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Research Article

Computed tomography myocardial perfusion imaging of patients with left ventricular hypertrophy in hypertension: A retrospective study

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Article: 2159426 | Received 27 Jul 2022, Accepted 12 Dec 2022, Published online: 03 Jan 2023

ABSTRACT

Objective

Left ventricular hypertrophy (LVH) is a strong predictor of adverse cardiovascular outcomes including heart failure. This study evaluated characteristics and the influencing factors of computed tomography myocardial perfusion imaging (CT-MPI) of patients with LVH in hypertension.

Methods

A total of 65 patients with stable chest pain and confirmed coronary stenosis <50% by coronary computed tomography angiography (cCTA) from September 2019 to February 2021 were recruited. According to the results of echocardiography, patients were divided into the LVH group (n = 33) and control group (patients without LVH, n = 32). The general data of all study subjects were collected, and the body mass index (BMI) and body surface area (BSA) were calculated. Myocardial blood flow (MBF), myocardial blood volume (MBV), and echocardiographic parameters were recorded. Spearman correlation analyses were conducted to analyze the relationship between MBF, MBV, and echocardiographic parameters.

Results

The LVH group had significantly higher left ventricular end diastolic distance (LVEDd), septal wall thickness diastole (SWTd), and post wall thickness diastole (PWTd) than the control group, resulting in higher left ventricular mass index (LVMI) (P < .05). The LVH group showed significantly lower MBF than the control group (P < .05), but there was no significant difference in MBV between two groups (P > .05). Spearman correlation analysis demonstrated that MBF was negatively correlated with SWTd and LVMI (P < .05).

Conclusions

CT-MPI, as a new noninvasive modality to evaluate myocardial perfusion in hypertensive patients, revealed that MBF is reduced in patients with LVH, while MBV remains unchanged. In hypertensive patients, decreased MBF is significantly correlated with increased LVMI.

Introduction

Hypertension is one of the main risk factors for cardiovascular and cerebrovascular diseases (Citation1). Hypertension can cause structural and functional changes in the heart, brain, kidney, and blood vessels, ultimately leading to cardiovascular and cerebrovascular events (Citation2). The prevalence of hypertension is increasing year by year worldwide. It is estimated that 15.6 billion hypertensive patients will reach worldwide in 2025 (Citation3). Both cardiac afterload and preload can be aggravated in hypertensive patients, resulting in increased cardiomyocyte size and myocardial volume, changes in myocardial collagen matrix composition, and causing left ventricular hypertrophy (LVH) (Citation4,Citation5). Hypertensive patients with LVH have increased myocardial oxygen consumption. In addition, coronary artery dilatation cannot meet the needs of thickened myocardium for increased blood flow, resulting in decreased coronary flow reserve (CFR), myocardial ischemia, and myocardial blood flow (MBF) (Citation6,Citation7). Previous studies have confirmed that MBF is significantly reduced in hypertensive patients with LVH using positron emission tomography (PET), single-photon emission computed tomography (SPECT), myocardial contrast echocardiography, and magnetic resonance imaging (MRI) imaging techniques (Citation8–10). With the advancement of computed tomography (CT) technology, dynamic stress CT myocardial perfusion imaging (CT-MPI), as a newly developed CT imaging technology, integrates coronary computed tomography angiography (cCTA) and myocardial blood perfusion scanning. CT-MPI examination can provide morphological information such as coronary artery stenosis and functionally assess myocardial blood perfusion, offering a new way to determine the degree of coronary artery stenosis and quantify myocardial blood perfusion (Citation11–14). However, in non-obstructive coronary artery stenosis hypertensive patients, few studies utilized the CT-MPI technique to assess the effect of hypertension with LVH on myocardial blood perfusion. Therefore, the main purpose of this study was to determine the characteristics and the influencing factors of CT-MPI of patients with LVH in hypertension.

Materials and methods

General information

A total of 65 patients with stable chest pain through clinical assessment and confirmed coronary stenosis <50% by cCTA from September 2019 to February 2021 were recruited in this retrospective study. All patients underwent echocardiography. General information of the patients, such as the age, sex, systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), body mass index (BMI), and body surface area (BSA), diabetes, low-density lipoprotein cholesterol (LDL-C), smoking history were collected. Echocardiographic parameters such as diastolic distance (LVEDd), septal wall thickness diastole (SWTd), and post wall thickness diastole (PWTd) were also recorded to calculate the left ventricular mass (LVM). The LVM was calculated using the Devereux formula (Citation15): LVM = 0.8 × 1.04 [(LVEDd + SWTd + PWTd)3 − (LVEDd)3+ 0.6]. The left ventricular mass index (LVMI) was calculated by the formula (Citation15): LVM/BSA. According to the LVMI values, patients were divided into LVH group (Male: LVMI >108 g/m2, Female: LVMI >99 g/m2) and control group (Male: LVMI ≤108 g/m2, Female: LVMI ≤99 g/m2). The study was approved by the Daqing Oilfield General Hospital, China. Informed consent was obtained from all patients.

Inclusion criteria

(Citation1) According to the Guideline-driven management of hypertension (Citation16), hypertension was defined as patients with SBP ≥140 mmHg or DBP ≥90 mmHg (Citation2); Patients had stable chest pain and is highly suspicious of angina (Citation3); Patients with <50% epicardial coronary stenosis confirmed by cCTA (Citation4); Patients underwent CT-MPI scan successfully when cCTA was performed.

Exclusion criteria

(Citation1) Patients with epicardial coronary artery obstructive stenosis (coronary artery stenosis ≥50%) confirmed by cCTA (Citation2); Patients after coronary artery stenting (Citation3); Patients after coronary artery bypass grafting (Citation4); Severe arrhythmia (Citation5); Pregnancy status (Citation6); Other significant cardiac structural abnormalities caused by non-hypertension (Citation7); Secondary hypertension (Citation8); Thyroid disease (Citation9); Patients with hemodynamic instability (Citation10); Patients who are allergic to iodinated contrast agent or adenine (Citation11); Patients with renal insufficiency.

Dynamic stress CT-MPI

All patients were examined by third-generation dual-source CT (SOMATOM Force; Siemens Healthcare, Forchheim, Germany). Scanning parameter settings: scanning gantry rotation time, 0.28 s; Tube voltage, 80KV ×2; Tube current, using automated modulation technology. Scanning range: 1 cm below the level of the tracheal augmentation to 1 cm below the diaphragmatic surface of the heart. After the infusion pump injected adenosine into the left antecubital vein at a constant rate of 140 μg/kg/min for 3 min, a double-barrel high-pressure syringe (MEDRAD® Stellant CT Injection System, USA) injected 50 ml of enhancer (Ultravist 370 mg l/mL, Bayer HealthCare) into the right antecubital vein at a rate of 5.2 ml/s, and an additional 70 ml of normal saline at an equal flow rate. The scan was started simultaneously as enhancer injection, and a dynamic shuttle mode was adopted with a scan time of 37 s. The acquisition window was set at 250 ms after the R wave. At the end of the scan, adenosine injection was immediately stopped.

The CT-MPI reconstructed slice thickness was 1 mm, the interslice distance was 1 mm, and the convolution kernel was Qr36. The data were reconstructed and analyzed at a post-processing workstation (Volume Perfusion CT Body, Syngo MMWP workstation, Siemens Healthcare). Motion correction was performed before data analysis. Myocardial segmentation was based on the 17 segments cardiac segmentation model by the American Heart Association (AHA). The analyzed sections were positioned in four sections of the left ventricular short-axis: basal, middle, apical, and apical caps. Each section of each short-axis section was manually delineated as a region of interest (ROI), and the ROI was delineated at least 1 mm from the epicardial and epicardial membranes. The mean MBF for each segment is automatically generated by the software, along with the myocardial blood volume (MBV). The mean value was measured three times for each segment, and the measurements were completed by a senior cardiovascular radiologist. The mean MBF or MBV value of 17 segments of the myocardium was defined as MBF or MBV in each case. Two more independent observers were included in this study to control the quality of cCTA, CT-MPI, and echocardiographic parameters.

Statistical analysis

Statistical Product and Service Solutions (SPSS) statistics package (version 26.0; IBM, Chicago, IL, USA) was used for all statistical analyses. Categorical variables were described as the number of cases (percentage), and a chi-square test was used for comparison. All continuous variables’ data adhering to the normal distribution were revealed as the mean ± standard deviation (SD). Non-normally distributed variables are described by quartile M (P25, P75). Statistical differences between the two independent samples were assessed by t-test for continuous variables adhering to the normal distribution. Mann-Whitney U test was performed for non-normally distributed variables. The correlation analysis was assessed by Spearman correlation analysis. P < .05 was considered statistically significant.

Results

General clinical data

An overall of 65 patients consisted in this study, consisting of 33 cases in the LVH group and 32 cases in the control group. The general clinical information of the patients was provided in . There was no statistical difference in age, sex, BMI, BSA, SBP, DBP, and HR between the two groups (P > .05). However, there was a significance in diabetes, LDL-C, and smoking history between two groups (P < .05).

Table 1. Comparison of general clinical data between the two groups.

Echocardiographic and CT-MPI parameters

LVEDd in the LVM group and control group were 47.94 ± 4.06 and 45.19 ± 3.89 mm, SWTd were 12.48 ± 1.35 and 10.72 ± 1.49 mm, PWTd were 10.79 ± 1.32 and 9.28 ± 1.17 mm, and LVMI were 199.67 ± 12.07 and 85.69 ± 8.84 g/m2, respectively. The subjects such as LVEDd, SWTd, PWTd, and LVMI in the LVH group were significantly higher than those in the control group (P < .05) ().

Table 2. Comparison of echocardiographic parameters between the two groups (mean ± SD).

MBF in the LVM group and control group were 114 (92, 129) and 137 (117, 152) ml/100 ml/min and MBV were 13 (Citation10,Citation13) and 11 (Citation10,Citation14) ml/100 ml. MBF was significantly decreased in the LVH control group, and the difference had statistical significance (P < .05). MBV had no significant statistical difference between the two groups (P > .05) ().

Table 3. Comparison of CT-MPI parameters between the two groups (M (P25, P75)).

Correlation analysis of MBF, MBV, and echocardiographic parameters

The correlation analysis information of the research is displayed in . By drawing a scatter diagram, a monotonic relationship between the SWTd, PWTd, LVMI, and MBF is visually judged, respectively (). Spearman correlation analysis revealed that SWTd, PWTd, and LVMI in the LVH group were negatively correlated with MBF (rs = −0.839, P < .001; rs = −0.810, P < .001; rs = −0.972, P < .001). However, the correlation between LVEDd and MBF was not statistically significant (rs = −0.234, P = .061). The results of Spearman analysis suggested no correlation between MBV and echocardiographic parameters (P > .05).

Figure 1. Scatter diagram of SWTd and MBF.

Figure 1. Scatter diagram of SWTd and MBF.

Figure 2. Scatter diagram of PWTd and MBF.

Figure 2. Scatter diagram of PWTd and MBF.

Figure 3. Scatter diagram of LVMI and MBF.

Figure 3. Scatter diagram of LVMI and MBF.

Table 4. Correlation analysis of MBF, MBV, and echocardiographic parameters.

Discussion

LVH is defined as an absolute increase in LVM that can occur with or independently of dilatation. The upper limit of the normal reference range of LVMI in Chinese adults was calculated based on the normal range of echocardiographic examination in Chinese adults (Citation17), using BSA correction, and found that hypertensive LVH in Chinese adults is LVMI >108 g/m2 in men or >99 g/m2 in women. The commonly used diagnostic methods for LVH are electrocardiogram, magnetic resonance imaging (MRI), and echocardiography (Citation18,Citation19). Echocardiography is the most widely used test to screen and assess cardiac remodeling, especially in the diagnosis of severe hypertrophy due to its high sensitivity, high reproducibility, and high consistency with autopsy results (Citation20). There are various formulas for the echocardiographic assessment of LVM, and the cube method based on M-mode ultrasound is commonly used (Citation21), that is, LVM = 0.8 × l. 04 ((LVEDd+SWTd+PWTd)3-LVEDd)3 + 0.6. LVMI can be corrected using BSA or height. In this study, LVH was diagnosed using echocardiography. It was found that LVEDd, SWTd, and PWTd are significantly higher in patients with LVH than in the control group, resulting in a significant increase in LVMI. In clinical practice, attention should be paid to cardiac chamber diameter and wall thickness in hypertensive patients to identify the LVH population in hypertensive patients accurately.

CT-MPI is a continuous scanning with contrast agent injection in dynamic shuttle mode after the heart is fully loaded with drugs. The data are reconstructed and imported into a special workstation. The ascending aorta is selected as the input artery to obtain the time density curve (TDC) in the scanning slice. The change of density is the change of CT value, which reflects the change of enhancer concentration. CT perfusion imaging reflects changes in time-enhancer tissue concentration. The evolution of tissue concentration of enhancers is linear with blood perfusion, so CT-MPI truly, reliably, and directly reflects myocardial tissue hemodynamic parameters (Citation22,Citation23). MBF and MBV were calculated automatically by mathematical model software. The MBF represents the blood flow through a specific myocardial tissue per unit time, representing the flow of myocardial capillaries derived from the TDC slope (Citation24). MBV represents the total amount of blood volume within a specific myocardium and is derived from the integral of the area under the TDC (Citation25).

At present, PET has been widely used in clinical practice as the gold standard for evaluating myocardial perfusion (Citation26). To compare the agreement between CT-MPI and PET in evaluating myocardial blood perfusion, several studies have investigated the relationship between CT-MPI-calculated MBF and PET-calculated MBF, confirming a good correlation between the two imaging modalities (Citation27,Citation28). In this study, the functional assessment of myocardial blood perfusion by CT-MPI was used to investigate the characteristics of myocardial blood perfusion in hypertensive patients with LVH after adequate loading of the heart with glandular almond. As an endothelium-independent vasodilator, Adenosine dilates coronary arteries by binding to A2 receptors in coronary smooth muscle cells (Citation29). Adenosine is conducted to assess myocardial blood perfusion by dilating the anterior and small arteries responsible for coronary resistance (Citation30).

In this study, ml/100 ml/min was used as the unit of measurement of MBF, reflecting the blood volume passed per unit of myocardial volume per unit of time. MBV is defined as the blood volume within the myocardium and reflects the volume of microvessels filled with blood (Citation31). Rodriguez-Porcel et al. (Citation32) studied the blood perfusion characteristics of seven porcine models of renal artery hypertension using micro-CT. The results found that the myocardial vascular density of the hypertensive porcine model is increased compared with the normotensive control group, but the MBV is significantly reduced after adenosine loading. However, MBF showed no significant change after adenosine loading compared with the resting state. Our study demonstrated no significant differences in MBV between the LVH group and the control group, but MBF is significantly lower in the LVH group than in the control group.

In hypertensive patients with LVH, myocardial ischemia is more pronounced (Citation33). Direct quantification of myocardial blood perfusion may explain the relationship between hypertension-induced myocardial ischemia and major adverse cardiovascular events (MACE). Van Nierop et al. (Citation34) explored the difference of myocardial blood perfusion between hypertensive mice with LVH and normal mice using the MRI myocardial blood perfusion technique. The results indicated that myocardial perfusion in LVH mice is significantly lower than that in the control group, and decreased blood perfusion is significantly correlated with increased LVM. Laine et al. (Citation35) also found that MBF is significantly lower in hypertensive patients with LVH than in non-LVH patients and normotensive controls using PET myocardial perfusion imaging. However, some studies have yielded conflicting results. Kato et al. (Citation9) reported that resting MBF is significantly higher in hypertensive patients with LVH than in normotensive controls using MRI phase contrast. At the same time, MBF is not different between the two groups after adenosine triphosphate induced cardiac stress. The difference may be due to the different MBF units. In this study, using the CT-MPI technique, we found that there is a significant negative correlation between LVMI and MBF.

This study has the following limitations (Citation1): The presence or absence of alcohol history, family history of coronary heart disease, and receiving antihypertensive drugs were not investigated (Citation2); Only MBF and MBV were analyzed for myocardial blood perfusion, and parameters such as mean transit time and time to peak were not analyzed (Citation3); the radiation dose was not counted (Citation4); The number of cases in the LVH group is small, and the changes of CT perfusion imaging in hypertensive myocardial hypertrophy need to be further studied.

To sum up, CT-MPI can be used as a new method to assess myocardial blood perfusion in hypertensive patients with LVH. MBF is reduced in non-obstructive coronary artery stenosis hypertensive patients with LVH, while MBV does not change significantly. The reduction of MBF is negatively correlated with LVEDd, SWTd, PWTd, and LVMI.

Abbreviations

CT-MPI: computed tomography myocardial perfusion imaging; cCTA: coronary computed tomography angiography; LVH: left ventricular hypertrophy; BMI: body mass index; BSA: body surface area; MBF: Myocardial blood flow; MBV: myocardial blood volume; LVEDd: left ventricular end diastolic distance; SWTd: septal wall thickness diastole; PWTd: post wall thickness diastole; LVMI: left ventricular mass index; CFR: coronary flow reserve; PET: positron emission tomography; SPECT: single-photon emission computed tomography; MRI: magnetic resonance imaging; CT: computed tomography; CT-MPI: computed tomography myocardial perfusion imaging; SBP: systolic blood pressure; DBP: diastolic blood pressure; HR: heart rate; BMI: body mass index; BSA: body surface area; LDL-C: low-density lipoprotein cholesterol; AHA: American Heart Association; ROI: region of interest; MBV: myocardial blood volume; TDC: time density curve; MACE: major adverse cardiovascular events.

Declarations

Ethics approval and consent to participate

The study was approved by the Daqing Oilfield General Hospital. Informed consent was obtained from all participants.

Availability of data and material

All data generated or analyzed during this study are included in this. Further enquiries can be directed to the corresponding author.

Author contributions

XW and FY are responsible for the guarantor of integrity of the entire study, study concepts & design, definition of intellectual content, literature research, clinical studies, experimental studies, data acquisition & analysis, statistical analysis, manuscript preparation & editing; LL Sun is responsible for the guarantor of integrity of the entire study, study concepts & design, experimental studies, statistical analysis, manuscript review. All authors read and approved the final manuscript

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The authors reported there is no funding associated with the work featured in this article.

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