Effect of quantitative parameters of contrast-enhanced ultrasound on the long-term prognosis of patients with chronic coronary syndrome
Highlight box
Key findings
• The quantitative parameters of contrast-enhanced ultrasound (CEUS) can be used as predictors of major adverse cardiovascular events (MACE) in patients with chronic coronary syndrome.
What is known and what is new?
• At present, there is a lack of research on the value of quantitative parameters of CEUS in predicting the long-term prognosis of patients with chronic coronary syndrome.
• Peak intensity of contrast agent at platform stage <4.54 dB and rising rate of microbubble reperfusion <0.275 s were found to be independent risk factors of MACE in patients with chronic coronary syndrome.
What is the implication, and what should change now?
• Quantitative parameters of CEUS can be used as predictors of MACE in patients with chronic coronary syndrome, and strengthening the management of such high-risk patients may be beneficial to reduce the incidence of MACE.
Introduction
In recent years, with the change of diet and living habits, the incidences of arterial hypertension, diabetes, and hyperlipidemia have increased year by year, the incidence of coronary artery disease (CAD) has subsequently increased year by year, which is one of the main risk factors for death in middle-aged and elderly people (1-4). Chronic coronary syndrome (CCS) refers to the absence of major adverse cardiovascular events (MACE) such as myocardial infarction on the basis of severe stenosis of the coronary arteries. When the myocardial loading is increased due to exercise, transient myocardial ischemia and hypoxia symptoms can occur, manifested as transient angina. In addition, patients with CCS can experience MACE such as myocardial infarction, malignant arrhythmia, heart failure, and cardiac arrest. MACE is a major contributor to death in patients with CCS (5). Therefore, it is important to identify patients at a high risk of MACE. Coronary angiography has high value in predicting prognosis of patients with CCS, but it is invasive and difficult to measure dynamically (6-8). Ultrasound examination is non-invasive. However, in the early stage of CCS, due to the compensatory effect of the myocardium, left ventricular ejection fraction (LVEF) may not be significantly reduced. Contrast-enhanced ultrasound (CEUS), which has emerged in recent years, can assess the severity of myocardial ischemia (9,10). Therefore, we speculated that the quantitative parameters of CEUS can better assess the long-term prognosis of patients with CCS. Due to the lack of relevant studies, we designed this study. We present this article in accordance with the STARD reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1267/rc).
Methods
General information
From January 2016 to December 2017, a total of 473 patients with CCS admitted to Yueyang People’s Hospital were continuously and retrospectively enrolled and followed up for five years. According to whether the patients developed MACE or not, the patients were divided into the MACE group (n=113) and the control group (n=360). The inclusion criteria were as follows: (I) CCS (coronary diameter stenosis degree >50%, no MACE such as myocardial infarction in the past three months, but with the increase of myocardial loading due to exercise, occurrence of transient myocardial ischemia and hypoxia symptoms manifested as transient angina); (II) age ≥18 years; (III) complete clinical data. The exclusion criteria were as follows: (I) malignant tumor; (II) combined with other heart diseases such as congenital heart disease; (III) functional insufficiency of important organs such as the liver and kidneys; (IV) loss to follow-up. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). This retrospective clinical study was approved by the Yueyang People’s Hospital Ethics Committee (No. 20220072), and individual consent for this retrospective analysis was waived. The flowchart of the inclusion process is shown in Figure 1.
Inspection method
The ultrasounds were performed using a Philips IE33 Elite ultrasound diagnostic instrument (Philips Healthcare, Andover, MA, USA), with a X5-1 matrix probe (1.0–5.0 MHz); the contrast agent used was sulfur hexafluoride microbubbles (Brocoo Company, Italy, 59 mg). The real-time myocardial ultrasound imaging model was equipped. The second harmonic and pulse coding phase reversal harmonic imaging technology were used. The mechanical index was 0.08. We measured peak intensity of contrast agent at platform stage (reflecting myocardial blood volume) and rising rate of microbubble reperfusion (reflecting the average myocardial blood flow velocity). At the same time, routine ultrasound was performed to measure the LVEF. No intolerance nor allergic reactions occurred during the study period.
Data collection
(I) General information: age, gender, body mass index, arterial hypertension, diabetes, hyperlipidemia and medications taken; (II) ultrasound-related parameters: peak intensity of contrast agent at platform stage, rising rate of microbubble reperfusion, LVEF; (III) biochemical indexes: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high sensitivity c reactive protein; (IV) coronary artery stenosis: the number of coronary artery stenosis and the average degree of coronary stenosis.
Statistical analysis
The software SPSS 26.0 (IBM Corp., Armonk, NY, USA) was used to complete the data analysis, and a two-tailed P<0.05 indicated that the difference was statistically significant. The measurement data of the two groups were expressed by mean ± standard deviation, and the independent sample t-test was used to analyze the differences in the measurement data between the two groups. The counting data of the two groups were expressed by n (%), and the Chi-squared test was used to analyze the difference in the counting data between the two groups. The receiver operating characteristic (ROC) curve was used to analyze the value of ultrasound related parameters in predicting the occurrence of MACE in patients with CCS. Multivariate logistics regression analysis was used to explore the risk factors of MACE in patients with CCS.
Results
Comparison of clinical features of the two groups
There were statistical differences in the peak intensity of contrast agent at platform stage, rising rate of microbubble reperfusion, the LVEF, the number of coronary artery stenosis, and the average degree of coronary stenosis between the two groups (P<0.05) (Table 1).
Table 1
Variable | MACE group (n=113) | Control group (n=360) | t/χ2 value | P value |
---|---|---|---|---|
Age (years), mean ± SD | 61.50±11.77 | 61.49±12.04 | 0.005 | 0.996 |
Gender, n (%) | 0.247 | 0.619 | ||
Male | 72 (63.72) | 220 (61.11) | ||
Female | 41 (36.28) | 140 (38.89) | ||
Body mass index (kg/m2), mean ± SD | 26.36±3.25 | 26.27±3.03 | 0.281 | 0.779 |
Arterial hypertension, n (%) | 82 (72.57) | 250 (69.44) | 0.401 | 0.527 |
Diabetes, n (%) | 45 (39.82) | 122 (33.89) | 1.326 | 0.250 |
Hyperlipidemia, n (%) | 100 (88.50) | 300 (83.33) | 1.756 | 0.185 |
Antihypertensive drugs, n (%) | 82 (72.57) | 250 (69.44) | 0.401 | 0.527 |
Hypoglycemic drugs, n (%) | 45 (39.82) | 122 (33.89) | 1.326 | 0.250 |
Lipid lowering drugs, n (%) | 100 (88.50) | 300 (83.33) | 1.756 | 0.185 |
Aspirin, n (%) | 108 (95.58) | 330 (91.67) | 1.917 | 0.166 |
Peak intensity of contrast agent at platform stage (dB), mean ± SD | 4.04±0.50 | 5.04±0.71 | 13.959 | <0.001 |
Rising rate of microbubble reperfusion (s), mean ± SD | 0.24±0.03 | 0.29±0.04 | 12.275 | <0.001 |
Left ventricular ejection fraction (%), mean ± SD | 49.69±6.17 | 52.59±6.41 | 4.236 | <0.001 |
NT-proBNP (pg/mL), mean ± SD | 413.65±166.51 | 387.93±190.66 | 1.288 | 0.198 |
High sensitivity C reactive protein (mg/L), mean ± SD | 3.04±0.67 | 2.98±0.62 | 0.880 | 0.379 |
Number of coronary artery stenosis, n (%) | 21.982 | <0.001 | ||
Single | 39 (34.51) | 215 (59.72) | ||
Multiple | 74 (65.49) | 145 (40.28) | ||
Average degree of coronary stenosis, mean ± SD | 81.19±10.18 | 72.18±10.60 | 7.956 | <0.001 |
MACE, major adverse cardiovascular events; SD, standard error; NT-proBNP, N-terminal pro-B-type natriuretic peptide.
The value of average degree of coronary stenosis in predicting MACE in patients with CCS
The average degree of coronary stenosis was shown to be valuable in predicting MACE in patients with CCS, and the area under the curve (AUC) was 0.693 [95% confidence interval (CI): 0.636–0.750, P<0.001], the optimal diagnostic cut-off was 77.50%, and the sensitivity and specificity were 0.681 and 0.603, respectively (Figure 2).
The value of peak intensity of contrast agent at platform stage, rising rate of microbubble reperfusion, and LVEF in predicting MACE in patients with CCS
The peak intensity of contrast agent at platform stage, rising rate of microbubble reperfusion, and LVEF were found to be valuable in predicting the absence of MACE in patients with CCS. Among them, the peak intensity of contrast agent at platform stage had the highest predictive value, and the AUC was 0.860 (95% CI: 0.827–0.894, P<0.001) (Figure 3 and Table 2).
Table 2
Variables | Area (95% CI) | Standard error | P value | Optimal diagnostic threshold | Sensitiveness | Specificity |
---|---|---|---|---|---|---|
Peak intensity of contrast agent at platform stage (dB) | 0.860 (0.827–0.894) | 0.017 | <0.001 | 4.54 dB | 0.708 | 0.832 |
Rising rate of microbubble reperfusion (s) | 0.815 (0.774–0.855) | 0.021 | <0.001 | 0.275 s | 0.614 | 0.805 |
Left ventricular ejection fraction (%) | 0.626 (0.567–0.684) | 0.030 | <0.001 | 49.50% | 0.644 | 0.531 |
MACE, major adverse cardiovascular events; CI, confidence interval.
Risk factor of MACE in patients with CCS
Multivariate logistics regression analysis showed that the peak intensity of contrast agent at platform stage <4.54 dB and rising rate of microbubble reperfusion <0.275 s were independent risk factors of MACE in patients with CCS. The relative risks were 12.238 (95% CI: 6.632–22.585) and 5.724 (95% CI: 3.149–10.405), respectively (Table 3).
Table 3
Variables | B value | Standard error | Wald value | P value | Relative risk (95% CI) |
---|---|---|---|---|---|
Peak intensity of contrast agent at platform stage <4.54 dB | 2.505 | 0.313 | 64.193 | <0.001 | 12.238 (6.632–22.585) |
Rising rate of microbubble reperfusion <0.275 s | 1.745 | 0.305 | 32.743 | <0.001 | 5.724 (3.149–10.405) |
Left ventricular ejection fraction <49.5% | 0.736 | 0.284 | 6.733 | 0.009 | 2.087 (1.197–3.639) |
Multiple coronary artery stenosis | 1.054 | 0.288 | 13.439 | <0.001 | 2.870 (1.633–5.044) |
Average degree of coronary stenosis >81.50% | 1.155 | 0.286 | 16.314 | <0.001 | 3.174 (1.812–5.559) |
Constant | −9.222 | 1.041 | 78.513 | <0.001 | 0.000 |
MACE, major adverse cardiovascular events; CI, confidence interval.
Discussion
The basis of lesions in patients with CAD is coronary atherosclerosis, which leads to coronary stenosis, which in turn leads to insufficient blood supply to the myocardium. Long-term chronic myocardial ischemia can also lead to myocardial remodeling that progresses to MACE (11). In patients with CCS, there may be no significant change or only with a mild decrease in LVEF at early stage due to myocardial compensation (12-14). The present study also showed that LVEF was poor in predicting the MACE. However, in the early stages of CCS, patients exhibit changes in myocardial microvascular perfusion (15-17). Researchers have evaluated microvascular perfusion using CEUS (18,19), and this study explored the relationship between quantitative parameters of myocardial CEUS and the occurrence of MACE in patients with CCS. In the present study, the peak intensity of contrast agent at platform stage and rising rate of microbubble reperfusion were measured by myocardial CEUS. The peak intensity of contrast agent at platform stage represents myocardial blood volume; a rising rate of microbubble reperfusion reflects the average blood flow velocity of the myocardium. The decrease in the peak intensity of contrast agent at platform stage and rising rate of microbubble reperfusion indicate that myocardial hypoxia and ischemia are severe, and MACE is more likely to occur (18). CEUS has become a very important and promising development direction for ultrasound diagnosis (20,21). CEUS is the observation of coronary arteries, heart valves, and other conditions under ultrasound based on the distribution of contrast agents. CEUS is valuable in checking the tumors arterial stenosis and thrombosis.
In the present study, special ultrasound imaging techniques were used to observe the microvascular perfusion of myocardium, which could sensitively reflect the microperfusion of myocardium and provide a better way to identify CCS patients with high-risk of MACE.
The limitation of this study includes it retrospective nature and its failure to dynamically monitor the quantitative parameters of CEUS. Additionally, we failed to study more prognostic factors in this retrospective study.
Conclusions
Predicting the prognosis of different diseases is currently a hot topic and focus of research (22-25). Quantitative parameters of CEUS can be used as predictors of MACE in patients with CCS, and strengthening the management of such high-risk patients may be beneficial to reduce the incidence of MACE.
Acknowledgments
Funding: None.
Footnote
Reporting Checklist: The authors have completed the STARD reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1267/rc
Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1267/dss
Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1267/prf
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1267/coif). The authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). This retrospective clinical study was approved by the Yueyang People’s Hospital Ethics Committee (No. 20220072), and individual consent for this retrospective analysis was waived.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
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