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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_4048_Библиотеки_им_академика_М_И_Перельмана
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non-invasive diagnosis of coronary blood supply issues, specialists were able to
find a convenient and effective method. Transthoracic ultrasound of the coronary
bed at rest in patients during routine echocardiography in large groups of patients,
is a relatively "young" method for diagnosing coronary blood flow problems. It is
capable of evaluating a number of important parameters that allow to determine the
dysfunction of the main heart vessels with a high probability.
In 2000, Norwegian scientists studied 59 people using the flow
continuity formula. They drew attention to the fact that the rate of coronary blood
flow at rest differs from person to person. Using Doppler sonography, measuring
the artery diameter and peak and average velocities in the coronary arteries, the
authors of the article came to the conclusion that higher rates of coronary blood
flow at rest are determined when the vessel lumen is insufficient in relation to the
mass of the myocardium distal to this area, as is the case with diffuse lung diseases
or moderate coronary atherosclerosis [7].
In 2007, researchers from India published a paper describing their
results of transthoracic imaging of the left main coronary artery. They used
transesophageal ultrasound, with adequate visualization for 801 (55%) patients out
of 1,456 ones. Using Doppler sonography, the researchers evaluated the blood flow
velocity in the LMCA. Mosaic, turbulent flow or diastolic velocity above 1.5 m/s
was considered pathological. In total, there were 40 people with a diastolic blood
flow velocity of more than 1.5 m/s, of which 34 patients were diagnosed with
significant stenosis according to coronary angiography (sensitivity 85%).
Therefore, a team of scientists from India concluded that stenosis of the left main
coronary artery can be assessed using transthoracic echocardiography with an
acceptable degree of sensitivity and specificity. [8].
Two years later, Italian researchers have made transthoracic coronary artery
examination at rest using second harmonic Doppler sonography with enhanced
contrast to successfully diagnose anterior interventricular artery dysfunction in the
proximal, middle and distal regions. By the example of 53 patients with indications
for coronary angiography, they showed that in the areas of coronary arteries
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affected by atherosclerosis, according to coronary angiography, the blood flow
velocity determined using transthoracic ultrasound was significantly higher
compared to unaltered areas of the artery (143 +/-84 against 38 +/-20 cm/sec; P
<0.001). Sensitivity and specificity compared with coronary angiography were
86% and 95%, respectively. Therefore, Carlo Caiati et al. showed the possibility of
assessing blood flow in the anterior interventricular artery using transthoracic
ultrasound to detect coronary blood flow dysfunction.
[17]
Domestic cardiologists also described the possibility of diagnosing
stenosis of the heart arteries based on an increase in the blood flow velocity at rest
in the stenotic areas [1, 2].
Nevertheless, the effect of coronary blood flow parameters resulting from
transthoracic examination during echocardiographic screening is not sufficiently
studied. All previous works mainly involved groups of patients who had already
been referred for coronary angiography. These works only analyzed the
comparison of non-invasive and invasive data, that is, they only determined the
accuracy of coronary artery stenosis diagnosis in relation to coronary angiography
in patients with indications for coronary angiography. However, the role of altered
blood flow velocities as determined by routine echocardiography in a cohort of
“unselected patients” in the further prognosis of adverse cardiac events in these
patients is unclear. So far, only one retrospective paper by Japanese authors was
published on this topic. A one-center retrospective analysis of a patient cohort,
Morofuju T. et al. [92]. Based on a large sample of patients, the authors showed
that high blood flow velocities in the proximal portion of the left main coronary
artery and the anterior descending artery are associated with death and are an
independent predictor of adverse outcomes (myocardial infarction, heart failure,
sudden cardiac death in the period up to 6.3 years on average). However, the
retrospective study design does not allow for the reliable projection of the analysis
results to all patients, especially given the large percentage of lost patients included
in the above study.
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143
The world literature and the above paper still did not analyze the effect of
myocardial revascularization on further adverse events in groups of patients with
high coronary blood flow velocities visualized using transthoracic ultrasound. Thus,
transthoracic ultrasound of coronary arteries at rest is a promising non-invasive
method for diagnosing coronary artery disease and requires further study of the
effect of the resulting data on the patient prognosis and the role of myocardial
revascularization in patients with altered coronary blood flow according to
transthoracic ultrasound.
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Chapter 2. Materials and Methods
2.1 Clinical characteristics of patients
The prospective one-center study included 536 people (328 men – 61% and 208
women – 39%, mean age 60.4 ±11.5 years). The distribution of patients by sex and
age is shown in Fig. 2.1. Some of the data was used simultaneously for several
research tasks.
Figure 2.1 Distribution of patients by sex and age
2.2 Research methodology and methods
Different research stages had different inclusion and exclusion criteria described in
Chapters 3, 4, 5.
Survey and examination
All patients underwent a survey of complaints to identify the clinical
manifestations of coronary artery disease, arterial hypertension, diabetes mellitus,
and heart failure. We also collected anamnestic data on risk factors, past
cardiovascular events (myocardial infarction, acute coronary syndromes, previous
interventions). All patients underwent a standard cardiological examination,
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145
which, among other things, included measuring blood pressure, pulse rate, and
calculating body mass index. Body mass index was calculated using the formula –
body mass (kg)/height x height.
Echocardiography
Patients underwent echocardiography on Vivid 7 Dimension and Vivid E9, GE
ultrasound scanners using M4S and M5S sectorial phased transducers according to
the protocols recommended by the international echocardiographic associations
[74]. The following echocardiographic parameters were used in multivariate and
comparative analyzes: mass of the left ventricular myocardium, the mass index of
the left ventricular myocardium calculated by the "area-length" formula; left
ventricular ejection fraction calculated by the disk method in two orthogonal apical
projections.
Transthoracic ultrasound of the coronary arteries
The factory default "Coronary" tab was used to visualize the coronary arteries.
Blood flow of the coronary arteries was scanned using M4S, M5S conventional
transthoracic sector transducers. All patients underwent a routine search for the left
main coronary artery, proximal circumflex artery (CA) and left anterior descending
artery (LAD) in the parasternal position along the short axis at the level of the aorta
modified for visualization of the left coronary sinus – Figure 2.2. The middle
third of the LAD was searched in additional positions between the apical bicameral
and parasternal planes along the long axis, so as to maximally visualize the anterior
interventricular groove – the blood flow of the middle third of the LAD. Figure
2.3.
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Figure 2.2. A – the left main coronary artery, the left anterior descending artery,
the circumflex artery. B – proximal left anterior descending artery
Figure 2.3. Color Doppler sonography of the middle third of the anterior
descending artery.
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Figure 2.4. Measurement of coronary blood flow velocity.
Variability of results between studies and among different researchers.
To study the variability of coronary blood flow measurements between researches
and among different researchers, all data were re-evaluated (without providing data
on the initial evaluation results) in 80 consecutive patients. Re-measurements were
taken more than 30 days after the initial analysis. Variability of measurements
among different researchers was based on the analysis of the evaluation results by
two different independent experts.
Stress echocardiography
Patients underwent an exercise test on a horizontal bicycle ergometer with visual
analysis of impaired left ventricular wall contractility using e-Bike EL & BP, GE
equipment. The starting power was 50 W and increased by 25 W every 2 minutes
until reaching the standard endpoints [15]. ECG data and blood pressure were
constantly monitored during the test. Echocardiographic monitoring was
continuous from the start of the test until reaching the peak load for each person.
At the first stage of evaluating the results, during the test, left ventricular function
was evaluated according to the standard seventeen-segment model [129] right after
the study. Each segment was graded on a 4-point scale, with a contractility score
ranging from 1-4 (1 for normal contractility, 2 for hypokinesis, 3 for akinesis, and
4 for dyskinesis). The index of impaired regional contractility of the left ventricular
walls (index of wall motion abnormalities, IWMA) was calculated at rest and at the
peak load as the sum of points divided by the number of segments. The difference
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in IWMA (ΔIWMA) at rest and during exercise were analyzed. The criterion for a
positive test was induced ischemia, the emergence or aggravation of impaired left
ventricular contractility.
Coronary angiography
Patients, with their consent, underwent coronary angiography in accordance with
clinical indications subject to international recommendations [90]. In total, 245
patients underwent coronary angiography at 77±63 days after ultrasound of
coronary blood flow. Specialists in endovascular diagnostics were not aware of
the velocity parameters of the coronary arteries. The coronary angiography
technique was as follows: The radial or femoral arteries were cannulated according
to Seldinger, a standard 6fr catheter was delivered to the orifices of the coronary
arteries, followed by contrasting and imaging using standard technology in at least
five projections , if necessary, expanding the scope of the study to nine projections.
At the end, the instruments were removed, and the puncture site was tightly
bandaged. The results were described immediately after the study; subsequently,
all studies were "blind" submitted for re-evaluation by independent experts. The
stenosis degree was presented as a percentage. Stenosis was considered significant
when the left coronary artery lumen narrowed by 50%, in other arteries – by more
than 70%. In cases of borderline coronary lesions, when lumen stenosis was
estimated in the range of 50-70%, stress echocardiography data were taken into
account or fractional blood flow reserve (FFR) was calculated according to
Montalescot et al., 2013. LAD lesions were classified according to the stenosis
levels into the proximal, middle, and distal regions. The region downstream the
main artery bifurcation and upstream the departure of the first large septal branch
was considered to be proximal, followed by the middle segment until the LAD
angulation. The indications for revascularization were accepted by the medical
council in accordance with the European recommendations, taking into account all
the data of the patient examination.
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149
Evaluation of clinical outcomes per year
The results were summed up on the basis of patient surveys at a doctor, analysis of
medical records and outpatient records, or telephone interviews with patients or
their immediate family members. Of the clinical outcomes recorded during
follow-up, the following severe coronary events, death, nonfatal myocardial
infarction, acute pulmonary edema, acute coronary syndrome (ACS), and
myocardial revascularization were considered endpoints. All events were
confirmed by medical documents. Overall mortality was taken into account to
avoid misclassification of death causes [75]. Myocardial infarction was determined
according to the existing criteria described by [122]. Myocardial revascularization
involved percutaneous intervention (PCI) with coronary artery stenting and/or
coronary artery bypass grafting (CABG).
Statistics
Continuous variables were described by mean and standard deviations, with
categorical data expressed as percentages. ANOVA analysis was made for multiple
comparisons. Kaplan-Meier survival curves were used. Proportions were compared
using the Pearson's Chi-square test and Fisher's exact test. ROC analysis was used
to evaluate the predictive accuracy of severe coronary events. To identify
independent factors interrelated with the patient prognosis , we made a multivariate
Cox analysis. To evaluate the relationship between each candidate variable and the
outcome, we made same-type analyses using Cox proportional hazards. Cox's
analysis took into account the following categorical and continuous data: age, sex,
weight, arterial hypertension, diabetes mellitus, previously diagnosed coronary
artery disease, past myocardial infarction, previous PCI, attitude to smoking;
ejection fraction, diastolic volume and left ventricular end-diastolic volume index,
maximum blood flow velocity in the proximal part of any artery, and the ratio of
the maximum LAD blood flow velocity to the maximum Cx artery blood flow
velocity. All variables with p <0.10 through the one-parameter analysis were
considered as candidate variables for the multi-parameter analyzes. The study of
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variability in the parameters involved the Bland-Altman method. Variability is
presented as a variation coefficient. Statistical analysis involved the Statistica
package v.10.0 (Stat Soft Inc., Tulsa, Oklahoma, USA) and MedCalc v. 4.8.1
statistical software (MedCalc Software bvba, Ostend, Belgium). The research
complies with the Declaration of Helsinki, the research protocol was approved by
the ethics committee, and all subjects provided signed informed consent.
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