Patients diagnosed with HCM in the first affiliated Hospital of Xinjiang Medical University from January 2016 to October 2019 were enrolled. The HCM patients underwent ECG, left ventriculography and coronary angiography. Among these patients, 32 without coronary artery stenosis were included in the HCM group (20 males and 12 females) . The average age of these patients was 44.69 ±10.63 years (ranged from 26 to 67 years). Twenty-eight patients, which included 18 males and 10 females, and age ranged from 30 to 72 years, with an average of (44.68 ±10.31) years, with negative ECG, left ventriculography and coronary angiography were selected as control.
Patients with HCM diagnosis were enrolled, and underwent examination by electrocardiogram, cardiac contrast ECG and coronary angiography at the same time. Patients with negative coronary angiography with a hypertrophic thickness of (19.00 ±3.45) mm were included. The degree of downward shift of ST segment is between 0.04mV and 0.3mV, and the degree of T wave flattening or inverted downward shift is between 0.1mV and 1.5mV. 28 in patients with negative ECG, cardiac contrast echocardiography and coronary angiography were selected as the control group. The myocardial thickness was about 0.00 ±0.00mm in cm, ST segment and 0 ±0.00mV during the T wave.
The inclusion criteria of HCM: All patients should meet the diagnostic criteria of HCM in adults according to the 2014 European College of Cardiology's guidelines for the diagnosis and Management of Hypertrophic Cardiomyopathy 9; the hypertrophic site involves interventricular septum with a thickness of ≥15mm, which is not only caused by abnormal cardiac load but also by myocardial hypertrophy of a class of cardiomyopathy. All patients have signed the informed consent form.
The exclusion criteria of HCM patients were as follows: patients with hypertrophic ventricular wall caused by hypertension, coronary heart disease, valvular disease, congenital heart disease and metabolic disease were excluded by examining the medical history, echocardiography, ECG and physical examination. Patients with obstructive HCM had left ventricular outflow tract pressure gradient of ≥ 30 mm Hg at rest. HCM patients who received surgical treatment and other ventricular wall hypertrophies caused by hypertension, coronary heart disease, valvular disease, congenital heart disease, Myocardial Bridge patient,metabolic disease and so on were excluded.
1.2 Instruments and methods.
1.2.1 ECG examination:
The subjects were placed in supine position, and a routine 12-lead ECG examination was conducted at rest. The paper speed was 25 mm/s, voltage 1 MV = 10 mm. The ECG was read by two clinically experienced attending physicians.
According to the recommendations of the updated global practice guidelines for remote health and arrhythmia monitoring during and after the HRS/EHRA/APHRS/LAHRS/ACC/AHA pandemic, the starting point of the QRS wave or the horizontal line at the beginning of the QRS wave (usually the PR segment) should be considered as the baseline, and the lowest depression amplitude should be selected for measurement.
The results were as follows:
If the ST segment moved downwards when compared to the baseline, and the duration was more than 0.12s, then the degree of ST depression was divided into different groups ST1, ST2 and ST3 according to different cut off values (0.1mV；0.2mV ；0.3mV).
(in which 0 <ST≤0.1mv is the ST1 group; 0.1mv <ST≤0.2mv is the ST2 group; and 0.2mv <ST≤0.3mv is the ST3 group)
1.2.2 Instruments and contrast agents.
The images were analyzed offline using Philips EPIQ7C ultrasonic instrument, with S5mur1 phased array probe and QLab software at a frequency of 3.5mur5.0MHz. Ultrasound contrast agent Sonowei (produced by Boleko, Italy) with SF6 gas of 59 mg, and freeze-dried powder 25 mg was used. Before its use, 5 ml normal saline (0.9%Nacl) was mixed with the agent, followed by shaking hard to form a milky liquid.
1.2.3 Contrast-enhanced ultrasound:
A synchronous ECG was connected to the established venous access. The patient was placed on left lying position, followed by adjusting the machine, optimizing the image, routinely measuring and evaluating the size and function of the heart, and then switching to LVO imaging mode (TIS 0.7 ~ MI 1.4). According to the imaging situation, an intravenous injection of contrast medium after well shaking, a 1mL extract was injected through the left elbow vein. Within 2 minutes of injection, 1 ml saline was used to flush, observe and acquire the image. The dynamic images included apical four-chamber view, apical two-chamber view, apical three-chamber view, left ventricular long-axis view, mitral valve, papillary muscle and apical horizontal view of the left ventricle for 5 consecutive cardiac cycles. After that, switch to MCE mode (TIS 0.8, flash MI 1.5), the 1mL extract was quickly injected through the left elbow vein, then rinsed with 1ml saline, and acquired the images. The flash key was pressed (8 frames, MI = 0.9), in which a high energy pulse was produced to destroy the myocardial contrast microbubbles, and observe the process of myocardial microbubbles filling again. Five consecutive cardiac cycles were recorded before "flash", and 10 consecutive cardiac cycles were recorded after "flash". The process was completed by two experienced doctors and a nurse, and all the retained images were saved and analyzed.
1.2.4 Ultrasonic image analysis.
The stored images were transferred to a QLAB workstation, started the analysis software, and placed the region of interest of size and shape (5 mm × 5 mm) in the centre of the hypertrophic myocardium, avoiding the hyperechoic area as far as possible (considering the abnormally high value of variant or compensatory hyperplastic vessels that affects the results of the analysis). Proofread the position of the interesting region frame by frame, delete the frame with excessive displacement, ensure that it is located in the hypertrophic part and dynamically track each region of interest in the whole image analysis, and select all images of 10 cardiac cycles after flickering to establish the time-intensity curve. Similar method was used in the control group to select the central region of the interventricular septum. Finally, the ultrasonic perfusion parameters including the peak intensity (PI), area under the curve (AUC), rising slope (RS), and time to peak (TTP) were analyzed. PI is the maximum value of the curve, which indicated the maximum volume of the blood and the area under the curve (AUC). This meant that the blood in the selected unit time showed positive correlation with the total blood volume. PI and AUC are related to blood volume. The RS represents the rising slope of the fitting curve, and the time to peak (TTP) represents the time it takes for the curve to reach the highest point.Measurement of electrocardiogram and ultrasonic perfusion parameters in hypertrophy group and control group (figure 1).
1.3 Statistical methods.
SPSS 19.0 software was used to analyze the data. The measurement data were expressed as means±standard deviation. The data in accordance with normality and homogeneity of variance were compared by t-test, and the data that was not in accordance with normality and homogeneity of variance were compared by rank sum-test. The counting data were compared by χ2 test, and comparison among the three groups was done by single-factor analysis of variance and LSD method was used for pairwise comparison. Pearson correlation analysis was used to analyze the correlation. The test standard α = 0.05 (P<0.05) was considered to be statistically significant. Bland-Altman plots were used to analyze the repeatability of ultrasound perfusion parameters measured twice by different observers. By observing the intra-group correlation coefficient (intraclass correlation coefficient, ICC), the ICC >0.75 represents good repeatability, the 0.4 <ICC <0.75 represents good repeatability, and the ICC <0.4 represents poor repeatability.