as low specificity values (46.7% for CVS, 61.1% for the level of metalloproteinases).

A known method for predicting the risk of developing unfavorable remodeling of the left ventricle of the heart in patients with acute anterior myocardial infarction with ST segment elevation within 6 months from the onset of the disease [12]. The disadvantages of this method is that the examination must be carried out on the first day after myocardial infarction.

None of these methods is aimed at predicting postoperative results in this group of patients.

A known method of carrying out planar radionuclide ventriculography against the background of the introduction of dobutamine at a dose of 10 μg / kg / min 35 patients with ICMP before coronary artery bypass grafting. The investigators found that an increase in LVEF of ≥10% during a stress test predicted an increase in LVEF by> 5% one month after coronary artery bypass grafting with a sensitivity of 67% and a specificity of 93% [13]. The disadvantage of this method is the use of a less accurate planar method of recording the study, as well as the lack of study of the parameters of dyssynchrony.

A known method for determining the contractile reserve of the left ventricle of the heart in patients with ICMP [14]. This method is based on performing radionuclide tomoventriculography (RTVG) of the heart with 99mTc-pyrophosphate at rest and against the background of dobutamine infusion at doses of 5, 10, 15 μg / kg / min for 5 minutes each. The disadvantages of this method is that it does not allow predicting the risk of re-remodeling of the left ventricular myocardium within 12 months after surgical treatment of ischemic cardiomyopathy.

This method is the closest to the claimed technical essence and the achieved result and is chosen as a prototype.

The aim of the invention is to improve the quality of patient selection for surgical treatment of ICMP by identifying those who have an increased risk of re-remodeling of the left ventricle of the heart.

This goal is achieved by performing radionuclide tomoventriculography (RTVG) of the heart with 99mTc-pyrophosphate at rest and against the background of dobutamine infusion at doses of 5, 10, 15 μg / kg / min for 5 minutes each, according to the results of which the value of the stress-induced change in the fraction is determined LV ejection (EF) (LV AFV) and standard deviation of LV phase histogram (PSD) (LV APSD) according to the formula:

ΔP = P ^stress -P ^rest

where ΔP - stress-induced change in the indicator

P ^rest - the value of the indicator at rest

P ^stress - the value of the indicator at the peak of the stress test,

and the number of coronary arteries with atherosclerotic luminal stenosis> 75% (CS> 75%). Further, the likelihood of the development of repeated myocardial remodeling within 12 months after surgical treatment of ICMP is determined according to the formula:

where P is the predictive probability,

e - base of natural logarithm (mathematical constant; e = 2.718),

CS> 75% - the number of coronary arteries with atherogenic stenosis> 75%,

Δ LVEF is a stress-induced change in the left ventricular ejection fraction,

ΔPSD LV - stress-induced change in the standard deviation of the phase histogram of the left ventricle of the heart,

and if the P value is greater than 0.5, a high probability of the development of repeated remodeling of the left ventricular myocardium is predicted within 12 months after surgical treatment of ischemic cardiomyopathy.

The essential features of the invention exhibit new properties in the claimed combination, which leads to the achievement of a new positive effect that does not explicitly follow from the prior art in this field and is not obvious to a person skilled in the art.

An identical set of features was not found in the known solutions according to the data of the patent and scientific-methodical literature.

The proposed method can be used in practical health care as an additional criterion for selecting patients for cardiac surgical treatment of ICMP.

Based on the foregoing, the proposed invention should be considered as corresponding to the conditions of patentability "Novelty", "Inventive level", "Industrial applicability".

The invention will be clear from the following description and the figures suggested thereto.

FIG. 1 shows a polar map of LV mobility and a phase histogram with a PSD index obtained during the study in the patient's state of functional rest (A) and against the background of a stress test (B).

FIG. 2 shows ROC curves obtained in the analysis of LVEF (4), LV ΔPSD (3), CS> 75% (2) and the identified prognostic model (PH) (1), in determining the prognosis of the development of repeated remodeling.

The method is carried out as follows. 24 hours before the study, patients are advised to exclude the use of caffeine-containing beverages, calcium channel blockers and beta-blockers. 30 minutes before the examination, an intravenous catheter is inserted into the subject's cubital vein. Erythrocyte labeling in vivo is produced according to the standard protocol with the introduction of 555-740 mBq Tc ^99m -pyrophosphate (Pirfotech, Diamed, Russia) [15]. The patient is positioned on the diagnostic table of a single-photon emission computed tomograph lying on his back with his hands extended behind his head. The detectors are centered on the region of the heart. The center of the energy window was set at the 99mTc photopeak - 140 keV; the energy window width is symmetrical (20%). The ECG and BP are recorded at rest. Then the RTVG is recorded at rest. After that, a series of sequential infusions of dobutamine at doses of 5, 10, 15 μg / kg / min for 5 minutes each with parallel recording of RTVG is performed through the installed catheter by means of an infusion pump. All recordings are performed in ECG-timed mode. During the administration of each dose of dobutamine, the ECG and blood pressure are monitored. Data processing is carried out in automatic and semi-automatic modes. The indices of volumes, EF and LV intraventricular dyssynchrony - PSD (Fig. 1) are calculated.

Based on the results obtained, the stress-induced change in LVEF and LV PSD is calculated using the formula:

ΔP = P ^stress -P ^rest

where ΔП is a stress-induced change in the indicator

P ^rest - the value of the indicator at rest

P ^stress - the value of the indicator at the peak of the stress test

To obtain a formula that allows predicting the likelihood of re-remodeling of the heart, the study included 30 patients with an established diagnosis of ICMP [16], who were referred for surgical treatment. Before interventional treatment, all patients underwent a complete clinical, laboratory and instrumental examination, and all patients underwent RTVG along with dobutamine administration to assess the contractility of both heart ventricles. In the early postoperative period (7-14 days), all patients underwent echocardiography.

Scintigraphic studies were performed using a Discovery NM / CT 570 s single-photon emission computed tomograph (GE Healthcare, USA) equipped with a gamma camera with CZT detectors.

12 months after surgery, all patients were assessed for their clinical status and cardiac contractility using an echocardiographic method. The criterion for the development of repeated remodeling was an increase in LV CVR or a decrease of ≤10% relative to the early postoperative period [7].

Statistical processing of the results was carried out in the software package STATISTICA v10 and MedCalc 12.1.14.0. The Shapiro-Wilk criterion was used to assess the distribution of quantitative features. Receiver Operating Characteristic Analysis (ROC) was used to determine the diagnostic efficiency of the investigated methods. The informative value of the diagnostic test was determined by assessing the area under the curve - Area Under Curve (AUC), as well as comparing the indicators of sensitivity and specificity. The nonparametric DeLonge test was used to compare the ROC curves. To build a model for predicting the development of repeated remodeling, we used regression analysis in the form of binary logistic regression: odds ratios (OR) and confidence interval (CI) were calculated. Differences were considered statistically significant at p <0.05.

According to univariate logistic regression analysis, LVEF (OR = 0.88; CI 0.8; 0.97; p = 0.008), ΔPSD LV (OR = 1.13; CI 1.03; 1.25; p = 0.005 ), CS> 75% (OR = 4.25; CI 1.57; 11.48; p = 0.001).

Using the regression coefficients of the revealed scintigraphic parameters, an equation was derived to calculate the predictive probability of the development of repeated remodeling in ICMP patients 12 months after surgery:

where P is the predictive probability,

e - base of natural logarithm (mathematical constant; e = 2.718),

CS> 75% - the number of coronary arteries with atrosclerotic stenosis> 75%,

Δ LVEF is a stress-induced change in the left ventricular ejection fraction,

ΔPSD LV - stress-induced change in the standard deviation of the phase histogram of the left ventricle of the heart,

If the P value is greater than 0.5, a high probability of the development of repeated remodeling of the left ventricle of the heart is predicted within 12 months after surgical correction of ICMP.

According to the results of the ROC analysis, LVEF ∆ had a sensitivity of 65% and a specificity of 82% for a cut-off value of ≤4 (AUC = 0.674), CS> 75% showed a sensitivity value of 84% and a specificity of 46% for a value> 2 (AUC = 0.691). ΔPSD LV - sensitivity 87% and specificity 64% for a value> -1 (AUC = 0.727). The logistic model, taking into account all these indicators, had a sensitivity of 87%, a specificity of 82% and AUC = 873, which turned out to be significantly higher than all the indicated indicators taken separately (p <0.05).

Clinical example 1 (LV re-remodeling).

The patient is 61 years old. Diagnosis - ischemic cardiomyopathy, chronic heart failure, functional class III (NYHA). According to echocardiography, LVEF = 30%, LV CSR = 151 ml. According to angiography data, PNA stenosis is 75%, DA1 stenosis is 75%. According to the results of RTVG with dobutamine, LVEF was + 1%, LVPSD +5 degrees. Using the data obtained, the probability value was calculated:

P = 0.84

The obtained value of P = 0.84 allows us to assume at the preoperative stage that this patient will develop repeated LV remodeling within 12 months after the operation.

The patient underwent coronary artery bypass grafting and LV repair. In the early postoperative period, EF and CSR were 36% and 110 ml, respectively. After 12 months, echocardiographic examination revealed no increase in EF and an increase in LV volumes (LVEF = 34%, LV CSR = 115 ml).

Clinical example 2 (LV reverse remodeling).

Patient 60 years old. Diagnosis - ischemic cardiomyopathy, chronic heart failure, functional class III (NYHA). According to echocardiography, LVEF = 32%, LV CSR = 135 ml. According to angiography, stenosis of PNA is 75%, SNA stenosis is 90%. According to the results of RTVG with dobutamine, Δ LVEF was + 11%, ΔPSD LV -3 degrees. Using the data obtained, the probability value was calculated:

P = 0.097

The obtained value of P = 0.097 allows us to assume at the preoperative stage that this patient will not develop repeated LV remodeling within 12 months after the operation.

The patient underwent coronary artery bypass grafting and LV repair. In the early postoperative period, EF and CSR were 32% and 115 ppm, respectively. After 12 months, echocardiographic examination revealed an increase in EF and a decrease in LV volumes (LVEF = 40%, LVEF = 114 ml).

The method proposed as an invention has been tested on 30 patients and allows to increase the accuracy of predicting the likelihood of the development of repeated LV remodeling within 12 months after surgical correction of ICMP

List of used literature

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Claims (7)

A method for predicting the risk of re-remodeling of the left ventricular myocardium after surgical treatment of ischemic cardiomyopathy, which consists in conducting invasive coronary angiography and radionuclide equilibrium tomoventriculography with 99mTc-pyrophosphate at rest and against the background of successive intravenous infusions of dobutamine at doses of 5, 10 kg / kg min for 5 minutes each, characterized in that they determine the stress-induced change in the left ventricular ejection fraction (ΔFVL) and the standard deviation of the phase histogram of the left ventricle (ΔPSDLV), and the prognostic probability of the development of repeated left ventricular remodeling according to the formula

, where P is the predictive probability, e - base of natural logarithm (mathematical constant; e = 2.718), CS> 75% - the number of coronary arteries with atherogenic stenosis> 75%, Δ LVEF is determined by the formula: value of the indicator at the peak of the stress test - the value of the indicator at rest; ΔPSD LV is determined by the formula: the value of the indicator at the peak of the stress test - the value of the indicator at rest; and if the P value is greater than 0.5, a high probability of the development of repeated remodeling of the left ventricular myocardium is predicted within 12 months after surgical treatment of ischemic cardiomyopathy.

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