Abstract
Objective
Strain imaging by two-dimensional speckle tracking echocardiography can detect severe coronary artery disease (CAD). This study aims to assess the diagnostic accuracy of various strain parameters in patients with non-ST segment acute coronary syndrome to detect the angiographic severity of CAD and also to compare among them.
Methods
This hospital-based observational study was conducted on 178 patients with NSTEACS and preserved left ventricular ejection fraction who presented in emergency or outdoor from July 2021 to December 2022. We excluded patients with prior coronary revascularization, heart failure, arrhythmia, more than trivial valvular heart disease, or poor acoustic window. Global longitudinal strain (GLS), peak systolic strain (SS), post systolic index (PSI), and systolic strain rate (SR) were calculated by speckle tracking with automated function imaging. Coronary angiography was done in all patients, and the syntax score was calculated.
Results
The strain parameters showed a significant correlation with the syntax score. There was a statistically significant difference in strain parameters between patients with left main (LM) or triple vessel disease (TVD) and others. Receiver operating characteristic (ROC) curve analysis showed that GLS had a better diagnostic accuracy for detecting LM or TVD than other strain parameters. GLS with a cut-off value of −11.2% had a sensitivity of 85.7% and specificity of 53.5% for detecting LM or TVD.
Conclusion
Strain imaging can be a helpful bedside adjunct to conventional investigations for detecting severe CAD in patients with NSTEACS.
Keywords: Coronary artery disease, Diagnostic accuracy, Non-ST segment acute coronary syndrome, Strain imaging, Speckle tracking echocardiography
1. Introduction
Despite the decline in age-adjusted cardiovascular disease (CVD) mortality over the past three decades, coronary artery disease (CAD) remains the leading cause of death worldwide.1 Unlike ST-segment elevation myocardial infarction (STEMI), all patients with NSTEACS (non-ST segment elevation acute coronary syndrome) do not require an immediate invasive strategy. Although several risk scores have been developed for patients with NSTEACS, these are either time consuming or may underestimate the severity in those who have normal baseline investigations and conventional echocardiography parameters.2, 3, 4 So, a single bedside investigation which is fast, easy to do and correlate with the severity of CAD is the need of the hour to categorize these patients who have a large area of myocardium at jeopardy so that an early invasive strategy can be planned. Strain imaging with two-dimensional speckle tracking echocardiography (2D-STE), in this respect, is a momentous breakthrough that has been found to discover subclinical left ventricular systolic dysfunction in various types of heart disease.5, 6, 7, 8
The concept of strain imaging lies behind the fascinating microarchitectural pattern of the left ventricle (LV) which has three layers of myocardial strands that change orientation from oblique in the sub-epicardium to circumferential in the middle and longitudinal in the sub-endocardium.9 Ischemia causes dysfunction of the sub endocardial longitudinal fibres earlier than other layers as they are farthest from the coronaries.10 Conventional echocardiography cannot detect such subtle dysfunction where the left ventricular ejection fraction (LVEF) remains normal. Global longitudinal strain (GLS) can identify patients with subclinical LV systolic dysfunction and is related to the angiographic severity of CAD.11, 12, 13, 14 In addition to the severity of CAD, strain imaging with 2D STE can predict acute coronary occlusion in patients with NSTEACS.15
Myocardial deformation mechanics have attracted investigators to explore other strain parameters like peak systolic strain (SS), post systolic shortening (PSS), strain rate and territorial strain. PSS is delayed longitudinal fibber shortening even after the aortic valve closure. PSS is found both in ischemia as well as transmural necrosis.16 Strain rate (SR), the rate of myocardial deformation, can also detect subclinical LV systolic dysfunction.17 Territorial strain is the strain of the territory supplied by a coronary artery.
There are few studies with various strain parameters in patients with NSTEACS. This study aims to observe the diagnostic accuracy of various strain parameters to detect angiographic severity of CAD in patients with NSTEACS and comparison among them. We have not included territorial strain in our study which is one of the limitations of the study.
2. Materials and methods
2.1. Study population
It was a single-centre hospital-based cross-sectional observational study carried out in a tertiary care centre from July 2021 to December 2022. We evaluated 203 consecutive patients above the age of 18 years who presented with NSTEACS with LVEF >50% and no wall motion abnormality on echocardiography. All the patients who did not give informed written consent for participation in the study, had a history of myocardial infarction, percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG), had congestive heart failure (CHF), significant valvular heart disease, arrhythmia, poor acoustic window and who refused coronary angiography (CAG) were excluded. As such, 25 patients were excluded due to poor acoustic window, significant valvular disease, and prior intervention. So, the study included 178 patients who were explained the purpose and nature of the survey. The Institutional Ethics Committee approved the study, and all participants gave written informed consent. The evaluation comprised history taking, examination, ECG, laboratory investigations, transthoracic two-dimensional echocardiography, and CAG.
2.2. Echocardiography
A complete conventional echocardiography examination for all patients was performed using Phillips Epic 7C ultrasound machine. Traditional echocardiographic variables were assessed according to the standards of the American Society of Echocardiography.18 STE was assessed by recording dynamic 2D ultrasound images of three consecutive end-expiratory cardiac cycles using a high frame rate (60–100 frames/s) and harmonic imaging acquired in the apical four-chamber, two-chamber, and apical three-chamber view. Subsequently, STE software (QLAB 10; Philips Medical Systems) was used to measure the GLS, Peak systolic strain, and SR offline with automated tracking and manual correction wherever required. PSS was quantified as post systolic index (PSI).19,20 The software automatically calculated the SR at the point of maximum systolic strain.
2.3. Coronary angiography
CAG was performed in Phillips Azurion Clarity IQ. Angiograms were obtained for each coronary vessel in at least two orthogonal. Significant CAD was defined as a reduction in vessel diameter by ≥ 50% for the left main coronary artery and ≥70% for the left anterior descending, left circumflex, and right coronary artery.21 The patients who did not meet the criteria mentioned above had insignificant CAD. The patient who had significant CAD were further classified as single vessel disease (SVD), double vessel disease (DVD), triple vessel disease (TVD), and left main (LM) disease. They were clubbed into Group A [Insignificant CAD; SVD, DVD] and Group B [LM or TVD]. Syntax score was calculated for patients with significant CAD, and patients were categorized as low score (≤22), intermediate score (23–32), and high score (≥33).22
2.4. Statistical analysis
Data were entered in a Microsoft Excel spreadsheet, cleaned for errors, and analyzed using SPSS version 25. Continuous variables are presented as means ± standard deviations, and categorical variables as frequencies and their 95% confidence intervals (CI). The Shapiro–Wilk test was used to verify distribution normality. Quantitative variables were compared among groups with the student t-test when these followed a normal distribution and the Kruskal–Wallis/Mann–Whitney U test for other distribution patterns. A significance threshold of p = 0.05 was applied for all statistical tests. Receiver operating characteristic (ROC) curve analysis was done to determine the best cut-off value of global longitudinal strain, peak systolic strain post systolic index, and peak systolic strain rate (SR) to diagnose significant CAD on coronary angiography. Sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratios were calculated for the above strain parameters at optimal cut-off value. Pearson correlation coefficient was calculated for the correlation of strain parameters with the SYNTAX score. Data are represented using appropriate charts, tables, and graphs.
3. Results
3.1. Baseline characteristics and conventional echocardiographic findings of study population
There were 178 patients enrolled during the study period after excluding 25 (12.3%) patients based on exclusion criteria. The baseline characteristics of subjects are summarized in Table 1. Most of the population was male (71.35%) with hypertension as the most prevalent risk factor. Patients with USAP were more common than NSTEMI. Patients with LM, TVD and DVD comprised around 52% of cases. Table 2 delineates the conventional echocardiographic parameters in patients with NSTEACS. LVEF was, although slightly less in Group B, but it was not statistically significant (p = 0.06). All other parameters were also similar between two groups.
Table 1.
Baseline characteristics of the study population.
| Variable | Value | |
|---|---|---|
| Sample size (n) | 178 | |
| Age (years) | 57.85 ± 10.55 | |
| Gender | Male [n (%)] | 127 (71.35) |
| Female [n (%)] | 51 (28.65) | |
| Risk factors | Smoking [n (%)] | 28 (15.73) |
| Diabetes Mellitus [n (%)] | 69 (38.76) | |
| Hypertension [n (%)] | 77 (43.26) | |
| Family history of CAD [n (%)] | 09 (5.06) | |
| Type of NSTEACS | USAP [n (%)] | 118 (66.29) |
| NSTEMI [n (%)] | 60 (33.71) | |
| Routine investigations | Hemoglobin (g/dl) | 13.21 ± 1.5 |
| Serum creatinine (mg/dl) | 0.94 ± 0.18 | |
| HbA1c (%) | 7.04 ± 1.84 | |
| Total cholesterol (mg/dl) | 174.53 ± 128.02 | |
| Triglyceride (mg/dl) | 146.62 ± 73.20 | |
| HDL (mg/dl) | 39.11 ± 11.25 | |
| LDL (mg/dl) | 111.70 ± 41.99 | |
| Cardiac biomarkers | Troponin I (ng/ml) (n = 62) | 5.82 ± 4.32 |
| CK-MB (ng/ml) (n = 47) | 44.57 + 25.47 | |
| Myoglobin (ng/ml) (n = 41) | 56.16 ± 8.57 | |
| NT pro-BNP (pg/ml) (n = 108) | 1207.25 ± 1304.70 | |
| Coronary angiographic diagnosis | Insignificant CAD [n (%)] | 17 (9.55) |
| SVD [n (%)] | 67 (37.64) | |
| DVD [n (%)] | 48 (26.97) | |
| LM and/or TVD [n (%)] | 46 (25.84) | |
| Syntax Score | 12.94 ± 10.35 | |
Plus-minus values are mean ± standard deviation.
NSTEACS non-ST segment elevation acute coronary syndrome, CAD coronary artery disease, USAP unstable angina pectoris, NSTEMI non-ST segment myocardial infarction, HbA1C glycosylated hemoglobin, HDL high-density lipoprotein, LDL low-density lipoprotein, CK-MB creatine phosphokinase MB, NT pro-BNP N terminal prohormone brain natriuretic peptide, SVD single vessel disease, DVD double vessel disease, TVD triple vessel disease, LM left main.
Table 2.
Conventional echocardiographic parameters between Group A and Group B.
| Parameter | (Group A) [n = 132] | (Group B) [n = 46] | p-value |
|---|---|---|---|
| LVEF (%) | 58.83 ± 5.30 | 57.24 ± 4.25 | 0.06 |
| E (cm/s) | 75.02 ± 18.16 | 75.55 ± 16.95 | 0.862 |
| A (cm/s) | 68.08 ± 18.41 | 73.66 ± 20.17 | 0.086 |
| e’ (cm/s) | 7.63 ± 2.19 | 7.08 ± 2.23 | 0.146 |
| E/A | 1.31 ± 1.49 | 1.16 ± 0.63 | 0.509 |
| E/e’ | 10.44 ± 3.44 | 11.61 ± 4.08 | 0.060 |
Data are expressed as mean ± standard deviation.
LVEF left ventricular ejection fraction.
3.2. Strain parameters in study population
Table 3 shows that the strain parameters (GLS, SS, PSI and SR) are statistically significantly different between Group A and Group B (p < 0.0001). This suggests that patients with LM/TVD have significantly lower GLS, SS and SR values and higher PSI values than others. When the strain parameters were assessed in different subgroups (Supplement table 1), it was found that as the severity increases from insignificant CAD to multivessel CAD, the values of GLS, SS and SR decreases significantly whereas the value of PSI increases. This means that there is a strong negative association of GLS, SS and SR with severity of CAD and strong positive association of PSI with severity of CAD. Bulls eye plot of GLS along the spectrum of CAD is depicted in Fig. 1. On intragroup analysis, we observed similar findings except for strain rate (Supplement table 2). Similarly, on Pearson Correlation analysis, it was found that strain parameters have strong correlation with the Syntax Score (Supplement table 3) as shown in Fig. 2.
Table 3.
Strain parameters between Group A and Group B.
| Parameter | (Group A) [n = 132] | (Group B) [n = 46] | p-value |
|---|---|---|---|
| GLS | −17.40 ± 2.91 | −12.48 ± 2.78 | <0.0001 |
| SS | −17.81 ± 3.05 | −12.78 ± 2.82 | <0.0001 |
| PSI | 7.04 ± 6.84 | 18.45 ± 4.64 | <0.0001 |
| SR (1/s) | −0.98 ± 0.40 | −0.74 ± 0.10 | <0.0001 |
Data are expressed as mean ± standard deviation.
GLS global longitudinal strain, SS peak systolic strain, PSI post systolic index, SR systolic strain rate.
Fig. 1.
Bulls eye plot picture of GLS of (A) LM, (B) TVD, (C) DVD, (D) SVD and (E) Insignificant CAD.
Fig. 2.
Correlation of A) GLS with Syntax score, B) SS with Syntax score, C) PSI with Syntax Score, and D) SR with Syntax Score.
3.3. Receiver operating characteristic (ROC) curve analysis
ROC curves of GLS, SS, PSI, and SR were constructed for the study population to detect the presence of significant CAD (SVD + DVD + LM/TVD), DVD + LM/TVD, LM/TVD and syntax score ≥22 which are represented in Fig. 3. The detailed ROC analysis and comparison of GLS, PSS, PSI, and SR with cut-offs, area under curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) are presented in Table 4. Although, SR has better AUC (0.553) for the detection for significant CAD than others, it was not found to be statistically significant (p = 0.25). Similarly, the AUC was not significant for the detection of DVD + LM/TVD and Syntax Score≥22. Statistically significant AUC was found for GLS, SS and PSI for the detection of LM/TVD. Out of these, GLS had the maximum AUC (0.726). It was found that with a cut-off value of −11.2%, GLS had a sensitivity of 85.7% and specificity of 54% for the detection of LM/TVD.
Fig. 3.
ROC curves of GLS, SS, PSI, and SR for the detection of A) Significant CAD, B) DVD or more disease, C) LM or TVD, and D) Syntax score> 22.
Table 4.
Comparison of strain parameters through the spectrum of patients with significant CAD.
| Variable | Parameter | SVD + DVD + LM ± TVD [n = 161] | DVD + LM ± TVD [n = 94] | LM ± TVD [n = 49] | SYNTAX≥22 [n = 31] |
|---|---|---|---|---|---|
| GLS | Cut off | −17.9 | −11.2 | −11.2 | −10.6 |
| AUC | 0.542 (0.461–0.621) | 0.554 (0.448–0.657) | 0.726 (0.580–0.844) | 0.626 (0.435–0.792) | |
| Sensitivity (%) | 74.07 | 88.89 | 85.71 | 66.067 | |
| Specificity (%) | 44.76 | 29.31 | 53.57 | 63.64 | |
| PPV (%) | 40.80 | 43.80 | 58.10 | 42.90 | |
| NPV (%) | 77.00 | 81.00 | 83.30 | 82.40 | |
| PLR | 1.34 | 1.26 | 1.85 | 1.83 | |
| NLR | 0.58 | 0.39 | 0.27 | 0.52 | |
| p value AUC | 0.3633 | 0.3682 | 0.0022 | 0.2925 | |
| SS | Cut off | −18.5 | −11.4 | −11.4 | −10.7 |
| AUC | 0.536 (0.455–0.615) | 0.560 (0.454–0.662) | 0.723 (0.576–0.841) | 0.586 (0.396–0.759) | |
| Sensitivity (%) | 75.93 | 88.89 | 85.71 | 66.67 | |
| Specificity (%) | 40.95 | 29.31 | 53.57 | 63.64 | |
| PPV (%) | 39.80 | 43.80 | 58.10 | 42.90 | |
| NPV (%) | 76.80 | 81.00 | 83.30 | 82.40 | |
| PLR | 1.29 | 1.26 | 1.85 | 1.83 | |
| NLR | 0.59 | 0.38 | 0.27 | 0.52 | |
| p value AUC | 0.4365 | 0.3201 | 0.0028 | 0.4819 | |
| PSI | Cut off | 12 | 19.3 | 19.3 | 19.3 |
| AUC | 0.530 (0.450–0.610) | 0.538 (0.432–0.642) | 0.708 (0.561–0.829) | 0.528 (0.341–0.709) | |
| Sensitivity (%) | 57.41 | 86.11 | 80.95 | 44.44 | |
| Specificity (%) | 58.10 | 32.76 | 60.71 | 81.82 | |
| PPV (%) | 41.30 | 44.30 | 60.70 | 50.00 | |
| NPV (%) | 72.60 | 79.20 | 81.00 | 78.30 | |
| PLR | 1.37 | 1.28 | 2.06 | 2.44 | |
| NLR | 0.73 | 0.42 | 0.31 | 0.68 | |
| p value AUC | 0.5267 | 0.5284 | 0.0067 | 0.8279 | |
| SR | Cut off (1/s) | −0.98 | −0.79 | −0.75 | −0.62 |
| AUC | 0.553 (0.473–0.632) | 0.530 (0.454–0.662) | 0.645 (0.496–0.777) | 0.533 (0.346–0.713) | |
| Sensitivity (%) | 83.33 | 66.67 | 66.67 | 33.34 | |
| Specificity (%) | 31.43 | 48.28 | 60.71 | 86.36 | |
| PPV (%) | 38.50 | 44.40 | 56.00 | 50.00 | |
| NPV (%) | 78.60 | 70.00 | 70.80 | 76.00 | |
| PLR | 1.22 | 1.29 | 1.70 | 2.44 | |
| NLR | 0.53 | 0.69 | 0.55 | 0.77 | |
| p value AUC | 0.2497 | 0.6162 | 0.0767 | 0.7970 |
Parenthesis shows 95% confidence interval.
PPV positive predictive value, NPV negative predictive value, PLR positive likelihood ratio, NLR negative likelihood ratio.
4. Discussion
Strain imaging with 2D-STE, besides unearthing the hidden LV dysfunction, is also found to be associated with the severity of CAD. In patients with acute chest pain in an emergency, Lee et al found that longitudinal strain predicted CAD with high sensitivity and specificity.23 In a small study of 64 patients suspected of NSTEACS, Dahlslett et al found that GLS had a sensitivity and specificity of 93% and 78%, respectively, in excluding patients with insignificant CAD.24 Apart from the diagnosis of CAD, GLS has also been found to predict the severity of CAD in NSTEACS patients in some studies. Zhang et al, in a study of 139 patients suspected of NSTEACS, found that the endocardial GLS demonstrated better diagnostic accuracy than other strain parameters for identifying complex CAD.25 In a similar study by Tibaldi et al, a GLS of < -16.5, had sensitivity and specificity of 96% and 88% respectively for the detection of severe coronary obstructions.26 These were in concordance to our study where GLS had 85.71% sensitivity and 53.57% specificity with a cut-off value of −11.2% for detecting LM or TVD. The strain parameters also correlated significantly with the syntax score.
Another novel strain parameter, post systolic shortening, was studied by Brainin et al, in which they found that it predicted an increased risk of major adverse cardiovascular events (MACE) and death in the general population.19 Post-systolic shortening has also been an indicator of significant CAD in patients with stable angina and offers novel prognostic information regarding the risk of future cardiovascular events.27 But till today, a study has yet to be done to assess PSS in NSTEACS patients. In our research, PSI could detect LM or TVD with 80% sensitivity and 60% specificity at a cut-off value of 19.3%. PSI also was strongly correlated with syntax scores. To the best of our knowledge, this is the first study to measure PSI in NSTEACS patients.
Strain rate is not studied extensively in patients with NSTEACS. Hoshi et al, in a study of 50 NSTEACS patients, could not find a significant difference in strain rate between those with LM ± TVD and others.28 In a study of 80 consecutive ACS patients by Shenouda et al, the mean regional systolic strain rate accurately predicted the culprit lesion.29 Although in our study, the diagnostic accuracy was low [AUC 0.645 (CI 0.496 to 0.777); P = 0.07], the systolic strain rate was significantly different between group A and group B and correlated significantly with the syntax score.
5. Limitations
Although our study showed significant correlation of strain parameters with severity of CAD, there were some limitations. This was a single-centred study with limited sample size. A multicentre study with a larger sample volume would make the study strong. We have not studied territorial strain which has been found to identify culprit vessel. Inclusion of territorial strain would have made the results better. Strain parameters may be confounded by hypertension, diabetes, dyslipidaemia, or drugs.
6. Conclusion
To the best of our knowledge, this is the first study to evaluate GLS, PSS, PSI, and SR in patients with NSTEACS. We found a significant correlation between strain parameters and the angiographic severity of CAD. Among the strain parameters, GLS was found to be most accurate for detecting severe CAD. Since it was a single centre study, a multicentre study involving a larger population is required for better generalization.
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Footnotes
Supplementary data to this article can be found online at https://doi.org/10.1016/j.ihj.2023.09.003.
Appendix A. Supplementary data
The following is the Supplementary data to this article:
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