Study population
Patients who were diagnosed with nonobstructive hypertrophic cardiomyopathy at the First Affiliated Hospital of Xinjiang Medical University from October 2017 to July 2019 were selected as the case group. Of these, 19 were men, and nine were women ranging in age from 40 to 73, with an average age of 52.07±9.91 years. Healthy volunteers were selected as normal controls, including twenty men and eight women ranging in age from 37 to 72, with an average age of 51.13±10.38 years. All patients underwent coronary angiography, and echocardiography was performed within 1 week before coronary angiography.
Case group selection criteria
According to the 2014 European Society of Cardiology (ESC) diagnostic guidelines for hypertrophic cardiomyopathy.
(1) Echocardiography, cardiac magnetic resonance imaging or computed tomography imaging is used to confirm that the wall thickness of one or more segments of the left ventricular myocardium is ≥15 mm, which cannot be explained by myocardial hypertrophy caused by abnormal cardiac load alone.
(2) Patients with a wall thickness of 13~14 mm should undergo evaluation of their family history, noncardiac-related symptoms, electrocardiogram abnormalities, laboratory tests, and various cardiac imaging modalities, as well as comprehensive evaluation of whether hypertrophic cardiomyopathy is diagnosed.
(3) Cardiac imaging of a patient’s first-degree relatives with well-diagnosed hypertrophic cardiomyopathy with thickness ≥13 mm can be used to diagnose hypertrophic cardiomyopathy of a segment or segments of the left ventricular wall that cannot be clearly explained.
(4) All patients had normal coronary angiography.
(5) Informed consent was provided by all subjects.
Patients were divided into HS groups and NHS groups according to myocardial thickness
Myocardial thickness was measured by two-dimensional ultrasound based on the left ventricular 17-segment method. Myocardial thickness ≥13 mm was observed in the hypertrophic myocardial segment group (hypertrophic myocardial segment, HS). Myocardial thickness <13 mm is the nonhypertrophic myocardial segment group (nonhypertrophic myocardial segment, NHS).
Control Criteria
Healthy subjects were matched by sex and age to the nonobstructive HCM group (all control participants had no history of vascular disease, normal cardiac ultrasound and electrocardiogram, and no other organic diseases).
Exclusion criteria
(1) Patients with ventricular wall hypertrophy caused by hypertension, coronary heart disease, diabetes, congenital heart disease, metabolic disease, etc. after medical history, echocardiogram, electrocardiogram, and physical examination, and nonobstructive HCM patients who have undergone surgery.
(2) Those with high gas interference and poor image quality.
(3) Patients with obstructive hypertrophic cardiomyopathy were excluded. According to the left ventricular outflow tract pressure difference >30 mmHg at rest or under load, nonobstructive HCM patients were ultimately selected.
Inspection methods
Instruments and contrast agents
A Philips EPIQ 7C was used with S5-1 probes at a frequency of 3.5 MHz and a frame frequency of 55-90 frames/s. The contrast agent was made from Sonovir SonoVue (Boulaco, Italy; SF6 gas 59 mg, lyophilized powder 25 mg). The bottle was oscillated with 5 ml of 0.9% sterile sodium chloride injection for 20 seconds until the freeze-dried powder was completely dispersed and a homogeneous white emulsion was obtained. Avenous passage was established at the median vein of the elbow. Two milliliters of suspension was extracted for intravenous injection. Finally, the tube was flushed with 1 ml saline at the same rate [8-9].
Image acquisition
Myocardial echocardiography: The subject takes the left decubitus position, establishes venous access, connects to the synchronized electrocardiogram, adjusts the machine, optimizes the image, routinely measures heart size and evaluates heart function. Switch to the LVO imaging mode (TIS=0.7, MI=1.4), according to the imaging situation, intravenous bolus injection of contrast agent, observe and save the images, and the dynamic images include apical four-chamber view, apical two-chamber view, and apical three-chamber view, left ventricle long axis view, left ventricle short axis view of the mitral valve, papillary muscle, and apex of the heart to record 5 consecutive cardiac cycles. Switch to MCE mode (TIS=0.8, MI=1.5), save the observation image, and then press the Flash button (MI=0.95), (Note: Flash button function: use high MI to instantly crush microbubbles to clear myocardial microcirculation microbubbles), and then continue to retain the image for 10-15 cardiac cycles.
2D-STI: The subjects maintained a left lateral position with calm breathing, and synchronous recording of the electrocardiogram was performed by recording the apical left ventricular long axis, apical four-chamber and apical two-chamber section of the three cardiac cycle dynamic images. Images were then stored for offline analysis, as shown in Figure 1.
18F-FDG PET myocardial glucose metabolism imaging:Use Siemens Biography 6 PET/CT scanner. An intravenous injection of 4-6 mCi 18F-FDG (Beijing Atom Technology Co., Ltd.) was performed on an empty stomach (fasting for more than 12 hours), and PET/CT myocardial metabolism imaging was performed after 90 minutes of rest. The PET collection time was 10 min, and the CT collection parameters were 120 kV tube voltage, 11 mAs tube current, and 3 mm layer thickness.
Image analysis
Quantitative analysis of myocardial contrast
Using QLAB 10.8 analysis software to place the area of interest (ROI) in the left ventricular myocardium, the ROI position was fixed with correction tracking. The system fitted the time curve with the intensity of the myocardial acoustic signal in the sampling frame. Acoustic perfusion parameters included peak intensity (PI) and area under the curve (AUC). PI was the maximum value of the curve, representing the maximum volume of blood, and AUC was positively correlated with the total blood volume; PI and AUC were parameters related to blood volume. The elevation slope (rising slope, RS) represents the rising slope of the fitting curve; peak time (time to peak, TTP) indicates the time required for the curve to reach its highest point.
Standardized myocardial perfusion parameters
To eliminate the effect of myocardial thickness on myocardial perfusion in patients with nonobstructive HCM, myocardial perfusion parameters were standardized and calculated per unit area. The specific methods were as follows: the thickest segment myocardial perfusion parameters PI, AUC, RS, TTP divided by the corresponding thickest myocardial thickness (TMT)
Standardized peak intensity (Standardization peak intensity, s-PI) = PI/TMT.
Area under the standardized curve (Standardization area under curve, s-AUC) = AUC/TMT.
Standardized ascending slope (Standardization rising slope, s-RS) = RS/TMT.
Standardized peak time (Standardization time to Peak, s-TTP) = TTP/TMT.
Two measurements from the same person were tested for repeatability, and if the consistency was good, the average value was taken as the ultrasonic perfusion parameter value.
Quantitative analysis
In QLAB 10.8 analysis software, the cardiac motion quantitative analysis was entered into the CMQ interface. The long axis, apical four-chamber and apical two-chamber sections of the apical left ventricle were analyzed. The left ventricular lateral wall of the mitral annulus, the septum of the mitral annulus and the apex of the heart were manually located. The software automatically outlines the endocardial region and manually fine-tunes the area of interest; the work-strain-time curves of the left ventricle were then obtained. The overall longitudinal strain of the left ventricle (global longitudinal strain, GLS), overall circumferential strain (global circumferential strain, GCS), stroke output (stroke volume, SV), end-diastolic volume (EDV), and end-systolic volume (ESV) were obtained. GLS reflects the longitudinal contractile function of the myocardium, and GCS is mainly produced by the contraction of myocardial fibers in the middle loop.
Two nuclear medicine physicians with 5 years of work experience and above will jointly read the film, and the third nuclear medicine physician (with more than 10 years of work experience) will make a judgment if they disagree. The left ventricular myocardium is divided into 17 segments, and the myocardial metabolism image is scored by the semi-quantitative 5-point method: one point represents radioactive concentration, zero point represents normal radioactivity distribution, and one generation.It means that the radioactivity is slightly reduced. A score of 2 represents a significant reduction in radioactivity, and a radioactive defect in the third generation; the score of 17 segments is added to obtain the total metabolic score.
Statistical analysis
SPSS 23.0 statistical software was used to analyze and collate the data, and count data are described by the number of examples. Shapiro-Wilk normality test, according to the normal distribution, the measurement data are described by the mean ± standard deviation (x̄ ± s), and the comparison between the two groups is analyzed by independent sample t test. The continuous data of normal distribution were analyzed by variance F test, and the comparison between two groups was analyzed by LSD-t method. The nonparametric rank and test analysis was used for intergroup comparisons of continuous data that did not conform to a normal distribution. Correlation analysis was performed with Spearman correlation analysis. The difference was statistically significant when the test level α = 0.05 (P<0.05).