RU2811654C1 - Method for preoperative assessment of likelihood of early residual pulmonary hypertension after pulmonary endarterectomy - Google Patents

Abstract

FIELD: medicine; cardiovascular surgery.

SUBSTANCE: proposed invention can be used for preoperative assessment of the likelihood of early residual pulmonary hypertension after pulmonary endarterectomy. The patient’s body mass index is determined, whether patient’s blood group belongs to A (II) is determined, the patient’s expiratory reserve volume, minute respiratory volume and bronchopulmonary resistance are measured using body plethysmography, and the left ventricular ejection fraction is determined using transthoracic echocardiography. Using the obtained indicators, the probability of early residual pulmonary hypertension after pulmonary endarterectomy is determined according to the given formula.

EFFECT: proposed method makes it possible to optimize patient management tactics by correcting modifiable risk factors for early residual pulmonary hypertension before a planned operation in individuals with a high probability of its development by assessing the totality of the most significant indicators.

1 cl, 1 dwg, 3 tbl, 2 ex

Description

Field of technology.

The invention relates to medicine, namely to cardiovascular surgery. A method for preoperative assessment of the likelihood of early residual pulmonary hypertension after pulmonary endarterectomy is used to predict residual pulmonary hypertension in the postoperative period in patients with chronic thromboembolic pulmonary hypertension. Patients with verified chronic thromboembolic pulmonary hypertension aged 18 years and older who are planning to undergo pulmonary endarterectomy undergo anamnesis, echocardiographic, laboratory and spirometric studies before surgery.

Early residual pulmonary hypertension is postthromboembolic pulmonary hypertension, detected in the period from the first day after pulmonary endarterectomy to 365 days.

Chronic thromboembolic pulmonary hypertension is a potentially curable form of pulmonary hypertension; with timely and successfully performed surgical treatment - pulmonary endarterectomy, which retains the status of the “gold standard” in the treatment of patients, with timely and successfully performed pulmonary endarterectomy, the pressure in the pulmonary artery can approach physiological values . Despite careful selection of patients by experienced specialists, some of them still have high mean pulmonary pressure after surgery, which is referred to as residual pulmonary hypertension. According to various sources, residual pulmonary hypertension (RPH) develops within 12 months after surgical treatment in 20–35% of patients and has a leading role among the causes of long-term mortality in people with chronic thromboembolic pulmonary hypertension. It is obvious that the development of residual pulmonary hypertension depends on many factors. But at the same time, it is well known that the progression of pulmonary hypertension occurs as the duration of post-embolic damage to the branches of the pulmonary artery increases, and prolonged increased pressure in the pulmonary artery system leads to morphological restructuring of the vessels of the pulmonary tissue, which in the later stages perpetuates changes in the vascular bed, making them irreversible . Despite the 2022 European Society of Cardiology Guidelines on pulmonary hypertension, the diagnosis, treatment and especially prevention of residual pulmonary hypertension after pulmonary endarterectomy are still poorly understood. In this regard, it is of interest to identify early prognostic markers of early residual pulmonary hypertension after pulmonary endarterectomy in patients with chronic thromboembolic pulmonary hypertension to improve the effectiveness of surgical treatment.

Thus, preoperative assessment of the likelihood of early residual pulmonary hypertension after pulmonary endarterectomy allows optimizing patient management tactics by correcting modifiable risk factors for early residual pulmonary hypertension before the planned operation in individuals with a high probability of developing it in the postoperative period.

The most accurate method for diagnosing both pulmonary hypertension and residual pulmonary hypertension is tensiometry - determination of hemodynamic parameters (mean pulmonary artery pressure ≥ 25 mm Hg; pulmonary artery wedge pressure ≤ 15 mm Hg; pulmonary vascular resistance > 3 Wood units) obtained during catheterization of the right heart. The method is invasive, and in everyday clinical work strong indications are needed for right heart catheterization. In addition, the method has limited availability (it is used only in large specialized medical centers). A less accurate method for diagnosing both pulmonary hypertension and residual pulmonary hypertension is the determination of systolic and mean pulmonary artery pressures using transthoracic echocardiography, which is currently recommended and used as screening. It should be emphasized that transthoracic echocardiography in patients with chronic thromboembolic pulmonary hypertension is often even less informative than in the general population, since they have obesity, chronic lung diseases, and severe tachycardia, which significantly complicate the visualization of cardiac structures.

It should be noted that both tensiometry and transthoracic echocardiography do not allow us to determine in advance, before pulmonary endarterectomy, the likelihood of developing early residual pulmonary hypertension in the postoperative period.

State of the art.

The prior art knows a method for assessing the probability of death in patients with pulmonary embolism who are in the hospital (patent RU 2565093), which consists in taking anamnesis, clinical and echocardiographic examination of patients 18 years of age and older who are in the hospital. This takes into account: mode; fact of presence/absence of lung diseases; the presence/absence of chronic venous insufficiency (CVI); right ventricular systolic pressure (RVP) >36 mm Hg. according to Echo-CG data; the presence/absence of the cor pulmonale symptom complex; the presence/absence of right atrium (RA) dilatation; the presence/absence of obesity; the presence/absence of fluid in the pericardium not associated with an infectious process; the presence/absence of right ventricle (RV) dilatation; post-infarction cardiosclerosis (PICS) of the left ventricle. Based on the data obtained, the probability of death in patients with the development of pulmonary embolism is assessed using an original regression equation. Moreover, if an indicator >0.55 is obtained, the patient has a high probability of death. The method makes it possible to identify a group of patients who need the widest possible range of comprehensive preventive measures regarding pulmonary embolism in order to prevent death during its development.

There is a known method for assessing the probability of parietal thrombosis of the right chambers of the heart - the right atrium and the right ventricle (patent RU2488347) which consists in taking a history, clinical and echocardiographic examination of patients 18 years of age and older. When assessing the likelihood of thrombosis, the following are taken into account: the patient’s height, body weight, the presence/absence of an inflammatory process in the patient’s body, the presence/absence of diabetes mellitus, the presence of fluid in the pericardium, dilatation of the right atrium, the thickness of the wall of the right ventricle in millimeters, the presence of signs of post-infarction cardiosclerosis of the apex of the left ventricle . Based on the data obtained, the probability of the presence of mural thrombus formation/mural thrombosis in the right parts of the heart is assessed. The method makes it possible to improve the diagnosis of thrombus formation in the right chambers of the heart in adults and to identify a group at high risk of having blood clots in the right chambers of the heart that require urgent preventive measures to prevent thromboembolism in the pulmonary artery and death.

There is also a known method for assessing the likelihood of pulmonary embolism from the right atrial appendage in adult patients (patent RU 2677013), which consists in taking into account the presence of chronic heart failure, atrial fibrillation, ascites, treatment of other diseases with anticoagulants, post-infarction cardiosclerosis or myocardial infarction during the current hospitalization . The likelihood of pulmonary embolism from the right atrial appendage is assessed. Depending on the value of the probability indicator, patients are classified into a group with a high probability of pulmonary embolism from the right atrial appendage or a group with a low probability. The method makes it possible to improve the assessment of the probability of pulmonary embolism from the right atrial appendage, to determine the group of patients who need adequate preventive measures to prevent thromboembolism in the pulmonary artery and death by assessing a set of the most significant indicators.

The disadvantage of these analogues from the claimed method is that similar methods used predictors of death, the likelihood of parietal thrombosis of the right chambers of the heart and the likelihood of pulmonary embolism from the right atrial appendage in adult patients with pulmonary embolism. Moreover, the claimed method uses predictors of residual pulmonary hypertension after pulmonary endarterectomy in patients with chronic thromboembolic pulmonary hypertension. Similar methods cannot be used to assess the likelihood of early residual pulmonary hypertension after pulmonary endarterectomy in patients with chronic thromboembolic pulmonary hypertension.

In addition, unlike analogues, the use of the claimed method is possible when performing pulmonary endarterectomy.

Disclosure of the invention.

The objective of the invention is to provide early prevention of the development of early residual pulmonary hypertension in patients.

The technical result consists in the possibility of early diagnosis of the development of residual pulmonary hypertension after pulmonary endarterectomy in patients with chronic thromboembolic pulmonary hypertension. Also, the technical result is the ability to identify patients with a high or low probability of early residual pulmonary hypertension in the postoperative period. In addition, the technical result consists in improving the well-being of patients after pulmonary endarterectomy in patients.

The essence of the proposed method is that the patient’s body mass index and the presence or absence of the patient’s blood group A (II) are determined, the patient’s expiratory reserve volume is measured using body plethysmography, the minute volume of respiration is measured using body plethysmography, and the ejection fraction of the left ventricle is determined at using transthoracic echocardiography. Using body plethysmography, bronchopulmonary resistance is determined. The likelihood of early residual pulmonary hypertension after pulmonary endarterectomy is determined using the function:

Z= α+β ₁ X ₁ +β ₂ X ₂ +β ₃ X ₃ +β ₄ X ₄ +β ₅ X ₅ +β ₆ X ₆ +β ₇ X ₇ ,

Where:

α is the free term of the equation,

α = (-8.651);

X ₁ - body mass index - measured in kg/m²;

X ₂ - belonging to blood group A (II);

X ₃ - the value of the international normalized ratio upon admission;

X ₄ - reserve expiratory volume according to body plethysmography;

X ₅ - minute volume of breathing according to body plethysmography;

X ₆ - left ventricular ejection fraction according to transthoracic echocardiography - measured as a percentage;

X ₇ - bronchopulmonary resistance according to body plethysmography;

β_1,β_2,β_3,β_4,β_5,β_6,β₇- coefficients of variables X₁, X₂, X₃, X₄, X₅, X₆, X_7, having meanings:

β ₁ = (-0.126);

β ₂ = (-2.823);

β ₃ = 0.914;

β ₄ = 1.654;

β ₅ = 0.170;

β ₆ = 0.090;

β ₇ = 3.285,

further, the preoperative probability of early residual pulmonary hypertension after pulmonary endarterectomy is determined:

$$P=\frac{e^Z}{1+e^Z}$$ , Where:

P - probability of early residual pulmonary hypertension after pulmonary endarterectomy;

z - calculated regression function;

e is the base of the natural logarithm (e=2.7183).

If the P value is ≥ 0.409, a patient before a planned pulmonary endarterectomy is diagnosed with a high probability of early residual pulmonary hypertension in the postoperative period; if P < 0.409, a low probability of early residual pulmonary hypertension in the postoperative period is diagnosed.

On the basis of the Federal State Budgetary Institution "National Medical Research Center named after. ak. E.N. Meshalkin" of the Ministry of Health of Russia in patients with chronic thromboembolic pulmonary hypertension selected for pulmonary endarterectomy from 2006 to 2019, the results of studies immediately before and after surgery were analyzed. The study group consisted of 353 patients aged from 19 to 77 years. The contribution of known risk factors for chronic thromboembolic pulmonary hypertension and pulmonary embolism, as well as a number of clinical, laboratory and instrumental parameters in the development of residual pulmonary hypertension, was analyzed. Based on the data obtained, using the logistic regression method, a method for preoperative assessment of the probability of early residual pulmonary hypertension after pulmonary endarterectomy was determined. It included 7 indicators that can be determined during a hospital examination: body mass index, blood group A (II) according to the AB0 system, the value of the international normalized ratio upon admission, expiratory reserve volume according to body plethysmography, minute respiratory volume according to body plethysmography, left ventricular ejection fraction according to transthoracic echocardiography, bronchopulmonary resistance according to body plethysmography. The proposed method assesses the likelihood of early residual pulmonary hypertension after pulmonary endarterectomy.

The coefficients of the logistic regression equation are presented in Table 1.

Table 1 Regression function coefficients Index Coefficient χ ²
Walda Significance level achieved OSH 95% CI for OR Constant -8.651 4,806 0.028 <0.001 X ₁ (body mass index) -0.126 5,468 0.019 0.881 [0.793; 0.980] X ₂ (blood type A (II)) -2.823 13,210 <0.001 0.059 [0.013; 0.272] X ₃ (international normalized ratio at admission) 0.914 3,907 0.048 2,495 [1.008; 6.178] X ₄ (expiratory reserve volume) 1.654 4.775 0.029 5,230 [1,186; 7.068] X ₅ (minute breathing volume) 0.170 5,069 0.024 1.185 [1.022; 1.375] X ₆ (left ventricular ejection fraction) 0.090 4.437 0.035 1.095 [1.006; 1.191] X ₇ (bronchial resistance) 3.285 11,216 0.001 26,722 [3.907; 32.771] Note:
The significance of the model is p<0.001.
Percentage of correct classification (Percent Concordant) - 94.8;
Nagelkerk's R2 value is 0.836.
The value of the Hosmer-Lemeshow goodness-of-fit test is χ2=6.331, df=8, p=0.610.

Preoperative assessment of the likelihood of early residual pulmonary hypertension after pulmonary endarterectomy is determined as follows.

At the first stage, the value of the function Z(x) is determined using the formula:

Z= α+β ₁ X ₁ +β ₂ X ₂ +β ₃ X ₃ +β ₄ X ₄ +β ₅ X ₅ +β ₆ X ₆ +β ₇ X ₇ ,

Where:

α is the free term of the equation,

α = (-8.651);

X ₁ - body mass index - measured in kg/m²;

X ₂ - belonging to blood group A (II) according to the AB0 system - presence/absence;

X ₃ - the value of the international normalized ratio upon admission - measured in units;

X ₄ - reserve volume of exhalation according to body plethysmography - measured in liters;

X ₅ - minute breathing volume according to body plethysmography - measured in l/min;

X ₆ - left ventricular ejection fraction according to transthoracic echocardiography - measured as a percentage;

X ₇ - bronchopulmonary resistance according to body plethysmography - measured in kPa*s.

β_1,β_2,β_3,β_4,β_5,β_6,β₇- coefficients of variables X₁, X₂, X₃, X₄, X₅, X₆, X₇, having meanings:

β ₁ = (-0.126);

β ₂ = (-2.823);

β ₃ = 0.914;

β ₄ = 1.654;

β ₅ = 0.170;

β ₆ = 0.090;

β ₇ = 3.285.

The preoperative estimate of the likelihood of early residual pulmonary hypertension after pulmonary endarterectomy is then determined using the following formula:

$$P=\frac{e^Z}{1+e^Z}$$ , Where:

P - probability of early residual pulmonary hypertension after pulmonary endarterectomy.

z - calculated regression function.

e is the base of the natural logarithm (e=2.7183).

If the P value ≥ 0.409 in a patient before a planned pulmonary endarterectomy, a high probability of early residual pulmonary hypertension in the postoperative period is predicted; with P < 0.409, a low probability of early residual pulmonary hypertension in the postoperative period is predicted.

The sensitivity of the constructed model on the training set was 91.7%, specificity - 95.8%, diagnostic accuracy (percentage of correct classification) - 94.8%.

ROC analysis was used to assess the quality of the model built using logistic regression. The AUC (Area Under Curve) value was 0.847 (CI [0.761, 0.932], p <0.001).

As a condition for choosing the optimal separation threshold for differentiating residual pulmonary hypertension, the criterion of “maximum total sensitivity and specificity” was used. The final operating characteristics of the model at the cutoff point P = 0.409 were: sensitivity - 0.81, specificity - 0.86, diagnostic accuracy - 0.84.

Brief description of the drawings. Figure 1 shows the ROC curves of sensitivity and specificity of the model, where the X-axis indicates sensitivity and the Y-axis indicates specificity.

Implementation of the invention.

When preoperatively assessing the likelihood of early residual pulmonary hypertension after pulmonary endarterectomy, the following are taken into account: body mass index - measured in kg/m², blood group A (II) according to the AB0 system - presence/absence, the value of the international normalized ratio on admission - measured in units, expiratory reserve volume according to body plethysmography is measured in liters, minute respiratory volume according to body plethysmography is measured in l/min, left ventricular ejection fraction according to transthoracic echocardiography is measured as a percentage, bronchopulmonary resistance according to body plethysmography is measured in kPa*s. Based on the data obtained, a preoperative assessment of the likelihood of early residual pulmonary hypertension after pulmonary endarterectomy is carried out. Depending on the value of the probability indicator, patients are classified into a group with a high probability of having early residual pulmonary hypertension or into a group with a low probability.

Example 1

Patient P., 21 years old, was hospitalized at the National Medical Research Center named after. ak. E.N. Meshalkin" of the Ministry of Health of Russia to perform pulmonary endarterectomy with complaints of shortness of breath during moderate physical exertion; heartbeat.

Clinical diagnosis on admission: Chronic thromboembolic pulmonary hypertension. Severe tricuspid valve insufficiency. CHF stage IIA, FC III (NYHA).

table 2 Indicators taken into account in the calculation Index Meaning body mass index 20.3 blood type A (II) No (0) international normalized ratio on admission 1.44 preoperative expiratory reserve volume 2.2 minute breathing volume before surgery 16 preoperative left ventricular ejection fraction 58 bronchial resistance before surgery 0.44

Before the planned pulmonary endarterectomy, we will carry out calculations for patient P. using a model created on the basis of logistic regression. First we determine the value of the Z function:

Z= α+β ₁ X ₁ +β ₂ X ₂ +β ₃ X ₃ +β ₄ X ₄ +β ₅ X ₅ +β ₆ X ₆ +β ₇ X ₇ ,

Substituting the values into the formula, we get:

Z=-8.651) + (-0.126*20.3) + (-2.823*0) + (0.914*1.44) + (1.654*2.2) + (0.170*16) + (0.090*58) + (3.285*0.44) = 3.13156

Now let’s substitute the value of the function Z= 3.13156 into the formula:

$$P=\frac{e^Z}{1+e^Z}$$

$$P=\frac{e^Z}{1+e^Z}=\frac{e^{3.13156}}{1+e^{3.13156}}=\frac{22.91017}{1+22.91017}=\frac{22.91017}{23.91017}=0.95818$$

According to the model results, the P value = 0.95818 > 0.409, therefore, patient P. before the planned pulmonary endarterectomy has a high probability of early residual pulmonary hypertension in the postoperative period. The result of this clinical case, after a successful pulmonary endarterectomy, was a significant decrease in the mean pressure in the pulmonary artery, but the pressure remained above 25 mmHg. Art. during catheterization of the right heart, thus, patient P. has residual pulmonary hypertension after pulmonary endarterectomy.

Example 2

Patient G., 37 years old, was hospitalized at the National Medical Research Center named after. ak. E.N. Meshalkin" of the Ministry of Health of Russia for pulmonary endarterectomy with complaints of shortness of breath with minimal physical exertion, accompanied by a burning sensation in the chest without irradiation; heartbeat; periodic swelling in the face; swelling of the veins of the neck when lying down; increased fatigue; periodic dry cough or cough with scanty light sputum.

Clinical diagnosis on admission: Chronic thromboembolic pulmonary hypertension. Right atrium thrombus. Previous pulmonary embolism from 2017. Moderate tricuspid valve insufficiency. CHF IIB stage, FC III (NYHA).

Table 3 Indicators taken into account during diagnosis Index Meaning body mass index 24.6 blood type A (II) Yes (1) international normalized ratio on admission 1.12 preoperative expiratory reserve volume -0.43 minute breathing volume before surgery 15 preoperative left ventricular ejection fraction 78 bronchial resistance before surgery 0.59

Before the planned pulmonary endarterectomy, we will carry out calculations for patient G. using a model created on the basis of logistic regression. First we determine the value of the Z function:

Z= α+β ₁ X ₁ +β ₂ X ₂ +β ₃ X ₃ +β ₄ X ₄ +β ₅ X ₅ +β ₆ X ₆ +β ₇ X ₇ ,

Substituting the values into the formula, we get:

Z=-8.651+(-0.126*24.6)+(-2.823*1)+0.914*1.12+(1.654*(-0.43))+0.170*15+ 0.090*78+3.285*0, 59=-2.75299

Now let’s substitute the value of the function Z = -2.75299 into the formula:

$$P=\frac{e^Z}{1+e^Z}$$ $$P=\frac{e^Z}{1+e^Z}=\frac{e^{-2.75299}}{1+e^{-2.75299}}=\frac{0.0637358}{1+0.0637358}=\frac{0.0637358}{1.0637358}=0.0599$$

According to the model results, the P value = 0.0599 <0.409, therefore, patient G. before the planned pulmonary endarterectomy has a low probability of early residual pulmonary hypertension in the postoperative period. The result of this clinical case, after a successful pulmonary endarterectomy, was a complete recovery, since the average pressure in the pulmonary artery during catheterization of the right heart became less than 25 mm Hg.

Claims (23)

A method for preoperative assessment of the likelihood of early residual pulmonary hypertension after pulmonary endarterectomy, characterized by determining the patient’s body mass index, the presence or absence of the patient’s blood group A (II), using body plethysmography to measure the patient’s expiratory reserve volume, minute respiratory volume and bronchial resistance, determine the left ventricular ejection fraction using transthoracic echocardiography, while the likelihood of early residual pulmonary hypertension after pulmonary endarterectomy is determined by the formula: $$P=\frac{e^Z}{1+e^Z}$$ , where P is the probability of developing early residual pulmonary hypertension after pulmonary endarterectomy; e – base of natural logarithm, e=2.7183, z – regression function, which is calculated by the formula: Where - free term of the equation equal to -8.651; X ₁ - body mass index - measured in kg/m²; X ₂ - belonging to blood group A (II): if the patient has blood group A (II), then X ₂ is equal to 1, if not, then X ₂ is equal to 0; X ₃ - the value of the international normalized ratio upon admission; X ₄ - reserve expiratory volume according to body plethysmography; X ₅ - minute breathing volume according to body plethysmography; X ₆ - left ventricular ejection fraction according to transthoracic echocardiography; X ₇ - bronchopulmonary resistance according to body plethysmography; β ₁ , β ₂ , β ₃ , β ₄ , β ₅ , β ₆ , β ₇ - coefficients of the variables X ₁ , X ₂ , X ₃ , X ₄ , X ₅ , X ₆ , X ₇ , having the following values: β ₁ = -0.126; β ₂ = -2.823; β ₃ = 0.914; β ₄ = 1.654; β ₅ = 0.170; β ₆ = 0.090; β ₇ = 3.285, and with a P value of 0.409 or more, the probability of early residual pulmonary hypertension in the postoperative period is assessed as high, and with P less than 0.409, the probability of early residual pulmonary hypertension in the postoperative period is assessed as low.